fluvoxamine and Depressive-Disorder

RDoC conceptualises psychopathology as neurobiologically-rooted behavioural psychological "constructs" that span dimensionally from normality to pathology, but its clinical utility remains controversial.. To explore RDoC's potential clinical utility by examining antidepressant effectiveness through Negative Valence Systems (NVS) domain constructs.. A systematic review was conducted on Web of Science, MEDLINE, EMBASE and PsycINFO for antidepressant trials that included psychometric instruments assessed by Watson, Stanton & Clark (2017) to represent NVS constructs of Acute Threat, Potential Threat and Loss.. 221 citations were identified; 13 were included in qualitative synthesis, none for quantitative analysis. All suffered from significant bias risks. 9 antidepressants were investigated, most within 1 construct, and most were found to be effective. Paroxetine, citalopram and fluvoxamine were found to be effective for Acute Threat, fluoxetine, desvenlafaxine and sertraline for Potential Threat, and sertraline, fluvoxamine, fluoxetine and desvenlafaxine effective for Loss. Nefazodone was found to be ineffective for acute fear.. Preliminary evidence supports RDoC NVS constructs' clinical utility in assessing antidepressant effectiveness, but lack of discriminant validity between Potential Threat and Loss supports their recombination into a single Distress construct. Finding of effectiveness within "normal" construct levels support the utility of a dimensional approach. Testable hypotheses were generated that can further test RDoC's clinical utility.

Topics: Algorithms; Antidepressive Agents; Citalopram; Clinical Trials as Topic; Depressive Disorder; Desvenlafaxine Succinate; Fluoxetine; Fluvoxamine; Humans; Paroxetine; Psychometrics; Sertraline; Treatment Outcome

The four Ds of medical malpractice are duty, dereliction (negligence or deviation from the standard of care), damages, and direct cause. Each of these four elements must be proved to have been present, based on a preponderance of the evidence, for malpractice to be found. The principles of psychopharmacology and the information in the package insert for a drug often play a central role in deciding whether dereliction and direct cause for damages were or were not applicable in a particular case. The author uses data from two cases in which patients were inadvertently fatally poisoned by medication to illustrate two ways in which such information can affect the outcome. In one case, the clinician should have known that he was giving a toxic dose to the patient, whereas that was not true in the other case.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Child; Depressive Disorder; Desipramine; Fatal Outcome; Female; Fluvoxamine; Forensic Psychiatry; Humans; Imipramine; Male; Malpractice; Mental Disorders; Psychopharmacology; Schizophrenia; Thioridazine

New-generation antidepressants are a heterogeneous class of drugs used in the treatment of depression and related disorders. This review deals with the first new-generation antidepressant class to enter the pharmaceutical market, i.e., selective serotonin reuptake inhibitors (SSRIs), which are still the most prescribed and widely used ones. Their common characteristics are the comparable clinical efficacy, good tolerability and relative safety in comparison to "first generation antidepressants", i.e. classic tricyclic antidepressants and monoamine oxidase inhibitors. This class of drugs includes fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine and, since 2011, vilazodone. In this review, the main pharmacodynamic and pharmacokinetic properties of the six commercially available SSRIs are described, focusing on side and toxic effects, chemical-clinical correlations, interactions with other drugs, the role of therapeutic drug monitoring (TDM) and related bioanalytical methodologies.

Topics: Benzofurans; Citalopram; Depressive Disorder; Drug Monitoring; Fluoxetine; Fluvoxamine; Humans; Indoles; Paroxetine; Piperazines; Selective Serotonin Reuptake Inhibitors; Sertraline; Vilazodone Hydrochloride

Cognitive impairment is a primary feature of patients with major depressive disorder (MDD) and is characterised by stress-induced neural atrophy. Via alpha-adrenergic, anti-cholinergic and anti-histaminic activities, several antidepressants can cause significant counter-therapeutic cognitive impairment. Evidence is emerging of the involvement of sigma-1 receptor agonism in the mechanism of action of some antidepressants, notably fluvoxamine. Sigma-1 receptors are abundant in areas affected by depression/stress-induced cerebral atrophy and their ligands have a unique pharmacological profile; they may promote neurogenesis and initiate adaptive neural plasticity as a protection/reaction to stress. Fluvoxamine, as a potent sigma-1 receptor agonist, has shown ameliorating effects in animal models of psychosis, depression, stress, anxiety, obsessive-compulsive disorder (OCD) and aggression and has been shown to improve cognitive impairments. In humans, fluvoxamine may repair central nervous system (CNS) atrophy and restore cognitive function. The current review explores the mechanisms through which sigma-1 receptors can modulate cognitive function and examines how antidepressant therapy with fluvoxamine may help improve cognitive outcomes in patients with depression.

Topics: Animals; Cognition; Cognition Disorders; Depressive Disorder; Fluvoxamine; Humans; Receptors, sigma; Sigma-1 Receptor; Treatment Outcome

Methylphenidate and other psychostimulants have received substantial attention for the management of depression in patients with medical co-morbidities as well as for the symptomatic palliation of various neuropsychiatric disorders. Despite having been of little use in the first-line treatment of depressive disorders, some evidence does suggest that they may be of potential benefit as an antidepressant augmentation strategy in patients who fail to respond to stand-alone antidepressant regimens. However, such claims appear to be based entirely on case reports and to date, no appropriate placebo-controlled studies have been carried out on healthy young subjects. We report a case of a woman with refractory depression who successfully responded to methylphenidate augmentation of fluvoxamine. Her clinical picture was dominated by significant biological symptoms, which included apathy, anergia, increased appetite, and somnolence, with marked secondary functional impairment. Several antidepressant treatment modalities were attempted, including electroconvulsive therapy, with little improvement in her symptomatology. Augmentation of fluvoxamine with methylphenidate ultimately brought about a rapid and sustained complete remission of her depression. We will highlight how methylphenidate and other psychostimulants, when used with caution and an appreciation of their potential risk for abuse, may prove to be remarkably effective agents for antidepressant augmentation, including that of partially-effective or ineffective selective serotonin re-uptake inhibitors. Evidence for such use of methylphenidate unfortunately remains largely empirical and adequate placebo-controlled studies are therefore required to support or refute this claim.

Topics: Adult; Antidepressive Agents, Second-Generation; Central Nervous System Stimulants; Depressive Disorder; Diagnosis, Differential; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Methylphenidate

Selective serotonin [5-hydroxytryptamine (5-HT)] reuptake inhibitors (SSRIs) and the 5-HT noradrenaline reuptake inhibitor, venlafaxine, are mainstays in treatment for depression. The highly specific actions of SSRIs of enhancing serotonergic neurotransmission appears to explain their benefit, while lack of direct actions on other neurotransmitter systems is responsible for their superior safety profile compared with tricyclic antidepressants. Although SSRIs (and venlafaxine) have similar adverse effects, certain differences are emerging. Fluvoxamine may have fewer effects on sexual dysfunction and sleep pattern. SSRIs have a cardiovascular safety profile superior to that of tricyclic antidepressants for patients with cardiovascular disease; fluvoxamine is safe in patients with cardiovascular disease and in the elderly. A discontinuation syndrome may develop upon abrupt SSRI cessation. SSRIs are more tolerable than tricyclic antidepressants in overdose, and there is no conclusive evidence to suggest that they are associated with an increased risk of suicide. Although the literature suggests that there are no clinically significant differences in efficacy amongst SSRIs, treatment decisions need to be based on considerations such as patient acceptability, response history and toxicity.

Topics: Antidepressive Agents, Second-Generation; Body Weight; Central Nervous System Diseases; Depressive Disorder; Fluvoxamine; Humans; Selective Serotonin Reuptake Inhibitors; Sexual Dysfunction, Physiological; Sleep Wake Disorders

Some behavioral side effects of selective serotonin reuptake inhibitor (SSRI) antidepressants have been known for a long time. Since the introduction of these drugs in the 1990s, publications have regularly reported behavioral side effects in children and adolescents, including excitation, motor restlessness, social disinhibition, and above all self-injurious ideation and behavior. Clinical trials provide only limited data. Although these data suggest that some self-injurious and suicidal behavior may indeed occur in children and adolescents receiving SSRIs, they are too disparate to specify the frequency of these acts. Clinical trials provide useful data about drug efficacy, but their methodology is inappropriate for determining the frequency of such side effects. SSRI and suicidality: the data are difficult to read. Although some epidemiologic data suggest that SSRIs may increase the risk of occurrence of self-injurious and suicidal behavior in children and adolescents, other epidemiologic data show that the rate of suicide mortality in children and adolescents has decreased since the introduction of SSRIs. No known mechanism explains how SSRIs might increase the risk of these behavioral side effects. It is clear, however, that these effects are not particular to children and adolescents but may also be observed among adults. SSRIs must be used rationally and carefully in children and adolescents. They should not be administered routinely in youth with obsessive-compulsive or depressive disorders. Their use should be reserved for severe disorders or when psychotherapy alone has been shown to be inadequate, and when they are used, efficacy and side effects must be monitored carefully and frequently.

Topics: Adolescent; Adult; Age Factors; Antidepressive Agents, Second-Generation; Case-Control Studies; Child, Preschool; Citalopram; Confidence Intervals; Depressive Disorder; Family Practice; Female; Fluoxetine; Fluvoxamine; History, Medieval; Humans; Male; Obsessive-Compulsive Disorder; Paroxetine; Placebos; Psychotherapy; Randomized Controlled Trials as Topic; Risk; Safety; Selective Serotonin Reuptake Inhibitors; Self-Injurious Behavior; Sertraline; Suicide; Suicide, Attempted

Mice fed a thiamine deficient (TD) diet, showed some abnormal behaviors such as amnesia and mood abnormality. It is known that several neurons, especially marked in serotonergic neuron, are damaged in humans and rodents in the earlier phase of TD. The symptoms derived from dysfunction of serotonergic neurons are observed in Wernicke-Korsakoff patients (WKS)-derived TD, and it is known that fluvoxamine is effective for WKS. However, the mechanism of this dysfunction is still unclear. For that reason, we studied the relative mechanism between abnormal behaviors and selective dysfunction of serotonergic neurons in TD animals. As a result, this dysfunction by TD is much affected by the brainstem region. But the effect of fluvoxamine on depressive symptoms in WKS patients is not reported; therefore we also studied the effects of fluvoxamine on the depressive behaviors in TD mice as a model of WKS. The increase of immobility time in a forced swimming test as depressive behavior in TD mice was significantly inhibited by fluvoxamine, suggesting an improvable effect on depressive symptoms. With those results of ours, the possible mechanisms between the abnormal behaviors derived from the dysfunction of serotonergic neurons and the role of serotonin in TD and WKS are reviewed here.

Topics: Animals; Depressive Disorder; Fluvoxamine; Humans; Korsakoff Syndrome; Mice; Selective Serotonin Reuptake Inhibitors; Serotonin; Thiamine Deficiency

The response of patients to drugs can be affected by genetic polymorphisms/defects in drug metabolizing enzymes, transporters, and receptors. Genetic polymorphisms/defects are generated by mutation of coding regions and/or noncoding regions of target genes, such as single-point mutations, deletions/insertions, variation in the number of tandem repeats, etc. If a genetic defect in a patient which affects drug response were known, it would be possible to optimize medications individually. The author developed two improved methods for detecting CYP2C19(*)2 and CYP2C19(*)3. Using the methods, the type of CYP2C19 gene was examined in 80 inpatients, and the medication status of patients with the mutation was examined focusing on dosage and side effects. The author also examined polymorphisms of the serotonin transporter/biosynthetic or metabolizing enzymes in depressive patients treated with fluvoxamine, a selective serotonin reuptake inhibitor, and the relationship between clinical efficacy and polymorphisms was investigated. As a result, patients with the S/S genotype of 5-HTTLPR were found to experience better clinical efficacy.

Topics: Adolescent; Adult; Aged; Aryl Hydrocarbon Hydroxylases; Carrier Proteins; Cytochrome P-450 CYP2C19; Depressive Disorder; Female; Fluvoxamine; Genotype; Humans; Male; Membrane Glycoproteins; Membrane Transport Proteins; Mixed Function Oxygenases; Mutation; Nerve Tissue Proteins; Pharmacogenetics; Polymorphism, Genetic; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins

Topics: Antidepressive Agents, Second-Generation; Depressive Disorder; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Disease Progression; Drug Therapy, Combination; Fluvoxamine; Humans; Lithium; Male; Middle Aged; Psychotherapy; Reference Standards; Selective Serotonin Reuptake Inhibitors

Serotonergic and adrenergic enhancement may be synergistic and more effective than serotonergic enhancement alone in treating depression. The dual serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine is a dual reuptake inhibitor that may therefore offer greater efficacy than selective serotonin reuptake inhibitors (SSRIs).. Data from eight randomized, double-blind, controlled studies were pooled to compare efficacy in depressed patients receiving venlafaxine/venlafaxine extended release (XR), SSRIs, or placebo for

Topics: Adult; Anti-Anxiety Agents; Antidepressive Agents, Second-Generation; Clinical Trials as Topic; Cyclohexanols; Depressive Disorder; Double-Blind Method; Female; Fluoxetine; Fluvoxamine; Humans; Male; Paroxetine; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Time Factors; Venlafaxine Hydrochloride

Child and adolescent depression is one of the greatest health concerns in our society today. This article critically reviews the literature on the psychopharmacologic treatment of adolescent depression. Although double-blind studies have failed to show the efficacy of tricyclic antidepressants, more recent evidence has emerged for the use of selective serotonin reuptake inhibitors in this population. However, placebo-controlled, double-blind studies are limited, and many of the other newer antidepressants have yet to be investigated in treating adolescent depression. Nonetheless, antidepressants are widely prescribed to these populations, and psychiatric nurses are actively involved in assessing and monitoring the need for these medications in adolescents.

Topics: Adolescent; Child; Cyclohexanols; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline; Venlafaxine Hydrochloride

Newer antidepressants are more expensive in terms of acquisition costs than older drugs. However, cost effectiveness simulations and retrospective analyses of administrative databases of newer antidepressants, including venlafaxine, suggest that the higher acquisition costs may be offset or more than offset by savings of other treatment costs. Because simulations and retrospective studies are vulnerable to multiple methodologic uncertainties, large scale randomized "real-world" cost effectiveness experiments are needed. If venlafaxine in actual practice is more effective or has a more rapid onset of action than SSRIs as suggested by efficacy studies and existing meta-analyses, these effects could translate into pharmacoeconomic advantages.

Topics: Antidepressive Agents, Second-Generation; Buspirone; Clinical Trials as Topic; Cost-Benefit Analysis; Cyclohexanols; Depressive Disorder; Drug Tolerance; Fluoxetine; Fluvoxamine; Humans; Sertraline; Treatment Outcome; Venlafaxine Hydrochloride

Seven of the newest antidepressants are the serotonin selective reuptake inhibitors (fluoxetine, sertraline, paroxetine, and fluvoxamine [currently approved in the United States for obsessive-compulsive disorder only]), a serotonin norepinephrine reuptake inhibitor (venlafaxine), a postsynaptic serotonin antagonist/presynaptic serotonin reuptake inhibitor (nefazodone), and presynaptic/postsynaptic noradrenergic/serotonergic receptor antagonist (mirtazapine). Many of these drugs are potent inhibitors of the cytochrome P450 (CYP) enzymes of the liver. The CYP enzymes most relevant to the use of antidepressants and for which the most thorough data are available are the CYP1A2, CYP2D6, and CYP3A4. These 3 CYP isoenzymes are discussed in relation to some of the drugs they metabolize, and appropriate cautions are recommended for concurrent administration of these new antidepressants and other drugs frequently prescribed to elderly patients.

Topics: Antidepressive Agents; Cyclohexanols; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Depressive Disorder; Drug Interactions; Drug Therapy, Combination; Fluoxetine; Fluvoxamine; Humans; Mixed Function Oxygenases; Piperazines; Selective Serotonin Reuptake Inhibitors; Triazoles; Venlafaxine Hydrochloride

Fluvoxamine, a serotonin selective reuptake inhibitor, has been available as an antiobsessional agent in the United States since 1995. However, it has been utilized as an effective antidepressant for many years in various European countries. The controlled trials of fluvoxamine in the pharmacotherapy of depression are reviewed. The drug compares well with a variety of other antidepressants. It appears safe and well tolerated in daily doses of 50 to 300 mg. The most common adverse events are gastrointestinal complaints, particularly nausea. Initiating pharmacotherapy at lower doses and increasing over the period of 1 to 2 weeks minimizes this discomfort.

Topics: Antidepressive Agents; Controlled Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Drug Administration Schedule; Fluvoxamine; Humans; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome

The disposition characteristics and pharmacokinetic parameters of drugs provide fundamental data for designing safe and effective dosage regimens. A drug's volume of distribution, clearance, and the derived parameter, half-life, are particularly important, as they determine the degree of fluctuation between a maximum and minimum plasma concentration during a dosage interval, the magnitude of the steady-state concentration, and the time to reach a steady-state plasma concentration upon chronic dosing. Potential drug-drug interactions can be predicted with knowledge of affinities for various cytochrome P450 (CYP) isozymes.. The literature was searched for information related to the pharmacokinetic properties of fluvoxamine and reports of its involvement in drug interactions.. The primary pharmacokinetic variables for fluvoxamine have been estimated in single and multiple dose studies in animals, health volunteers, and patients. Fluvoxamine is well absorbed after oral administration, widely distributed in the body, and eliminated with a mean half-life of 15 hours and a range from 9 hours to 28 hours. Its disposition is altered in hepatic, but not renal, disease. Data from elderly subjects reflect a modest need for dosage adjustment in this population. Fluvoxamine produces no active metabolites. The specific cytochrome isozymes involved in the hepatic elimination of the drug are undefined. Data from studies relating the plasma concentration of fluvoxamine to its clinical effects do not support routine plasma concentration monitoring in depression or anxiety disorders. Fluvoxamine has prominent affinity for the CYP12 isozyme, lesser affinity for the CYP3A4 and CYP2C isozymes, and minimal affinity for CYP2D6. This profile suggests the need for careful dosage adjustment when used together with some drugs that have a narrow therapeutic range in order to minimize inhibiting their metabolism.. Overall, the pharmacokinetic profile of fluvoxamine is adequately defined to provide guidelines for developing safe and effective dosage regimens for most types of patients.

Topics: Adolescent; Adult; Age Factors; Aged; Animals; Anxiety Disorders; Biological Availability; Cytochrome P-450 Enzyme System; Depressive Disorder; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Female; Fluvoxamine; Half-Life; Humans; Intestinal Absorption; Male; Middle Aged; Protein Binding; Sex Factors; Tissue Distribution

The treatment of depression can be problematic in the elderly patient. The advent of the serotonin selective reuptake inhibitors (SSRIs) represents a significant advance in the treatment of depression. Sufficient data from controlled studies now exist on the efficacy and safety of these agents in geriatric patients to recommend them as a primary treatment for major depressive disorder. SSRIs appear to have significant advantages over older drugs, especially tricyclic agents, in this age group. The lack of significant anticholinergic and antihistaminergic side effects results in better tolerability and better compliance. While SSRIs are not free of side effects, those that occur can usually be managed in the context of continued treatment of the depressive episode. This article reviews data from controlled studies of the treatment of geriatric depression for all four available SSRIs in the United States-fluoxetine, sertraline, paroxetine, and fluvoxamine (which is approved in the United States for treating only obsessive-compulsive disorder). Differences among the SSRIs are examined, particularly with reference to clinically relevant differences in pharmacokinetics and hepatic isoenzyme inhibition. Principles of clinical management are discussed, including dose initiation and titration, side effect management, augmentation and combinations, and length of treatment. Finally, the use of SSRIs in special elderly populations is discussed.

Topics: 1-Naphthylamine; Age Factors; Aged; Controlled Clinical Trials as Topic; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

To review the case reports and case series of movement disorders ascribed to the use of serotonin selective reuptake inhibitors (SSRIs).. Reports of SSRI-induced extrapyramidal symptoms (EPS) in the literature were located using a MEDLINE search and review of bibliographies.. Among the 71 cases of SSRI-induced EPS reported in the literature, the most common side effect was akathisia (45.1%), followed by dystonia (28.2%), parkinsonism (14.1%), and tardive dyskinesia-like states (11.3%). Among patients with Parkinson's disease treated with SSRIs, there were 16 cases of worsening parkinsonism. Patients who developed dystonia, parkinsonism, or tardive dyskinesia were older on average than patients with akathisia; 67.6% of affected patients were females. Fluoxetine, the most commonly prescribed SSRI to date, was implicated in 53 (74.6%) of cases of SSRI-induced EPS. Several reports (57.7%) were confounded by the concomitant use of other medications that can contribute to the development of EPS.. SSRI-induced EPS are probably related to agonism of serotonergic input to dopaminergic pathways within the CNS. Several patient-dependent and pharmacokinetic variables may determine the likelihood that EPS will emerge. Although these side effects are infrequent, clinicians should be alert to the possibility of their occurrence.

Topics: 1-Naphthylamine; Adult; Age Factors; Aged; Akathisia, Drug-Induced; Depressive Disorder; Dyskinesia, Drug-Induced; Dystonia; Female; Fluoxetine; Fluvoxamine; Humans; Male; MEDLINE; Middle Aged; Parkinson Disease, Secondary; Paroxetine; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Sertraline; Sex Factors; United States

Topics: Antidepressive Agents; Antidepressive Agents, Second-Generation; Depressive Disorder; Fluvoxamine; Humans; Piperazines; Triazoles

The presently available selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, despite their common mechanism of action, differ in their chemical structure, metabolism and pharmacokinetics. From a clinical point of view, it is of relevance that potency to inhibit the cytochrome P450 isozyme CYP2D6 gradually decreases from paroxetine, fluoxetine, norfluoxetine, desmethylcitalopram, fluvoxamine, and sertraline down to citalopram, explaining to a great extent differences in pharmacokinetic interactions between the SSRIs and tricyclic antidepressants, which are metabolized by this enzyme. Fluvoxamine interacts with these drugs by a mechanism involving inhibition of CYP1A2, CYP3A4, and CYP2C19. Except for paroxetine, a substrate of CYP2D6, little is known about the enzymes implicated in the metabolism of SSRIs. Fluoxetine and citalopram are used as racemic drugs. Data on the stereoselectivity of their enantiomers in the inhibition of serotonin (5-HT) uptake in the animal brain, also those available on their metabolism and kinetics in humans, are presented. It may be concluded that for routine therapeutic drug monitoring, the plasma level measurement of the enantiomers of citalopram and fluoxetine is probably of little relevance. However, for the study of the structure-activity relationship between these drugs and the cerebral 5-HT transporter, the stereochemical differences of these enantiomers should be considered. In this sense, the enantiomers of these drugs could represent a promising tool to increase present knowledge.

Topics: 1-Naphthylamine; Animals; Citalopram; Cytochrome P-450 Enzyme System; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline; Stereoisomerism

The tricyclic antidepressants (TCAs) are still considered as first-line treatment for depression, despite the availability of the selective serotonin reuptake inhibitors (SSRIs). This paper considers the current situation in reverse by assuming that only the SSRIs, in particular fluvoxamine, are available and the TCAs (amitriptyline, imipramine, clomipramine and dothiepin) are the potential "new" drugs. The criteria for an "ideal" antidepressant are discussed and the efficacy, safety and cost-effectiveness of these agents are compared.

Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Binding Sites; Cost-Benefit Analysis; Depressive Disorder; Fluvoxamine; Humans; Imipramine; Selective Serotonin Reuptake Inhibitors

The need to subtype patients with affective disorders on the basis of biological characteristics is well recognized, and much of the research in this area has focused on the serotonergic system. Biological subtyping can be approached using both peripheral and central markers. Peripheral markers include platelet serotonin concentrations, the density and affinity of platelet serotonin reuptake and platelet 5-HT2 receptors, and plasma serotonin concentrations. Central markers include cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations, and endocrine, psychological and body temperature responses to challenge tests with a number of serotonergic drugs. More recently, the role of selective serotonin reuptake inhibitors (SSRIs) and other serotonergic drugs in sleep, and in the control of cardiovascular homeostasis, has been studied. This may provide a greater understanding of the mechanisms of serotonin dysregulation in affective disorders, and may ultimately improve treatment of these conditions.

Topics: Biomarkers; Blood Pressure; Depressive Disorder; Fluvoxamine; Heart Rate; Humans; Lithium; Lofepramine; Mood Disorders; Selective Serotonin Reuptake Inhibitors; Sleep Wake Disorders; Time Factors

To review the respective pharmacologic profiles of the selective serotonin reuptake inhibitors (SSRIs), with particular emphasis placed on clinically relevant distinctions.. A MEDLINE search was conducted to identify English language literature published within the last five years on the four SSRIs (fluoxetine, sertraline, paroxetine, fluvoxamine). Previous review articles were scrutinized for additional citations, and manufacturers provided a contemporary bibliography of more recent material.. Studies were selected for specific citation on the basis of comparative research merit and the contribution of this original literature to the pharmacologic profile(s) described.. All SSRIs appear to be more efficacious than placebo for the acute treatment of major depressive disorder (MDD). Short-term (six-week) efficacy was comparable with that of tricyclic antidepressants for the amelioration of MDD regarded as moderate in severity. Further comparative trials are clearly indicated to demonstrate the therapeutic benefits of SSRIs in specific populations (e.g., geriatric, severely ill) and to demonstrate sustained benefit with long-term prophylaxis. Other potential indications for SSRIs include obsessive-compulsive disorder, panic disorder, bulimia, and chronic pain syndromes. Pharmacokinetic profiles of the four SSRIs reveal similar parametric values, and most quantitative differences are of limited clinical significance. Adverse effects are common but ordinarily mild and transient, primarily restricted to the gastrointestinal tract and central nervous system. Important differences in the prevalence or severity of these adverse effects await the accumulation of further clinical experience and the completion of additional comparative trials. Similarly, the relative propensity of SSRIs to inhibit the metabolism of other medications is currently under investigation.. The four SSRIs studied appear to be more similar than they are different. Slowly, important distinctions are beginning to emerge with regard to adverse effect profiles and potential drug interactions. Given that the costs of these respective medications are comparable, such differences may ultimately serve to establish the preferential selection of individual agents in specific clinical situations.

Topics: 1-Naphthylamine; Alcoholism; Antidepressive Agents; Anxiety Disorders; Clinical Trials as Topic; Depressive Disorder; Drug Interactions; Fluoxetine; Fluvoxamine; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline

Fluvoxamine, a selective serotonin reuptake inhibitor, was studied extensively in 34,587 predominantly depressed patients in 66 studies conducted world-wide. These studies were largely uncontrolled trials representing the use of fluvoxamine by psychiatric and general practice physicians in everyday conditions. The safety data were analyzed according to standardized medical review and data management policies. Approximately 70% of the fluvoxamine population were female and 44% were aged 31-51 years. The modal total daily dose was 100 mg. Safety findings revealed a pharmacological adverse event profile similar to that seen with other serotonin reuptake inhibitors. Nausea was found to be the only common symptom, with an incidence rate of 16%. Approximately 2% of the fluvoxamine population reported at least one serious adverse event (per FDA criteria). Overall suicidality rates of fluvoxamine were found to be low (0.7%). No cases of zimelidine syndrome, bleeding syndrome or Guillain-Barré syndrome were identified. Overall, fluvoxamine was found to be safe and well tolerated suggesting a favorable alternative in the treatment of depression.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Middle Aged; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Fluvoxamine facilitates serotoninergic neurotransmission via potent and selective inhibition of serotonin (5-hydroxytryptamine; 5-HT) reuptake into presynaptic neurones. The overall antidepressant efficacy of fluvoxamine 100 to 300 mg/day for 4 to 6 weeks in once daily or divided dosage regimens appears to be at least comparable to that of imipramine and similar to that of clomipramine, dothiepin, desipramine, amitriptyline, lofepramine, maprotiline, mianserin and moclobemide. The efficacy of fluvoxamine has been maintained for up to 1 year, but long term data are limited, and there are no comparative studies of fluvoxamine with other selective serotonin reuptake inhibitors. In some studies, fluvoxamine appeared to have an earlier beneficial effect on suicidal ideation and/or anxiety or somatic complaints compared with imipramine, dothiepin and maprotiline. Gastrointestinal adverse effects, especially nausea, are commonly reported with fluvoxamine but are generally mild to moderate in severity. The tolerability profile of fluvoxamine appears to be more favourable than that of tricyclic antidepressants in terms of cardiotoxic and anticholinergic adverse effects, sedation, weight gain and death from overdosage. Thus, fluvoxamine is an effective and well tolerated antidepressant agent that is becoming established as an alternative to older agents in patients with mild, moderate or severe depression. Fluvoxamine may be particularly beneficial in potentially suicidal patients with severe depression, in those with an underlying compulsive personality or cardiovascular disorder, in patients with coexistent anxiety or agitation, and in the elderly.

Topics: Animals; Clinical Trials as Topic; Depression; Depressive Disorder; Fluvoxamine; Humans

The therapeutic efficacy of fluvoxamine has been demonstrated in large numbers of patients participating in comparative double-blind placebo-controlled studies using imipramine as the active reference compound. Overall, patients treated with fluvoxamine for 4 to 6 weeks had significant amelioration of their depression compared with placebo-treated patients. More importantly, the response rate in patients with severe depression was greater than in patients with mild or moderate depression. However, several investigators have observed high placebo response rates, and in some studies there has been a similar response rate to imipramine and placebo treatment. While the high placebo response rate may have resulted from methodological problems, the issue does raise some questions that can only be resolved by further investigation.

Topics: Clinical Trials as Topic; Depressive Disorder; Fluvoxamine; Humans; Neurotransmitter Uptake Inhibitors; Psychiatric Status Rating Scales; Serotonin

A review of the safety and tolerability of fluvoxamine in worldwide marketing studies involving 24,624 patients, predominantly receiving fluvoxamine treatment in uncontrolled studies in depression, has been conducted. There was a marked preponderance of female patients and patients aged between 30 and 50 years. The majority of patients were treated for 6 weeks, with the most frequent modal total daily dose being 100mg. The greatest proportion of adverse experiences occurring, by COSTART body system, affected the digestive system (24.1%), the nervous system (23.7%), and the body as a whole (15.3%). The only adverse experience with an incidence greater than 10% was nausea (15.7%), with somnolence (6.9%) and asthenia (6.2%) as the next most frequent experiences. Notably, the rates of agitation and anxiety were only 1.4 and 1.3%, respectively. The incidences of adverse experiences increased with age, and were slightly higher in females than males. 15.1% of patients discontinued treatment prematurely as a result of adverse experiences, principally nausea, dizziness, vomiting, somnolence, abdominal pain, and headache. The overall incidence of serious adverse events associated with fluvoxamine treatment was 2.5%, and the incidence of overall suicidality, including suicidal ideation, overdose, and intentional overdose as well as attempted and completed acts of suicide, was remarkably low at 0.8%.

Topics: Adolescent; Adult; Aged; Databases, Factual; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Middle Aged; Product Surveillance, Postmarketing

The pharmacology and pharmacokinetics, adverse effects, drug interactions, efficacy, and dosage and administration of the new selective serotonin reuptake inhibitors paroxetine, sertraline, and fluvoxamine are reviewed. Paroxetine, sertraline, and fluvoxamine all have large volumes of distribution and are highly bound to plasma proteins. In contrast to fluoxetine, these three drugs possess shorter elimination half-lives of approximately one day and are metabolized to clinically inactive compounds. Nausea was the most commonly reported adverse effect for all three agents. Other reported adverse effects are headache, sedation, dry mouth, insomnia, sexual dysfunction, and constipation. Because of their favorable pharmacokinetic profiles, paroxetine, sertraline, and fluvoxaetine are less likely than fluoxamine to interact with other drugs. Paroxetine has been found to be superior to placebo and equivalent to amitriptyline, imipramine, clomipramine, and doxepin in treatment of depression. Sertraline has been found to be superior to placebo and equivalent to amitriptyline in treatment of depression. Fluvoxamine has been found to be superior to placebo and equivalent to imipramine, clomipramine, desipramine, mianserin, and maprotiline in the treatment of depression. Fluvoxamine and sertraline have been shown to be superior to placebo in the treatment of obsessive-compulsive disorder. Clinical experience has demonstrated all three drugs to be effective in treatment of depression. They may be especially useful in elderly patients, in those who cannot tolerate alternative treatments, and in those who do not respond to adequate trials of other antidepressant therapies.

Topics: 1-Naphthylamine; Depressive Disorder; Fluvoxamine; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline

Topics: 1-Naphthylamine; Behavior Therapy; Clomipramine; Combined Modality Therapy; Depressive Disorder; Fluvoxamine; Humans; Obsessive-Compulsive Disorder; Serotonin Antagonists; Sertraline

Topics: Antidepressive Agents; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Time Factors

The pharmacokinetic properties of the newer specific serotonin (5-HT) reuptake inhibitors are reviewed. Fluoxetine, paroxetine, sertraline, and fluvoxamine show kinetic characteristics similar to those of the older tricyclic antidepressants. They are well absorbed orally but exhibit an extensive first-pass extraction in the liver. They are widely distributed in body tissues and highly bound to plasma proteins. The clearance of these drugs by the body is accomplished almost entirely by hepatic metabolism. Fluoxetine and sertraline both produce a pharmacologically active metabolite, although insufficient data are available to evaluate the clinical significance of desmethylsertraline. With the exception of fluoxetine, which has an elimination half-life of 2 to 3 days, the other drugs have half-lives of about 1 day. Available data indicate that paroxetine and fluvoxamine achieve steady state within 4 to 14 days of chronic dosing, whereas for fluoxetine, and particularly norfluoxetine, steady state is not reached for weeks. The pharmacokinetics of these drugs are characterized by marked intersubject variability. Only preliminary data are available on steady-state plasma concentrations achieved during treatment and correlations to therapeutic or adverse effects.

Topics: 1-Naphthylamine; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Neurotransmitter Uptake Inhibitors; Paroxetine; Piperidines; Serotonin Antagonists; Sertraline

Paroxetine is a highly potent and selective inhibitor of serotonin reuptake, being more potent in vitro than fluoxetine, fluvoxamine, and sertraline. In contrast to the tricyclic antidepressants, paroxetine has little affinity for catecholaminergic or histaminergic systems. Paroxetine is well absorbed from the gastrointestinal tract and undergoes first-pass metabolism that is partially saturable. Unlike the metabolites of fluoxetine and sertraline, the metabolites of paroxetine are pharmacologically inactive in vivo. Steady-state paroxetine plasma concentrations are generally achieved within 4 to 14 days of commencing therapy and remain stable thereafter. The pharmacokinetics of paroxetine are also consistent with once-daily dosing. This pharmacologic and pharmacokinetic profile, taken together with extensive clinical data, indicates that paroxetine is a valuable addition to the physician's armamentarium for the treatment of depression.

Topics: 1-Naphthylamine; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; In Vitro Techniques; Neurotransmitter Uptake Inhibitors; Paroxetine; Piperidines; Serotonin Antagonists; Sertraline

The authors briefly review studies of the efficacy of potent serotonin reuptake inhibitors (SRIs) (e.g., clomipramine, fluvoxamine) in obsessive compulsive disorder (OCD) and compare the use of antidepressants in the treatment of depression and OCD. They propose an algorithm for those patients with OCD who fail to respond to an adequate trial with a potent SRI and discuss the promise and limitations of adding tryptophan, fenfluramine, lithium, buspirone, or a neuroleptic to ongoing SRI therapy. Other biological approaches (e.g., ECT, psychosurgery) are considered in terms of their narrowly defined roles in the treatment of patients with SRI-resistant OCD.

Topics: 1-Naphthylamine; Antidepressive Agents; Clomipramine; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Neurotransmitter Uptake Inhibitors; Obsessive-Compulsive Disorder; Paroxetine; Piperidines; Serotonin; Sertraline

Topics: Antidepressive Agents; Depressive Disorder; Desipramine; Drug Therapy, Combination; Fluoxetine; Fluvoxamine; Humans; Imipramine; Mianserin; Suicide

Fluvoxamine is a potent and specific 5-HT reuptake inhibitor which has been available since 1983 and is estimated to have been given to two and a half million patients since it was first investigated in patients with depression in the late 1970s. The effectiveness of fluvoxamine in depression is therefore analysed in this review, on the basis of ten years experience. Results from 10 international double-blind placebo-controlled trials, the large majority of which included a positive control (usually imipramine), have shown that fluvoxamine is as effective as the older tricyclic antidepressants and significantly more effective than placebo. In the majority of twenty direct comparative studies against other antidepressants, fluvoxamine has been found to be as effective and well-tolerated as the reference drug. Effectiveness in the elderly depressed and support for the use of fluvoxamine in tricyclic-resistant depression is discussed. Clinical trials of fluvoxamine conducted in anxiety states and obsessive-compulsive disorder, both of which commonly co-occur with depression, are reviewed, and the efficacy of fluvoxamine in the depressed obese and patients with bulimia nervosa is examined. Reports of adverse experiences, both from clinical trials and clinical practice are discussed, and the overall risk-benefit for fluvoxamine treatment in depression is critically assessed.

Topics: Depressive Disorder; Dose-Response Relationship, Drug; Fluvoxamine; Humans; Personality Inventory

5HT has been implicated in mechanisms of anxiety and depression for many years but the evidence is contradictory. Perhaps one error has been to think of 5HT as a unitary system when in reality it is highly differentiated. There has been an explosive increase in knowledge about different 5HT receptor subtypes and it has long been known that there are different anatomical subsystems. Evidence will be summarised that the different systems subserve different psychological functions and that dysfunction in the different systems results in depression, anxiety, panic and OCD in an understandable way. Much evidence is compatible with the idea that 5HT systems reduce the impact of impending or actual aversive events. Anticipation of an aversive event is associated with anxiety and this motivates avoidance behaviour--a normal adaptive response. There is evidence that this is mediated by projections of the dorsal raphe nucleus and associated 5HT2 and 5HT3 receptors. Projections of the median raphe nucleus and associated 5HT1A receptors appear to mediate resilience to aversive events once they have occurred or if they persist. When this system breaks down depression results. It will be argued that all effective antidepressants act on 5HT1A, natural mechanisms of resilience.

Topics: Anxiety Disorders; Brain; Depressive Disorder; Fluvoxamine; Humans; Life Change Events; Receptors, Serotonin; Serotonin

Depression is highly prevalent in the elderly and there are difficulties with definition and diagnosis. The signs and symptoms of depression may differ from those in younger patients since the elderly are frequently preoccupied with physical ailments and may have more agitation, insomnia and hypochondriasis. The aetiology and cause of depression and its association with psychosocial and other risk factors are discussed, with particular reference to masked depression, depressive delusional illness and 'pseudo dementia'. A range of treatments have been used in depressive patients, including psychotherapy, cognitive therapy, ECT and various drug treatments. In the elderly drugs may cause more problems than in younger patients. These can be divided into those associated with: pharmacokinetics, polypharmacy, side effects, dosage and lethality. Trials of antidepressants in the elderly are discussed and include trials with tricyclic antidepressants, monoamine oxidase inhibitors and SSRIs. Particular reference is made to a trial of fluvoxamine versus mianserin in the elderly, which demonstrated that fluvoxamine is as effective as mianserin in treating depression, and has fewer side effects.

Topics: Aged; Aged, 80 and over; Depressive Disorder; Fluvoxamine; Humans; Mianserin; Personality Tests; Risk Factors

Antidepressant drugs undoubtedly reduce much of the morbidity and mortality associated with a variety of depressive disorders. Certain types of antidepressant drugs have been shown to exert a relative advantage in the reduction of suicidal thoughts, and it is interesting that recent reports have noted an association between the prescription of some antidepressants and the development of suicidal and aggressive thoughts and behaviour. An analysis of the data from double-blind controlled trials of fluvoxamine, fluoxetine and paroxetine indicates that 5-HT uptake inhibitors exercise some protective effects on the emergence of suicidal thoughts, whereas the data from the studies with maprotiline show an increase in suicidal thoughts compared with placebo.

Topics: Antidepressive Agents; Depressive Disorder; Dose-Response Relationship, Drug; Fluoxetine; Fluvoxamine; Humans; Mianserin; Paroxetine; Piperidines; Serotonin Antagonists; Suicide; Suicide Prevention

Topics: Animals; Antidepressive Agents; Brain; Depressive Disorder; Dose-Response Relationship, Drug; Fluvoxamine; Humans; Serotonin; Serotonin Antagonists; Structure-Activity Relationship

Topics: Antidepressive Agents; Depressive Disorder; Fluvoxamine; Humans; Serotonin Antagonists

Topics: Aged; Aged, 80 and over; Antidepressive Agents; Depressive Disorder; Dothiepin; Fluvoxamine; Humans; Imipramine; Mianserin; Middle Aged; Serotonin Antagonists

Topics: Antidepressive Agents; Brain; Depressive Disorder; Fluvoxamine; Humans; Obsessive-Compulsive Disorder; Panic Disorder; Receptors, Serotonin; Serotonin Antagonists

Topics: Antidepressive Agents; Depressive Disorder; Drug Administration Schedule; Fluvoxamine; Follow-Up Studies; Humans; Serotonin Antagonists

Topics: Antidepressive Agents; Depressive Disorder; Fluvoxamine; Humans; Oximes

The development of a new class of antidepressants that have in common their ability to inhibit the reuptake of serotonin at neuronal synapses is reviewed. There is accumulating evidence that this class of medications constitutes an advance in the management of depression; these drugs appear to be effective antidepressants with a possibly lower and more acceptable incidence of adverse reactions than the tricyclic compounds. Further exploration of these potential advantages and of the usefulness of this group of compounds for other clinical syndromes is justified.

Topics: Citalopram; Clinical Trials as Topic; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Oximes; Propylamines; Serotonin Antagonists; Zimeldine

In recent years, the role of serotonin in the pathophysiology of depressive disorders has been intensively studied. These studies have been complemented by the development of newer antidepressant agents that exert specific effects on serotonin systems. This paper reviews the pharmacology of these newer compounds and contrasts it with those of the standard tricyclic antidepressants. The current status of various serotonergic agents is discussed. Results are reviewed from recent double-blind studies comparing three compounds (trazodone, fluoxetine, and fluvoxamine) to a standard tricyclic antidepressant. Relative efficacy, dropout rates, optimal dosages, and side effects are emphasized. Data from studies on trazodone and fluoxetine suggest that lower dosages may prove as effective (if not more effective) than very high dosages. Implications of these data are discussed. Side effects of fluoxetine and fluvoxamine include primarily nausea, weight loss, insomnia, and anxiety. Possible application of specific serotonin reuptake blockers in the treatment of obsessive-compulsive disorder and in the reduction of alcohol consumption is also reviewed.

Topics: Animals; Antidepressive Agents; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Oximes; Serotonin; Serotonin Antagonists; Trazodone

Depression has been associated with a disturbance in serotonin function as reflected in platelet uptake of the transmitter as well as in CSF levels of its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA). CSF 5-HIAA levels are subnormal in approximately 30% of melancholia patients. Early studies suggested that patients with a disturbed serotonin metabolism were less responsive to treatment with uptake inhibitors with a preferential action on noradrenaline neurons. Such findings encouraged the search for compounds with a selective effect on serotonin neurons. Although some classical antidepressants are potent inhibitors of serotonin uptake, they are not selective, since their metabolites, which appear to have antidepressant effects, inhibit noradrenaline uptake. The consistent findings of an increased risk for suicide in patients with low CSF 5-HIAA underlines the importance of exploring drugs that act on serotonin transmission. The biochemical effects of some serotonin uptake inhibitors and their clinical and research potential in depression are reviewed.

Topics: 5-Hydroxytryptophan; Alanine; Citalopram; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Imipramine; Oximes; Paroxetine; Piperidines; Propylamines; Serotonin; Serotonin Antagonists; Trazodone; Zimeldine

Fluvoxamine is a new antidepressant which potently and specifically inhibits neuronal reuptake of serotonin. In the absence of other major pharmacological effects it appears that its antidepressant activity stems from facilitation of serotoninergic neurotransmission as a result of reuptake inhibition. Studies suggest that fluvoxamine has overall therapeutic efficacy comparable with that of imipramine and clomipramine in depressive illness. It causes fewer anticholinergic-type and cardiovascular side effects than the tricyclic antidepressants but it is associated with a higher incidence of nausea and vomiting. Elderly patients also respond well to fluvoxamine. Studies are now required to compare fluvoxamine with other second generation antidepressants and to establish whether some types of depressive illness respond more readily to fluvoxamine than other agents. Thus, in patients with depressive illness, fluvoxamine offers a suitable alternative to tricyclic antidepressants and may be especially valuable in patients with concomitant cardiovascular disease, and those unresponsive to or unable to tolerate tricyclic antidepressants.

Topics: Animals; Antidepressive Agents; Depressive Disorder; Drug Interactions; Fluvoxamine; Humans; Kinetics; Oximes; Serotonin Antagonists

Assess the efficacy and safety of fluvoxamine, sertraline, citalopram, paroxetine, fluoxetine.. The study included 175 patients with alcohol dependence and depressive disorders. 161 had a diagnosis Alcohol Dependence Syndrome (ADS); 14 patients had a «dual diagnosis». All patients were randomized into 5 groups according to the drugs received. To assess the therapeutic efficacy of drugs, the following scales were used: visual analogue scale (VAS), Montgomery-Asberg Depression Rating Scale (MADRS), Hospital Anxiety and Depression Scale (HADS). The safety of drugs was assessed by the incidence of adverse events (AEs) or serious adverse events (SAEs).. The drugs relieve depressive disorders: fluvoxamine by the 7th day of treatment, sertraline, paroxetine, citalopram by the 14th day, fluoxetine by the 30th day of therapy. A significant decrease in the level of anxiety when taking fluvoxamine and citalopram occurs by the 7th day, when taking sertraline and paroxetine - by the 14th day, and when taking fluoxetine - by the 30th day. The presence of an anticraving effect in SSRIs is confirmed by the obtained strong and average correlation coefficients between affective disorders and craving for alcohol. The correlation analysis allowed drawing the conclusions about the close connection of presenting features of the affective disorders (depression and anxiety) and craving. The anticraving effect is more expressive in fluvoxamine, sertraline, citalopram and paroxetine. The most common adverse reactions (increased insomnia and anxiety) are observed in: fluoxetine, citalopram, sertraline, paroxetine. Fluvoxamine has the most favorable safety profile.. SSRIs can be effectively used for the treatment of depressive disorders in alcohol dependence.. Оценить эффективность и безопасность флувоксамина в сравнении с флуоксетином, циталопрамом, сертралином, пароксетином.. В исследование были включены 175 пациентов с синдромом зависимости от алкоголя и депрессивными расстройствами. 161 пациент имел диагноз «синдром зависимости от алкоголя»; 14 — «двойной диагноз». Все пациенты были рандомизированы на 5 групп в соответствии с получаемым препаратом. Для оценки терапевтической эффективности препаратов использовались шкалы визуальная аналоговая (ВАШ), оценки депрессии Монтгомери—Асберг (MADRS), госпитальная оценки тревоги и депрессии (HADS). Безопасность препаратов оценивалась по частоте развития нежелательных явлений (НЯ) или серьезных нежелательных явлений (СНЯ).. Флувоксамин купирует депрессивные расстройства к 7-му дню терапии, сертралин, пароксетин, циталопрам — к 14-му дню, флуоксетин — к 30-му дню. Достоверное снижение уровня тревоги при приеме флувоксамина и циталопрама происходит к 7-му дню, при приеме сертралина и пароксетина — к 14-му дню, а при приеме флуоксетина — к 30-му дню. Полученные сильные и средние коэффициенты корреляции между аффективными расстройствами и влечением к алкоголю подтверждают наличие антикрейвингового эффекта СИОЗС. Антикрейвинговый эффект больше выражен у флувоксамина, сертралина, циталопрама и пароксетина. Наиболее часто побочные реакции в виде усиления бессонницы и беспокойства наблюдаются (в порядке убывания) у флуоксетина, циталопрама, сертралина, пароксетина. Флувоксамин обладает наиболее благоприятным профилем безопасности.. СИОЗС могут эффективно использоваться для лечения депрессивных расстройств при алкогольной зависимости.

Topics: Alcoholism; Citalopram; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline

The results of the study of autonomic dysregulation in anxious and anxious-melancholic endogenomorphic depression of moderate severity are presented. It was examined 36 patients with recurrent depression and depression episode (ICD-10). At functional rest, the reduction of total heart rate variability (HRV) with the maintenance of the balance of activity of sympathetic, parasympathetic and suprasegmental ergotropic systems is revealed. These data indicate a decline in adaptive potential of the organism, loss of "autonomic flexibility" and the reduced tolerance to ordinary stressors with an over-reaction to them. The orthostatic test decreases the parasympathetic reactivity, hyperactivates suprasegmental ergotropic systems and reduces the rate of activity of sympathoadrenal baroreflex mechanisms. These changes are exacerbated with patient's age, duration of affective disorder and number of depressive episodes. The changes in the functioning of regulatory systems (in particular, autonomic) in depression are quite stable, but the full recovery are not observed.

Topics: Adolescent; Adult; Aged; Autonomic Nervous System; Baroreflex; Depressive Disorder; Female; Fluvoxamine; Heart Rate; Humans; Male; Middle Aged; Mood Disorders; Selective Serotonin Reuptake Inhibitors

Many OCD patients present with comorbid conditions, and major depression is one of the most frequent comorbidities observed. OCD patients with comorbid depression exhibit functional disability and poor quality of life. However, it is unclear whether depressive symptoms are predictive of treatment response, and debate remains whether they should be targeted in the treatment of comorbid patients. The current study aimed at assessing the predictive value of depression and OCD symptoms in the long term outcome of OCD treatment.. In the current study, relations between OCD and depressive symptoms were systematically investigated in a group of 121 OCD patients who received 16 sessions of behavior or cognitive therapy either alone or with fluvoxamine.. Depression (either as a continuous or categorical variable) was not predictive of treatment response in any of the treatment modalities for up to 5 years of follow-up. Changes in OCD symptoms largely predicted changes in depressive symptoms but not vice versa.. Subsequent to participation in the RCT, almost two-thirds of the participants received some form of additional treatment (either pharmacological or psychological), and as a result, it is impossible to determine interaction effects with additional treatment received after the trial.. Treatment of OCD with comorbid depression should focus on amelioration of OCD symptoms. When OCD treatment is successful, depressive symptoms are likely to ameliorate as well.

Topics: Adult; Cognitive Behavioral Therapy; Comorbidity; Depression; Depressive Disorder; Depressive Disorder, Major; Female; Fluvoxamine; Follow-Up Studies; Humans; Longitudinal Studies; Male; Middle Aged; Obsessive-Compulsive Disorder; Predictive Value of Tests; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Young Adult

Depression and anxiety frequently occur together or in extension of each other. According to a previous study in depressed inpatients, a high trait anxiety level correlated with a positive response to the diazepam test (DT) and a low trait anxiety level with a negative response to the test. The aim of this study is to investigate whether positive reaction to the DT is related to a positive response to fluvoxamine and whether a negative reaction to the test is related to positive response to imipramine. The DT was performed in 130 patients diagnosed with a depressive disorder. Following the DT, the patients were randomly assigned to double-blind treatment with either imipramine or fluvoxamine. Doses of both antidepressants were adjusted to attain predefined blood levels, and the outcome was evaluated 4 weeks after attaining these blood levels. Twenty-two patients had a positive response to the DT, whereas 108 patients had a negative response. Although a positive DT is correlated with a high level of trait anxiety, no differences in depressive symptomatology and antidepressant response were found between patients with a positive and a negative DT.

Topics: Adult; Aged; Antidepressive Agents; Anxiety; Depressive Disorder; Diazepam; Double-Blind Method; Female; Fluvoxamine; Humans; Imipramine; Inpatients; Male; Middle Aged; Netherlands; Predictive Value of Tests; Prevalence; Psychiatric Status Rating Scales; Severity of Illness Index; Time Factors; Treatment Outcome

The present study investigated the influence of gender and menopausal status on treatment response in depressed inpatients, treated with either imipramine or fluvoxamine. The patients were divided into three groups: men, premenopausal women and postmenopausal women. A multivariate analysis was performed using the difference in Hamilton score (pretreatment - post-treatment) for imipramine and fluvoxamine as dependent variable. The following independent variables were used: the baseline Hamilton score, the antidepressant used, the gender-group and the interaction between the type of antidepressant and gender. In total, 138 patients with a DSM IV diagnosis of depressive disorder were analysed. Men responded more favorably to imipramine (B = 7.12, P = 0.005). Premenopausal women had a better response rate to fluvoxamine than men (B = -8.66, P = 0.027). In depressed inpatients, men respond more favorably to imipramine than to fluvoxamine. Premenopausal women respond more frequently to fluvoxamine than men.

Topics: Adult; Aged; Antidepressive Agents; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Imipramine; Inpatients; Linear Models; Male; Menopause; Middle Aged; Netherlands; Psychiatric Status Rating Scales; Sex Factors; Single-Blind Method; Surveys and Questionnaires; Treatment Outcome; Young Adult

It is widely accepted that selective serotonin reuptake inhibitors (SSRIs) require 2 to 4 weeks of administration before improvements in emotional symptoms of depression are seen. We evaluated whether early monitoring of Hamilton Rating Scale for Depression (HAMD) scores in patients treated with the SSRI fluvoxamine could predict antidepressant response, and also assessed the relationship between the onset of clinical response following the start of fluvoxamine administration and its plasma concentration. Twelve depressed patients (baseline HAMD score ≥15) received an initial dose of fluvoxamine (50 mg/d) followed by an optimized maintenance dose according to their clinical symptoms after 7 d. HAMD scores and plasma drug concentrations were determined at 7 and 28 d after the first administration. There were 7 responders and 5 non-responders on day 28, as evaluated by HAMD scores. The HAMD score for the responders was significantly lower than that for the non-responders on day 7 (mean±S.D., 11.6±6.1 vs. 26.6±6.5, p=0.006). Thus, the reduction in HAMD score on day 7 was clearly divided between responders and non-responders. On day 28, the plasma concentration of fluvoxamine in responders was lower than that in non-responders (14.2±10.5 ng/ml vs. 44.2±28.1 ng/ml, p=0.051). Furthermore, receiver operating characteristic curve analysis conducted on day 28 revealed an upper concentration threshold of 28.2 ng/ml (p=0.042), with none in the responder group above that level. Our results suggest that HAMD score after the first week of treatment with fluvoxamine and the upper threshold of plasma drug concentration could predict whether a patient is a non-responder.

Topics: Adult; Antidepressive Agents; Anxiety Disorders; Depressive Disorder; Feeding and Eating Disorders; Female; Fluvoxamine; Humans; Japan; Male; Middle Aged; Mood Disorders; ROC Curve; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Topics: Administration, Oral; Adolescent; Adult; Aged; Antidepressive Agents; Chromatography, High Pressure Liquid; Depressive Disorder; Dose-Response Relationship, Drug; Female; Fluvoxamine; Humans; Male; Metabolic Clearance Rate; Middle Aged; Sex Factors; Time Factors

There is still uncertainty regarding the best treatment optionfor depressed inpatients and the best strategy to follow if patient response is insufficient.. To compare the efficacy of imipramine and fluvoxamine in depressed inpatients who subsequently received lithium supplement in case of poor response.. After a drug-free period and four days of placebo use, patients were randomised either to imipramine or to fluvoxamine (phase 1); the antidepressant dosage was fixed according to a predetermined plasma level. The efficacy of the antidepressant was evaluated four weeks after the predetermined plasma level had been attained. If patient response was inadequate, the antidepressant was augmented with lithium (phase 2). Patient response to the lithium addition was evaluated three weeks after an adequate lithium level had been attained.. The study involved 138 inpatients. At the end of phase 1, imipramine was found to be superior tofluvoxamine according to the Clinical Global Impression of Improvement. Remission was achieved by 6 (23%) patients on imipramine and by 10 (15%) patients on fluvoxamine; this difference was not statistically significant. At the end of phase 2, 41 (9%) patients on imipramine and 27 (40%) patients on fluvoxamine achieved remission, this significant difference demonstrating the superiority of the imipramine strategy.. Imipramine with subsequent lithium addition is superior to a similar strategy with fluvoxamine.

Topics: Adult; Aged; Antidepressive Agents; Antidepressive Agents, Tricyclic; Depressive Disorder; Double-Blind Method; Drug Synergism; Female; Fluvoxamine; Humans; Imipramine; Lithium; Male; Middle Aged; Treatment Outcome

The present study aimed to compare the effects of two currently used selective serotonin reuptake inhibitors (SSRIs) in Japan taking the individual background in 5-HTT gene-linked polymorphic region (5HTTLPR) genotype into account. Clinical responses to paroxetine and fluvoxamine were evaluated by total and cluster depressive symptoms for 81 Japanese patients who were diagnosed with major depression. Patients with the l allele had a greater percentage reduction on the total score (P=0.059) and somatic anxiety items (P=0.026) of the 21-item Hamilton Depression Rating Scale (HAM-D) score compared to s/s genotype carriers. Paroxetine was significantly more effective than fluvoxamine in the s/s carriers, as evaluated on the percentage reduction in total score (P=0.012) and core (P=0.049) HAM-D after 4 weeks of medication, but not in the l/s carriers. These findings suggest that the genetic test may be useful in investigating the efficacy of the two SSRIs, and that normalization by the 5HTTLPR genotypes may lead to improvement of the precision of comparative analysis.

Topics: Adult; Antidepressive Agents, Second-Generation; Chromatography, High Pressure Liquid; Depressive Disorder; Female; Fluvoxamine; Genotype; Heterozygote; Humans; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Paroxetine; Patient Dropouts; Polymorphism, Genetic; Promoter Regions, Genetic; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins

Longitudinal studies with very long follow-up periods of patients with obsessive-compulsive disorder (OCD) who have received adequate treatment are rare. In the current study, 30 of 37 inpatients (81%) with severe OCD were followed up 6-8 years after treatment with cognitive-behavioral therapy (CBT) in combination with either fluvoxamine or placebo in a randomized design. The significant improvements (with large effectsizes) in obsessive-compulsive symptoms from pre- to post-treatment (41% reduction on the Y-BOCS) remained stable at follow-up (45 %). Responder rates, defined as > or = 35% reduction on the Y-BOCS, were 67% and 60%, respectively. Depressive symptoms decreased significantly not only from pre- to post-treatment but also during follow-up. Re-hospitalization, which occurred in 11 patients (37 %), was associated with more severe depressive symptoms at pre-treatment and living without a partner. Full symptom remission at follow-up, defined as both Y-BOCS total score < or = 7 and no longer meeting diagnostic criteria for OCD, was achieved by 8 patients (27 %). Patients without full remission at follow-up had a significantly longer history of OCD, assessed at pretreatment, compared to remitted patients. The shortterm treatment outcome had no predictive value for the long-term course. Throughout the naturalistic follow-up, nearly all patients (29 patients) received additional psychotherapy and/or medication. This might indicate that such chronic OCD patients usually need additional therapeutic support after effective inpatient treatment to maintain their improvements over long periods.

Topics: Adult; Age of Onset; Antidepressive Agents, Second-Generation; Cognitive Behavioral Therapy; Combined Modality Therapy; Depressive Disorder; Double-Blind Method; Employment; Female; Fluvoxamine; Follow-Up Studies; Hospitalization; Humans; Male; Marriage; Obsessive-Compulsive Disorder; Socioeconomic Factors; Treatment Outcome

With the example of treatment of menopause-related vegetative and emotional disturbances, the author verifies the effectiveness of the use of Ignatia amara containing complex homeopathic remedies (IACCHR) as an alternative to placebo. Substantial improvement in psychological and psychosomatic symptoms was observed. Climacteric complaints diminished or disappeared completely in the majority of women (95.7% by patient evaluation and 96.2% by physician evaluation). Compared to standard pharmaceuticals, IACCHR treatment was tolerated better and lower risk of side effects was observed. The results obtained in this work indicate the significant therapeutic potential of this group of treatments, which is in line with the therapeutic effect of the placebo. Nevertheless, the showing of specific effects in pharmacological tests disqualifies the investigated treatments from use in a clinical trial in place of a placebo.

Topics: Adult; Clinical Trials as Topic; Depressive Disorder; Drug Evaluation; Female; Fluvoxamine; Homeopathy; Hormone Replacement Therapy; Humans; Menopause; Middle Aged; Placebo Effect; Placebos; Plant Extracts; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

We investigated the effects of a 5-hydroxytryptamine (5-HT) 1A receptor gene polymorphism on the clinical response to fluvoxamine (FLV) in 65 depressed outpatients who gave written consent to participate in the study. Patients visited every 2 weeks after the first examination until the week 12 end point and were evaluated by the 17-item Hamilton Rating Scale for Depression (HAM-D-17) at each visit. FLV dose was changed in response to their clinical symptoms. The Gly272Asp polymorphism of the 5-HT1A receptor gene was identified by a PCR method. The subjects with the Asp allele had a significantly higher % reduction in the HAM-D-17 score than those with the Gly/Gly genotype at week 2 (P=0.009), week 6 (P=0.036), and week 12 (P=0.031). There was a significant difference in the genotype distribution between the responders and nonresponders. These results suggest that the Gly272Asp polymorphism of the 5-HT1A receptor gene may predict the response to FLV.

Topics: Adult; Antidepressive Agents, Second-Generation; Aspartic Acid; Depressive Disorder; Female; Fluvoxamine; Genotype; Glycine; Humans; Male; Receptor, Serotonin, 5-HT1A; Treatment Outcome

To evaluate the efficacy of the selective serotonin reuptake inhibitors (SSRIs) fluvoxamine and paroxetine in treating depression in the menopausal transition and to compare their efficacy, safety, side-effect profiles and drug compliance. One hundred and five perimenopausal patients (51.3 +/- 2.5 yr of age) were randomly assigned to receive a dosage of 50 mg/day of fluvoxamine (n=53) or 20 mg/day of paroxetine (n=52). The visual analog scale (VAS), Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) scores were evaluated before and after 3 months of therapy in the two groups of women. Significant reduction in HAM-D and HAM-A scores was observed in both groups of women, without significant difference between the two groups. VAS score in the fluvoxamine group (-62.6 +/- 5.2%) was significantly lower than that in the paroxetine group (-51.1 +/- 4.3%) (P < 0.0001). Although fluvoxamine compares favourably with paroxetine in rate of reduction of VAS score, this study suggests that both SSRIs are effective for and tolerated in depressed perimenopausal outpatients.

Topics: Antidepressive Agents, Second-Generation; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Menopause; Middle Aged; Paroxetine; Selective Serotonin Reuptake Inhibitors

The aim of the study is to test whether fluvoxamine affects the function of the hypothalamic pituitary adrenal (HPA) axis in female borderline (borderline personality disorder, BPD) patients with and without a history of sustained childhood abuse. Special attention is given to the presence of comorbid major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The HPA axis of 30 female BPD patients with (n = 17) and without (n = 13) a history of sustained childhood abuse was challenged with a combined dexamethasone and corticotropin releasing hormone test (DEX/CRH test) before and after 6 (n = 14) and 12 (n = 16) weeks of fluvoxamine treatment (150 mg/day). Both 6- and 12-week fluvoxamine treatments were associated with a significant and robust reduction of the adrenocorticotrophic hormone (ACTH) and cortisol response to the DEX/CRH test. The magnitude of the reduction was dependent on the presence of sustained childhood abuse, but not on the presence of comorbid MDD or PTSD: patients with a history of sustained childhood abuse showed the strongest reduction in ACTH and cortisol. In conclusion, Fluvoxamine treatment reduces the hyperresponsiveness of the HPA axis in BPD patients with a history of sustained childhood abuse. This effect is likely to be obtained in the first 6 weeks of treatment.

Topics: Adult; Antidepressive Agents, Second-Generation; Area Under Curve; Borderline Personality Disorder; Child; Child Abuse; Corticotropin-Releasing Hormone; Depressive Disorder; Dexamethasone; Female; Fluvoxamine; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Psychiatric Status Rating Scales; Stress Disorders, Post-Traumatic

Although selective serotonin reuptake inhibitors (SSRIs) are better tolerated than tricyclic antidepressants, their efficacy in severe depression remains to be further elucidated.. A double-blind, multicentre study was conducted in 86 severely depressed inpatients (>or= 25 on the 17-item Hamilton depression rating scale [HAMD] total score) to compare the efficacy and safety of fluvoxamine with that of clomipramine. Following placebo run-in, 86 patients were randomised to receive fluvoxamine or clomipramine (100-250 mg/day) for 8 weeks.. Fluvoxamine and clomipramine both resulted in marked improvements; there were no statistically significant differences between them on the 17-item HAMD total score, the clinical global impression severity of illness or global improvement items or the Montgomery-Asberg depression rating scale, at any visit. At the end of the study, 71% in the fluvoxamine group and 69% in the clomipramine group were responders (>or= 50% decrease in 17-item HAMD total score). However, fluvoxamine was better tolerated than clomipramine. Clomipramine was associated with a higher incidence of overall and treatment-related adverse events. In addition, the percentage of patients discontinued prematurely due to adverse events was more than twice as high with clomipramine than with fluvoxamine (24% vs 11%).. Fluvoxamine and clomipramine are equally effective in severe depression, but fluvoxamine has a better safety and tolerability profile.

Topics: Adult; Antidepressive Agents; Clomipramine; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Prospective Studies; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

The objective of this pilot study was to examine the relation between fluvoxamine (FVX) plasma concentrations, therapeutic response and side effects during a four-week treatment period. Twenty-two patients who met the DSM-IV criteria for major depression received 100 mg FVX during the first 2 days of treatment and then 150 or 200 mg/day. No clear relationship between plasma concentrations and side effects was detectable. A relationship between plasma concentrations and clinical efficacy was detectable after 21 days but not after 28 days of treatment. These preliminary results indicate that therapeutic drug monitoring might be useful for patients treated with FVX.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Depressive Disorder; Dose-Response Relationship, Drug; Female; Fluvoxamine; Humans; Linear Models; Male; Middle Aged; Pilot Projects

Atypical antipsychotics such as risperidone or olanzapine have been reported to be effective when added to a selective serotonin reuptake inhibitor (SSRI) in cases of depression in which treatment with an SSRI alone is not effective. It is possible that the combination of an SSRI and an atypical antipsychotic may be efficacious as an initial treatment for major depression.. Thirty-six subjects who fulfilled DSM-IV diagnostic criteria for major depressive disorder were given fluvoxamin, 50 or 75 mg/day, with risperidone, 0.5 or 1 mg/day, at the start of treatment. The dose of fluvoxamine was increased to 100 or 150 mg/day on the fourth day of the treatment and maintained thereafter. Hamilton Rating Scale for Depression (HAM-D) scores were obtained at base-line and every week for 6 weeks. Remission and response were defined, respectively, as > or = 75% and 50%-74% reduction from baseline in HAM-D score.. Of 30 subjects who completed the 6-week study, 23 (76%) achieved remission, 5 (17%) achieved response, and 2 (7%) were nonresponsive. Of the 6 patients who did not complete the study, 3 showed remission, 1 showed response, and 2 showed minimal or no response by the time of dropout. The reported adverse effects were mild, and none of the 36 subjects enrolled in the study manifested or reported extrapyramidal symptoms, nausea, or vomiting.. The results suggest that the combination of risperidone and fluvoxamine from the beginning of antidepressant therapy enhances the therapeutic response rate in depression.

Topics: Adolescent; Adult; Age Factors; Aged; Ambulatory Care; Antipsychotic Agents; Depressive Disorder; Drug Administration Schedule; Female; Fluvoxamine; Humans; Male; Middle Aged; Pilot Projects; Psychiatric Status Rating Scales; Risperidone; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

The aim of the present study was to test a possible effect of the monoamine oxidase A (MAOA) and serotonin receptor 2A (5-HT-2A) gene variants on the antidepressant activity of fluvoxamine and paroxetine in a sample of major (n = 248) and bipolar (n = 195) depressives, with or without psychotic features. A total of 443 in-patients were treated with 300 mg fluvoxamine (n = 307) or 20-40 mg paroxetine (n = 136) for 6 wk. The severity of depressive symptoms was assessed weekly with the Hamilton Rating Scale for Depression (HAMD). Allele variants were determined in each subject using a PCR-based technique. We observed a marginal association between 5-HT-2A variants and antidepressant response while MAOA genotypes were not associated. Possible stratification factors, such as sex, diagnosis, presence of psychotic features, HAMD scores at baseline, pindolol augmentation and SSRIs plasma levels did not significantly influence the observed results. The investigated MAOA and 5-HT-2A gene variants, therefore, do not seem to play a major role in SSRI antidepressant activity.

Topics: Adrenergic beta-Antagonists; Antidepressive Agents, Second-Generation; Antimanic Agents; Depressive Disorder; Depressive Disorder, Major; Double-Blind Method; Drug Synergism; Female; Fluvoxamine; Genotype; Humans; Lithium; Male; Middle Aged; Monoamine Oxidase; Paroxetine; Pindolol; Polymorphism, Genetic; Psychiatric Status Rating Scales; Receptor, Serotonin, 5-HT2A; Selective Serotonin Reuptake Inhibitors; Sex Characteristics

The purpose of this study was to investigate differences in outcome following treatment with two different antidepressants in depressed patients according to their pretreatment hormonal response to clonidine. In all, 62 drug-free DSM-IV recurrent major depressed patients and 20 normal controls were studied. Patients were subsequently treated for 4 weeks with fluoxetine (n=28), or amitriptyline (n=34), and were then classified as responders or nonresponders according to their final Hamilton depression scale score. Compared to controls, depressed patients showed lower GH response to CLO (DeltaGH) (P<0.0002). One control (5%) and 35 depressed patients (56%) had blunted DeltaGH values. The efficacy of the two antidepressants was not significantly different: 15 patients responded to AMI (44%), seven patients responded to FLUOX (25%) (P>0.15). However, in the subgroup of patients with blunted DeltaGH levels, the rate of responders was higher for AMI (11/21) compared to FLUOX (1/14) treated patients (P<0.01). These results suggest that in depressed patients a blunted GH response to CLO could predict antidepressant response.

Topics: Adrenergic alpha-Agonists; Adult; Amitriptyline; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Clonidine; Depressive Disorder; Female; Fluvoxamine; Human Growth Hormone; Humans; Male; Middle Aged; Norepinephrine; Psychiatric Status Rating Scales; Radioimmunoassay

The aim of the present study was to test a possible effect of the A218C tryptophan hydroxylase (TPH) gene variant on the antidepressant activity of fluvoxamine in a sample of major and bipolar depressives, with or without psychotic features. Two hundred and seventeen inpatients were treated with fluvoxamine 300 mg and either placebo or pindolol in a double blind design for 6 weeks. The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression. TPH allelic variants were determined in each subject by using a PCR-based technique. No significant finding was observed in the overall sample as well as in the pindolol group, while TPH*A/A was associated with a slower response to fluvoxamine treatment in subjects not taking pindolol (P = 0.001). This effect was independent from the previously reported influence of 5-HTTLPR polymorphism. If confirmed, these results may shed further light on the genetically determined component of the response to pharmacological treatments, thus helping the clinician to individualize each patient's therapy according to their genetic pattern.

Topics: Adult; Age of Onset; Alleles; Antidepressive Agents, Second-Generation; Bipolar Disorder; Carrier Proteins; Delusions; Depressive Disorder; Drug Synergism; Female; Fluvoxamine; Genetic Variation; Humans; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Pindolol; Polymerase Chain Reaction; Predictive Value of Tests; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins; Tryptophan Hydroxylase

10 patients with anxious and 10 patients with apathic-adynamic depressions were treated with fevarin. The efficiency of the drug and its influence on the psychopathologic structure were evaluated according to some scales. It was established that therapeutic action of fevarin manifests from the 1st week of therapy in patients with anxious depressions due to its anxiolytic properties. In apathic-adynamic depressions the reduction of the symptoms was revealed by the 3-4 week of the therapy. The antidepressive effect of fevarin was retarded and didn't depend on the structure of the depression. Higher efficiency of the drug in patients with anxious depressions was explained by combination of thymoanaleptic and anxiolytic effects. The results of the study demonstrate a perspective of fevarin in therapy of anxious and apathic-adynamic depressions.

Topics: Anxiety Disorders; Depressive Disorder; Fluvoxamine; Humans; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index

30 patients suffered from psychogeneous depressions with anxiety have been treated with the fluvoxamine (100-300 mg/day) by 8 weeks. The disorder have been developed after the severe psychogenic trauma--the death of one of the close relatives. Assessment of the fluvoxamine efficacy and safety have been carried out by means of both the data of the psychopathological investigation and of some rating scales: Clinical Global Impression Scale--CGI, the Hamilton Depression Scale--HAM-D, the Scale of Side Effects, etc.). The pronounced clinical improvement have been achieved in 63.3% of cases beginning from the 2nd week of treatment. HAM-D scores decreased from 27 to 9 (p < 0.01). The reduction of the anxious and depressive symptoms occurred synchronously but reduction of somatic anxiety preceded the psychotic one. The side effects (sleepiness, nausea, etc.) have been noted only in 7 cases (23.3%) during the 1st week of treatment, and then disappeared.

Topics: Adult; Antidepressive Agents, Second-Generation; Depressive Disorder; Female; Fluvoxamine; Humans; Male

To determine whether problem solving treatment combined with antidepressant medication is more effective than either treatment alone in the management of major depression in primary care. To assess the effectiveness of problem solving treatment when given by practice nurses compared with general practitioners when both have been trained in the technique.. Randomised controlled trial with four treatment groups.. Primary care in Oxfordshire.. Patients aged 18-65 years with major depression on the research diagnostic criteria-a score of 13 or more on the 17 item Hamilton rating scale for depression and a minimum duration of illness of four weeks.. Problem solving treatment by research general practitioner or research practice nurse or antidepressant medication or a combination of problem solving treatment and antidepressant medication.. Hamilton rating scale for depression, Beck depression inventory, clinical interview schedule (revised), and the modified social adjustment schedule assessed at 6, 12, and 52 weeks.. Patients in all groups showed a clear improvement over 12 weeks. The combination of problem solving treatment and antidepressant medication was no more effective than either treatment alone. There was no difference in outcome irrespective of who delivered the problem solving treatment.. Problem solving treatment is an effective treatment for depressive disorders in primary care. The treatment can be delivered by suitably trained practice nurses or general practitioners. The combination of this treatment with antidepressant medication is no more effective than either treatment alone.

Topics: Adolescent; Adult; Aged; Algorithms; Antidepressive Agents; Antidepressive Agents, Second-Generation; Combined Modality Therapy; Depressive Disorder; Fluvoxamine; Humans; Middle Aged; Paroxetine; Problem Solving; Psychotherapy; Treatment Outcome

The evolution of kinetic parameters (Vmax, maximal velocity, and Km, Michaelis constant) of red blood cell (RBC) triiodothyronine (L-T3) initial uptake was followed in 19 inpatients suffering from unipolar depression after 1 week (D7) and 4 weeks (D28) of a chronic administration of fluvoxamine, in relation with the clinical efficacy of the drug. In a drug-free state (DO), Vmax (in pmol/min/10(8) cells) and Km (in nM) were significantly increased in depressed patients (Vmax +/- S.D.= 1.02 +/- 0.29, p< 0.01 and Km +/- S.D.= 68.8 +/-15.4, p< 0.05; n=19) compared to healthy volunteers matched for age and sex (Vmax +/- S.D.= 0.82 +/- 0.15 and Km S.D.= 58.8 +/- 9.0; n= 19). When patients were dichotomized on the basis of their treatment response, responders had kinetic parameters significantly increased (Vmax +/-S.D.= 1.03 +/- 0.26, p< 0.01 and Km +/- S.D.= 71.7 +/- 18.7, p< 0.05, n= 10) compared to controls, whereas non-responders had not (Vmax +/- S.D.= 1.00 +/- 0.33, NS and Km +/- S.D.= 65.7 +/- 10.9, NS, n= 9). At D7, Vmax differed from the one of controls only in the responders (Vmax +/- S.D.= 1.03 +/-0.26, p< 0.01). In addition, the percentage of variation of the individual Vmax values during the first week of treatment was significantly lower in responders than in non-responders (deltaVmax(D7-D0) +/- S.D. in % = 10.7 +/- 6.0 and 22.0 +/- 11. 1, p< 0.05, respectively). At D28, kinetics of L-T3 uptake normalized only in the responders (Vmax +/- S.D.= 0.91 +/- 0.13, NS; Km+/-S.D.= 65.7 +/- 7.4, NS). The results indicate that both RBC L-T3 uptake at the pretreatment level and its change during the first week of fluvoxamine treatment were related to the further clinical response to the antidepressant. RBC L-T3 uptake seems to be a biological correlate of the depressive symptomatology since the disturbances disappear only with the clinical remission.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Depressive Disorder; Erythrocytes; Female; Fluvoxamine; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Thyroid Function Tests; Thyrotropin; Triiodothyronine

Previous studies have reported the efficacy of selective serotonin reuptake inhibitors as monotherapy in the treatment of delusional depression. The clinical efficacy of venlafaxine, a serotonin-norepinephrine reuptake blocker, has been demonstrated in the treatment of patients with moderate-to-severe depression, but, to date, no evidence is available about its use in depressed patients with psychotic features.. Under double-blind conditions, 28 hospitalized patients who met DSM-IV criteria for major depression, severe with psychotic features, were randomly assigned to receive fluvoxamine or venlafaxine, 300 mg/day, for 6 weeks. Severity was evaluated using the Hamilton Rating Scale for Depression (HAM-D) and the Dimensions of Delusional Experience Rating Scale (DDERS) administered at baseline and every week thereafter. Side effects were also recorded. Clinical response was defined as a reduction of the scores in the 21-item HAM-D to 8 or below and in the DDERS to 0.. At study completion, the response rates were 78.6% (N = 11) and 58.3% (N = 7) for fluvoxamine and venlafaxine, respectively. No significant difference was found between drugs (Fisher exact test, p = .40). Analysis of covariance on HAM-D scores did not reveal a significantly different decrease of depressive symptomatology between the 2 treatment groups (p = .14). Treatment response appeared to be unrelated to the demographic and clinical characteristics recorded. The overall safety profile of both fluvoxamine and venlafaxine was favorable.. The results of this pilot double-blind trial show that fluvoxamine is useful in the treatment of delusional depression and suggest that venlafaxine may also be an effective compound in the treatment of this disorder. The latter finding, although promising, warrants further replication in a larger sample of patients.

Topics: Adult; Affective Disorders, Psychotic; Cyclohexanols; Delusions; Depressive Disorder; Double-Blind Method; Drug Administration Schedule; Female; Fluvoxamine; Humans; Male; Middle Aged; Pilot Projects; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Venlafaxine Hydrochloride

We prolonged from 24 to 48 months a follow-up study of unipolar subjects with high recurrence rate treated with fluvoxamine (N=25) and sertraline (N=22). During the two-year additional period a significant risk of recurrences was observed during the third year of follow-up, without differences in the two long-term therapy groups. During the fourth year no patients showed new episodes of illness.

Topics: Adult; Antidepressive Agents; Antidepressive Agents, Second-Generation; Depressive Disorder; Female; Fluvoxamine; Follow-Up Studies; Humans; Male; Middle Aged; Recurrence; Sertraline; Treatment Outcome

To compare the emergent sexual effects of moclobemide and selective serotonin reuptake inhibitors (SSRIs) during acute and maintenance therapy in routine practice.. 268 patients were evaluated for sexual function at baseline, 6 weeks, 3 and 6 months of treatment using physician ratings and self-rating questionnaires. Patients received moclobemide, an reversible monoamine oxidase A inhibitor (RIMA), or a SSRI (fluoxetine, fluvoxamine, paroxetine, sertraline).. Baseline values were similar in all groups. Incidences of impairments of sexual functioning with treatment, whether clinically relevant or not, were 24.3% with moclobemide and 61.5% with SSRIs (physician ratings), with no significant tolerance to these effects. There was a suggestion of differences between the SSRIs in their specific dysfunctions they cause. SSRIs (21.6% of patients) had about ten times the moclobemide rate (1.9%) of sexual dysfunction reported as adverse events. Antidepressant efficacy was comparable between treatments.. In patients for whom sexual function is important or sexual dysfunction is present, moclobemide should be considered a first line antidepressant.

Topics: Adult; Antidepressive Agents; Depressive Disorder; Drug Therapy, Combination; Female; Fluoxetine; Fluvoxamine; Humans; Libido; Male; Middle Aged; Moclobemide; Monoamine Oxidase Inhibitors; Paroxetine; Prospective Studies; Selective Serotonin Reuptake Inhibitors; Sertraline; Sexual Behavior; Surveys and Questionnaires; Time Factors

Fifty-seven highly recurrent unipolar patients, excluded from previous long-term studies with selective serotonin reuptake inhibitors (SSRIs) after they experienced a new recurrence, were acutely treated with the full dosage of the SSRIs they were on. Fifty-one of them (89.5%) had a sustained response and entered into the 4-month continuation therapy. During this phase, no relapse was observed. At the end of it, all patients gave their written informed consent to be enrolled in a 24-month long-term therapy, maintaining the same treatment dosage of fluvoxamine 300 mg/day, sertraline 150 mg/day, or paroxetine 40 mg/day. At the end of the study, 28 out of the 51 outpatients (54.9%) showed a further recurrence. Nevertheless, second recurrences observed during this second maintenance therapy were less severe than first recurrences, decreasing from 25.1+/-3.4 to 21.6+/-3.3 (P<0.0001), respectively. Considering the clinical characteristics of patients, we found that a high number of prior depressive episodes and an early age at onset of illness may predict a bad outcome. Moreover, patients with a longer duration of euthymia during a first maintenance period are less likely to have a new episode of depression.

Topics: Adult; Depressive Disorder; Dose-Response Relationship, Drug; Female; Fluvoxamine; Humans; Male; Middle Aged; Paroxetine; Proportional Hazards Models; Risk Factors; Secondary Prevention; Selective Serotonin Reuptake Inhibitors; Sertraline; Severity of Illness Index; Treatment Outcome

30 patients of 23-73 years old with endogenic and reactive depressions were treated with fevarin. The clinical state of the patients was estimated by means of Hamilton Depression Rating Scale (Ham-D). Fevarin was administrated in daily dose of 100-300 mg; the course of the treatment was equal to 4-8 weeks. The anxiolytic and antidepressive effects of fevarin were developed from the 5-7 days of the therapy: an anxiety disappeared completely by the end of the 3-d week. The most pronounced antidepressive effect was found for the classic depression with melancholy. A mild simulative effect and a normalization of a sleep were also observed. An improvement of the mental state was found in the all the patients by the end of the treatment: in 60% it was significant (a complete remission); in 40%--a considerable improvement was observed with the reduction of all clinical components of the depressive state. Fluvoxamine was found to be the high effective preparation for both endogenic and reactive depressions.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Depressive Disorder; Drug Administration Schedule; Female; Fluvoxamine; Humans; Male; Middle Aged; Severity of Illness Index; Treatment Outcome

Central serotonin dysfunction is thought to be involved in the etiology of major depression. Serotonergic challenge studies before and after treatment of depressed patients have yielded conflicting results; however, these studies have not focused on the effect of antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs) on serotonergic challenge studies.. The authors studied 19 outpatients with major depressive disorder using prolactin response to d-fenfluramine as a measure of central serotonergic functioning. Testing of patients was conducted just before and right after 8 weeks of treatment with either fluoxetine (n = 10) or fluvoxamine (n = 9) as part of a randomized, double-blind treatment trial. Blood samples for prolactin were collected prior to administration of d-fenfluramine (0.5 mg/kg) and then over the next 5 hours.. Unlike previous studies in which antidepressant treatment produced an enhanced prolactin response to fenfluramine, in this study there was no increase in prolactin response to d-fenfluramine following SSRI treatment. In fact, prolactin response to d-fenfluramine was significantly diminished after treatment with fluvoxamine but not fluoxetine.. The implications of these findings are discussed with regard to possible mechanisms of action of SSRI treatment.

Topics: Adult; Analysis of Variance; Depressive Disorder; Double-Blind Method; Female; Fenfluramine; Fluoxetine; Fluvoxamine; Humans; Male; Prolactin; Prospective Studies; Selective Serotonin Reuptake Inhibitors; Time Factors

Pindolol has been reported to hasten the antidepressant action of selective serotonin reuptake inhibitors in open-label and placebo-controlled trials. Pilot studies also suggested that pindolol could augment the antidepressant response in unresponsive patients. We investigated whether the addition of pindolol can induce a rapid response in treatment-resistant patients.. After a single-blind lead-in placebo phase of 5 days to exclude placebo responders, 80 outpatients with major depression who did not respond to a minimum of 6 weeks of treatment with clomipramine hydrochloride, 150 mg/d; fluoxetine hydrochloride, 40 mg/d; fluvoxamine maleate, 200 mg/d; or paroxetine hydrochloride, 40 mg/d, were randomly assigned to additionally receive placebo (3 times daily) or pindolol (2.5 mg 3 times daily) for 10 days. The median number of ineffective treatments in the current episode was 2 (range, 1-4). Hamilton Rating Scale for Depression and Montgomery-Asberg Scale for Depression scores were used as primary measures of efficacy.. At end point, the Hamilton and Montgomery-Asberg scores and change from baseline in Hamilton score were not significantly different in patients taking placebo or pindolol. The response rate was equal in both groups (12.5%). No differences in the clinical outcome were found when the various pretreatment subgroups were considered. At end point, the plasma concentration of pindolol was 9.9+/-5.1 ng/mL (mean +/- SD; n = 40).. Although pindolol can accelerate the antidepressant action of selective serotonin reuptake inhibitors in previously untreated patients, it does not elicit a rapid clinical response in treatment-resistant patients within a 10-day period.

Topics: Adult; Ambulatory Care; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Evaluation; Drug Synergism; Drug Therapy, Combination; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Paroxetine; Pindolol; Placebos; Selective Serotonin Reuptake Inhibitors; Single-Blind Method

Fluvoxamine (FLUVOX) is an inhibitor of the cytochrome P450 isoenzyme 1 A2 and thereby inhibits clozapine (CLOZ) metabolism. We performed an open clinical study to gather experience in necessary dosages, plasma levels, side effects and clinical efficiency of the coadministration of the two drugs. Eighteen psychotic patients were studied. 50 mg FLUVOX were given throughout the study period, while the CLOZ dosage was increased individually (week 5: 96.9+/-37.2 mg). After 5 weeks the plasma concentrations were as follows: CLOZ 252+/-174 ng/ml, N-desmethylclozapine (DM-CLOZ) 143+/-74 ng/ml and clozapine N-oxide (CLOZ N-OX) 30+/-14 ng/ml. There were no differences in side effects, especially sedation, after 5 weeks compared to the pretreatment condition. Moreover, we found a significant improvement in measures of cognitive speed which might be regarded as a measure of vigilance. The BPRS scores dropped continuously until week 5 (pretreatment: 53.3+/-13.4; week 5: 33.2+/-12.9) and 5 patients were considered treatment responders (BPRS reduction > 50%). Ten patients continued the combination treatment after the study period and 9 of these patients were in clinical remission when discharged. Given strict therapeutic drug monitoring, coadministration of FLUVOX and CLOZ seems to be a safe and efficient treatment strategy with a low occurrence of the side effects associated with CLOZ treatment. This might be due to additive effects of the two drugs and/or metabolic interaction.

Topics: Adult; Anti-Anxiety Agents; Antipsychotic Agents; Clozapine; Depressive Disorder; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Male; Psychotic Disorders; Schizophrenia; Schizophrenia, Paranoid

Major depression with comorbid anxiety disorder is associated with poor antidepressant outcome compared with major depression without comorbid anxiety disorder. The purpose of our study was to assess changes in depressive symptoms and anxiety levels in outpatients with major depression with comorbid anxiety disorder following 12 weeks of open treatment with fluvoxamine.. We enrolled 30 outpatients (mean +/- SD age = 39.4 +/- 11.3 years; 16 women and 14 men) with DSM-IV major depressive disorder accompanied by one or more current comorbid DSM-IV anxiety disorders in our study. Patients were treated openly with fluvoxamine initiated at 50 mg/day, with an upward titration to a maximum of 200 mg/day (mean +/- SD dose = 143 +/- 45 mg/day). Efficacy assessments included the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and Clinical Global Impressions-Severity of Illness (CGI-S) and Improvement (CGI-I) scales for both depression and anxiety. Intent-to-treat analysis was used to assess outcome.. The mean +/- SD number of comorbid anxiety disorders per patient was 2.1 +/- 1.1. Following fluvoxamine treatment, the mean +/- SD HAM-D-17 score dropped from 20.2 +/- 3.3 to 1 1.0 +/- 7.0 (p < .0001). The mean +/- SD depression CGI-S score dropped from 4.0 +/- 0.6 to 2.4 +/- 1.1 (p < .0001), and the mean +/- SD anxiety CGI-S score decreased from 4.1 +/- 0.8 to 2.5 +/- 1.2 (p < .0001). Eighteen (60%) of the 30 patients had CGI-I scores < or = 2 for both anxiety and depression at endpoint, with 53% showing a > or = 50% reduction in HAM-D-17 scores at endpoint.. Although preliminary, our findings suggest that fluvoxamine is effective in treating outpatients with major depression with comorbid anxiety disorder, having a significant effect on both depression and anxiety symptoms. Further double-blind, placebo-controlled trials are needed, in a larger sample, to confirm our findings.

Topics: Adolescent; Adult; Aged; Ambulatory Care; Anxiety Disorders; Comorbidity; Depressive Disorder; Drug Administration Schedule; Female; Fluvoxamine; Humans; Male; Middle Aged; Patient Dropouts; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Treatment Outcome

This study quantifies functional impairment and depressive symptomatology in patients with minor depressive disorder (MinD) and subsyndromal depressive symptomatology (SSD) before and after 8 weeks of treatment with fluvoxamine. Study patients were compared and contrasted with archival data from a sample of the general population measured by the Medical Outcome Survey Short Form 36.. Fifteen patients with MinD and 15 patients with SSD were identified from primary care clinics, referrals and newspaper advertisements. Patients signed informed consent and were offered open label treatment with fluvoxamine 25-100 mg/day. Patients were seen biweekly and measures of functional impairment and depressive symptomatology were gathered systematically.. MinD and SSD were associated with dysfunction and disability when compared to archival normative data from the general population. Eight week treatment with fluvoxamine was associated with a substantial decrease in depressive symptomatology and a normalization of psychosocial functioning.. This is the first study to quantify functional impairment and the severity of depressive symptomatology in a clinical sample of patients with MinD and SSD, and to demonstrate that treatment with a selective serotonin reuptake inhibitor decreases depressive symptomatology and improves psychosocial functioning. Placebo-controlled double-blind confirmation of these preliminary observations seems warranted.

Topics: Antidepressive Agents, Second-Generation; Cost of Illness; Depression; Depressive Disorder; Female; Fluvoxamine; Follow-Up Studies; Humans; Male; Middle Aged; Pilot Projects; Quality of Life; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Social Adjustment; Treatment Outcome

Body dysmorphic disorder (BDD), a preoccupation with an imagined or slight defect in appearance, has been noted in case reports, retrospective studies, and clinical series to respond to serotonin reuptake inhibitors (SRIs). These data further suggest that the delusional variant of BDD (delusional disorder, somatic type) may also respond to SRIs. However, systematic pharmacologic treatment studies of BDD and its delusional variant are needed.. Thirty subjects with BDD or its delusional variant (DSM-IV) were prospectively treated in an open-label fashion with fluvoxamine for 16 weeks. Subjects were assessed at regular intervals with the Yale-Brown Obsessive Compulsive Scale Modified for BDD (BDD-YBOCS), the Clinical Global Impressions (CGI) scale, the Hamilton Rating Scale for Depression, the Brown Assessment of Beliefs Scale, and other measures.. BDD-YBOCS scores (mean +/- SD) decreased from 31.1 +/- 5.4 at baseline to 16.9 +/- 11.8 at termination (p < .001). Nineteen (63.3%) subjects were rated as responders on the BDD-YBOCS and the CGI (10 [33.3%] were much improved, and 9 [30.0%] were very much improved). Delusional subjects were as likely to respond to fluvoxamine as nondelusional subjects, and delusionality significantly improved. All 5 responders who were delusional at baseline were no longer delusional at study endpoint. The mean dose of fluvoxamine was 238.3 +/- 85.8 mg/day, and mean time to response was 6.1 +/- 3.7 weeks. Fluvoxamine was generally well tolerated.. These results suggest that fluvoxamine is a safe and effective treatment for BDD, including its delusional disorder variant. Controlled treatment trials are needed to confirm these findings.

Topics: Adult; Ambulatory Care; Comorbidity; Delusions; Depressive Disorder; Drug Administration Schedule; Female; Fluvoxamine; Humans; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Somatoform Disorders; Treatment Outcome

Previous findings showed that, in a subgroup of patients administered heterogeneous antidepressant treatments, perceived mood levels during a major depressive episode fluctuate with day to day changes which follow cyclical patterns (termed "minicycles"). We investigated the predictability of infradian mood fluctuations during acute depressive episodes in patients standardly medicated with fluvoxamine. We applied time series analysis, by means of autocorrelation techniques, to time lagged serial recordings of perceived mood levels of 20 inpatients (13 Major Depression Recurrent, and 7 Bipolar Depressive Disorders). 5/20 patients exhibited predictable cyclical patterns in their perceived symptomathology, 8/20 exhibited an uneven, sawtooth pattern of progressive amelioration, and 7/20 showed an erratic pattern of unpredictable day-to-day variations. We confirmed the existence and the predictability of cyclical mood patterns in a subgroup of patients. The absence of a linear improvement in perceived mood did not worsen the final response to antidepressant therapy.

Topics: Antidepressive Agents, Second-Generation; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Middle Aged; Periodicity; Time Factors

The syndrome of mixed anxiety and depression (MAD) has been described and is familiar to both general psychiatrists and nonpsychiatrists. It was included in the DSM-IV appendix as a syndrome proposed for further study. Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) approved for the treatment of obsessive-compulsive disorder, was studied for its effectiveness in treating anxiety and depression simultaneously during an 8-week, open-label trial of patients with MAD. Thirteen patients were included in the final, intent-to-treat, analysis. Fluvoxamine showed moderately strong effectiveness in improving anxiety and depression with a greater effect on the depressive component. Nausea, insomnia, delayed ejaculation, and nervousness were the most common side effects reported, with no serious adverse events occurring. Future double-blind placebo-controlled studies will give more conclusive results.

Topics: Adult; Antidepressive Agents, Second-Generation; Anxiety Disorders; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Middle Aged; Pilot Projects; Psychiatric Status Rating Scales

This double-blind placebo-controlled study specifically tested the efficacy of fluvoxamine, at a dose of 100 mg a day, in reducing the risk of new episodes of depression. Out of 436 patients treated openly with fluvoxamine 283 patients fulfilled stringent criteria to define responders at 6 weeks. A total of 204 patients maintained their remission throughout a continuation treatment period of 18 weeks and then entered the prophylactic study. They were randomly assigned to receive either fluvoxamine 100 mg a day or placebo for 1 year. There were significantly fewer recurrences of new episodes of depression in the fluvoxamine group compared with the placebo group (p < 0.001). The significant advantage for fluvoxamine was also seen in the Kaplan-Meier analysis of time to recurrence (p < 0.001). The clear-cut efficacy of 100 mg of fluvoxamine and the good tolerability and side-effect profile demonstrated in this study support the view that fluvoxamine is particularly suitable for maintenance or prophylactic treatment.

Topics: Adolescent; Adult; Aged; Antidepressive Agents, Second-Generation; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Recurrence; Risk Factors

This pilot study examined prospectively blood serum concentrations of fluvoxamine, side effects and therapeutic response after a fixed dosage of 100 mg fluvoxamine/day for 14 days. Twenty male and female patients who met the DSM-IV criteria of a major depression received 50 mg fluvoxamine b.i.d. for two weeks. On days 7 and 14 side effects and therapeutic response were registered and serum concentrations of fluvoxamine were determined. A Receiver Operating Characteristic (ROC) curve was constructed to determine a possible relationship between serum concentrations and clinical effects. The serum concentrations of fluvoxamine were highly variable, even when dosages were corrected for body weight, ranging between 23 to 227 microg/l. No relationship between serum concentrations and side effects was detectable. On the other hand, ROC analysis, conducted on day 14, revealed a significant upper concentration threshold of 85 microg/l (p < 0.01) with no responder above this threshold. The results of this pilot study should be regarded as a hint at the possible therapeutic benefits of lower fluvoxamine serum concentrations by means of lower fluvoxamine dosages. Furthermore, this indicates for the first time that therapeutic drug monitoring might be useful for patients under antidepressant therapy with fluvoxamine.

Topics: Adult; Aged; Aged, 80 and over; Antidepressive Agents, Second-Generation; Depressive Disorder; Drug Monitoring; Female; Fluvoxamine; Humans; Male; Middle Aged; Prospective Studies; ROC Curve

Depression with psychotic features has been shown to respond to selective serotonin reuptake inhibitors (SSRIs). The serotonin transporter (5-HTT) is a prime target for SSRIs. A functional polymorphism within the promoter region of the 5-HTT gene, leading to different transcriptional efficiency, was recently reported. We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antidepressant response to fluvoxamine and/or augmentation with pindolol (a serotonin autoreceptors antagonist) which has been suggested as an augmentation therapy for nonresponders. One hundred and two inpatients with major depression with psychotic features were randomly assigned to treatment with a fixed dose of fluvoxamine and either placebo or pindolol for 6 weeks. Depression severity was assessed once a week using the Hamilton Depression Rating Scale. Allelic variation in each subject was determined using a PCR-based method. Data were analyzed with a three-way repeated measures analysis of variance. Both homozygotes for the long variant (l/l) of the 5-HTT promoter and heterozygotes (l/s) showed a better response to fluvoxamine than homozygotes for the short variant (s/s). In the group treated with fluvoxamine plus pindolol all the genotypes acted like l/l treated with fluvoxamine alone. Fluvoxamine efficacy in delusional depression seems to be related to allelic variation within the promoter of the 5-HTT gene. Even though other factors may be implicated, genotyping at 5-HTT promoter may represent a promising tool to individualize the pharmacological treatment of depression.

Topics: Antidepressive Agents, Second-Generation; Carrier Proteins; Depressive Disorder; Drug Therapy, Combination; Female; Fluvoxamine; Genotype; Humans; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Pindolol; Polymorphism, Genetic; Predictive Value of Tests; Promoter Regions, Genetic; Serotonin Antagonists; Serotonin Plasma Membrane Transport Proteins

Selective serotonin reuptake inhibitors (SSRIs) are the 'new' drugs of first choice for the treatment of depression in the older patient. Systematic studies on the effects of SSRIs on cardiac function are scarce, despite the high prevalence of cardiac disorders in the older depressed patient. This is a study which systematically assessed cardiac function by echocardiography in middle-aged and elderly depressed patients treated with SSRI. In a double-blind randomized trial, 20 patients were assigned to receive fluvoxamine 100 mg/day [DOSAGE ERROR CORRECTED] or fluoxetine 20 mg/day [DOSAGE ERROR CORRECTED] for 6 weeks. Cardiac function was assessed by left ventricle ejection fraction, aortic flow integral and early or passive/late or active mitral inflow, and electrocardiography. Neither SSRI significantly affected cardiac function. Compared with patients without a history of myocardial infarction and/or hypertension, patients with such a history showed a significant improvement in left ventricular ejection fraction. Despite our small study sample, these data indicate that both fluoxetine and fluvoxamine do not affect cardiac function adversely.

Topics: Aged; Aged, 80 and over; Cardiovascular Diseases; Depressive Disorder; Double-Blind Method; Echocardiography; Electrocardiography; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Selective Serotonin Reuptake Inhibitors

We sought to determine whether fluvoxamine and fluoxetine, two different antidepressants with in vitro selectivity for the serotonin uptake transporter also demonstrated similar selectivity in vivo. To accomplish this, we measured cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) before and after 6 weeks of treatment with these two drugs. Twenty-four subjects who had major depression according to DSM-III-R criteria gave written, informed consent for the collection of CSF during a double-blind comparative treatment trial of fluvoxamine (50-150 mg/day) and fluoxetine (20-80 mg/day). The symptoms of subjects were assessed clinically on a weekly basis throughout the treatment trial. CSF samples were obtained after a 7- to 14-day washout period before treatment and again at the end of treatment. CSF samples were analyzed for 5-HIAA, HVA, and MHPG using high-pressure liquid chromatography coupled to electrochemical detection. Fluvoxamine- and fluoxetine-treated patients did not differ in clinical outcome or in the CSF concentrations of monoamine metabolite levels before or after treatment. Therefore, the CSF data were pooled. Drug treatment, overall, was associated with significant decreases in 5-HIAA and MHPG and a trend toward a reduction in HVA levels. Levels of 5-HIAA, MHPG, and HVA were reduced by 57%, 48%, and 17%, respectively. In addition, the magnitude of the decreases in 5-HIAA and MHPG appeared to be correlated (r = 0.83) across the subjects, although a Spearman rank correlation indicated that outlying values had an undue effect on this relationship. These results suggest that treatment with selective serotonin reuptake inhibitors, which are selective for serotonin uptake in vitro, does not show a similarly selective effect on serotonin in vivo during treatment of patients.

Topics: Adult; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluoxetine; Fluvoxamine; Follow-Up Studies; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Male; Methoxyhydroxyphenylglycol; Middle Aged; Selective Serotonin Reuptake Inhibitors

We evaluated and compared the efficacy and safety of sertraline and fluvoxamine in a randomized, double-blind, parallel-group study during a follow-up of 24 months.. Sixty-four patients with recurrent, unipolar depression (DSM-IV criteria) who had at least one depressive episode during the 18 months preceding the index episode were accepted into the trial. Patients were randomly assigned to one of the two long-term treatment groups and evaluated monthly by trained psychiatrists, blinded to treatment option, on the basis of the Hamilton Rating Scale for Depression.. All patients completed the 24-month follow-up period. Sertraline and fluvoxamine showed an equal efficacy in preventing new recurrences. In fact, there was no significant difference in survival rates between the two medication groups: 7 sertraline-treated patients (21.9%) and 6 fluvoxamine-treated patients (18.7%) had a single new recurrence (z = 0.14; p = .88). Moreover, recurrence observed during maintenance therapies was less severe and/or of shorter duration than index episodes.. Long-term treatment with sertraline or fluvoxamine has been shown to be effective for prevention of highly recurrent unipolar depression. The high tolerability of these compounds, together with their prophylactic effectiveness, has an important role in improving the quality of life of these patients.

Topics: 1-Naphthylamine; Depressive Disorder; Double-Blind Method; Drug Therapy, Combination; Fluvoxamine; Follow-Up Studies; Humans; Recurrence; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

We hypothesized that the probability of personality disorder ('PROB') predicted by the Temperament and Character Inventory ('TCI') would decline after successful pharmacotherapy of depression.. We administered a computerized version of the TCI to 15 patients with DSM-III-R major depression, before and after treatment with serotonergic antidepressants.. PROB declined from 58.9% +/- 18.0% to 42.4% +/- 22.8% (P < 0.003), due to a significant increase in the Self-Directedness scale. This change in PROB correlated with improvement in self-rated severity of depression (P < 0.02).. TCI prediction of personality disorder is susceptible to state effects of depression.

Topics: Adult; Antidepressive Agents, Second-Generation; Depressive Disorder; Ergolines; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Paroxetine; Personality Disorders; Personality Inventory; Serotonin Antagonists

Fluvoxamine and paroxetine, both serotonin selective reuptake inhibitors (SSRIs), were compared at two centers in a 7-week double-blind study in outpatients with major depression, diagnosed by DSM-III-R criteria.. Sixty patients were randomly assigned to receive dosage titrated upward to between 50-150 mg/day of fluvoxamine (N = 30) or 20-50 mg/day of paroxetine (N = 30). The mean +/- SD daily dose administered at the last assessment was 102 +/- 44 mg/day for fluvoxamine and 36 +/- 13 mg/day for paroxetine. Sixteen (53%) fluvoxamine-treated patients and 10 (33%) paroxetine-treated patients were titrated to the maximum permissible dosage of either drug. Sample size was calculated to provide at least 85% power at 5% level of significance to detect at least a 1.00-point difference in mean severity of adverse events, assuming a standard deviation of 1.0.. Fluvoxamine and paroxetine were similarly effective in ameliorating depression as demonstrated by mean total scores of 10.9 +/- 7.3 (p < .00) and 11.5 +/- 7.4 (p < .00), respectively, in the Hamilton Rating Scale for Depression (HAM-D). Adverse events were mostly mild to moderate in severity. The most common events were headache (N = 17, 57%), nausea (N = 14, 47%), sweating (N = 10, 33%), somnolence (N = 9, 30%), diarrhea (N = 9, 30%), dry mouth (N = 8, 27%), dizziness (N = 8, 27%), and, among males, impotence (N = 3, 21%) and ejaculatory abnormality (N = 3, 21%) in the paroxetine group, and headache (N = 12, 40%), somnolence (N = 12, 40%), nausea (N = 11, 37%), dry mouth (N = 11, 37%), insomnia (N = 9, 30%), asthenia (N = 7, 23%), and dyspepsia (N = 7, 23%) in the fluvoxamine group. The only statistically significant difference between treatment groups was for sweating (33% paroxetine vs. 10% fluvoxamine, p = .028).. Observed differences in some side effects, although not statistically significant, indicate that when a patient has difficulty tolerating one SSRI, the clinician may choose to change to a different agent within the same class.

Topics: Adolescent; Adult; Aged; Ambulatory Care; Depressive Disorder; Diarrhea; Double-Blind Method; Drug Administration Schedule; Female; Fluvoxamine; Headache; Humans; Male; Middle Aged; Nausea; Paroxetine; Psychiatric Status Rating Scales; Severity of Illness Index; Sleep; Sweating; Treatment Outcome; Xerostomia

Parallel groups of depressed (DSM III-R) outpatients received moclobemide (n = 22) and fluoxetine (n = 19), double blind, for 6 weeks. Respective starting doses were 150 mg twice a day and 20 mg q.a.m. These could be doubled after 3 weeks for greater efficacy. Chronic users of benzodiazepine anxiolytics continued taking them as comedication. Therapeutic and side effects were assessed using conventional rating scales. Actual driving performance was assessed during the week before therapy and at 1, 3 and 6 weeks thereafter using a standardized test that measures standard deviation of lateral position (SDLP). Similar remissions in depressive symptoms and side effects occurred in both groups. Patients drove with normal and reliable (r = 0.87) SDLPs before treatments. Most continued to do so but a few drove with progressively rising SDLPs and the overall trends were significant in both groups (p < 0.03). A post-hoc multiple regression analysis was applied for identifying factors that correlated with SDLP in separate tests after the beginning of therapy. At 3 and 6 weeks there were significant (p < 0.03) relationships involving the same factor; patients who drove with progressively higher SDLPs appeared to be those using benzodiazepines that are metabolized by a P450 isozyme subject to inhibition by their particular antidepressant.

Topics: Adolescent; Adult; Aged; Anti-Anxiety Agents; Antidepressive Agents; Automobile Driving; Benzamides; Benzodiazepines; Cytochrome P-450 Enzyme System; Depressive Disorder; Double-Blind Method; Drug Interactions; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Male; Middle Aged; Moclobemide; Monoamine Oxidase Inhibitors; Psychiatric Status Rating Scales; Psychomotor Performance; Time Factors

The influence of lithium on fluvoxamine therapeutic efficacy, plasma concentrations and pharmacokinetics was studied in 12 depressed inpatients. Six patients were on fluvoxamine monotherapy and six were on combined fluvoxamine-lithium therapy. The treatment response was determined using 17-item Hamilton Rating Scale for Depression. Blood samples were collected during 48 h after a single dose administration of 100 mg fluvoxamine, and five times at steady state after repeated doses of 100 mg fluvoxamine per day. The evaluation of 17-item Hamilton Rating Scale for Depression Scores showed a significant clinical improvement 2 and 4 weeks after the beginning of the therapy in both groups (p < 0.01). However, 2 weeks after the administration of the drug(s) had started, significant differences (p < 0.05) in efficacy between the two treatments in favour of the fluvoxamine-lithium combination were found. Plasma concentrations of fluvoxamine were measured by high-performance liquid chromatography. The comparison of the measured concentrations of fluvoxamine showed a similar course of the plasma concentration-time curves in both groups of patients. Pharmacokinetic parameters of fluvoxamine did not show any significant difference on the comparison between the groups. According to the results from this study, it is evident that lithium does not affect plasma concentrations and pharmacokinetics of fluvoxamine in depressed patients on concomitant treatment with these two drugs. However, the effect achieved with the combination was better.

Topics: Adult; Antidepressive Agents; Antidepressive Agents, Second-Generation; Area Under Curve; Biological Availability; Depressive Disorder; Drug Interactions; Drug Therapy, Combination; Female; Fluvoxamine; Half-Life; Humans; Lithium Carbonate; Male; Metabolic Clearance Rate; Middle Aged

Topics: Adolescent; Adult; Aged; Agoraphobia; Analysis of Variance; Behavior Therapy; Benzodiazepines; Combined Modality Therapy; Comorbidity; Depressive Disorder; Double-Blind Method; Fluvoxamine; Humans; Middle Aged; Panic Disorder; Personality Inventory; Placebos; Probability; Severity of Illness Index; Treatment Outcome

Topics: Adult; Depressive Disorder; Drug Administration Schedule; Female; Fluvoxamine; Follow-Up Studies; Humans; Male; Psychiatric Status Rating Scales; Recurrence; Selective Serotonin Reuptake Inhibitors; Time Factors; Treatment Outcome

The aim of this study was to evaluate the efficacy of fluvoxamine in the treatment of delusional depression.. Fifty-nine inpatients who met the DSM-III-R criteria for major depression with psychotic features were treated with fluvoxamine for 6 weeks. Patients were assessed at baseline and weekly thereafter with the Hamilton Depression Rating Scale and the Dimensions of Delusional Experience rating scale.. Of the 57 subjects completed the trial, 84.2% (N=48) recovered. The index episodes of the patients who did not respond to fluvoxamine were of significantly longer duration than those of the responders.. Fluvoxamine has a response rate similar to that of the currently most efficacious treatments for delusional depression, including antidepressants plus antipsychotics and ECT.

Topics: Age of Onset; Delusions; Depressive Disorder; Female; Fluvoxamine; Hospitalization; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Severity of Illness Index; Treatment Outcome

We evaluated the efficacy of a second serotonin selective reuptake inhibitor (SSRI) in patients who had failed to respond to the first SSRI used.. Fifty-five patients with major depression who had failed one of the SSRIs for their current depressive episode were included. After failing a trial of one SSRI, they received a second SSRI in an open clinical trial.. On the basis of the Clinical Global Impression-Improvement scale, 28 of 55 patients had a marked or complete antidepressant response.. These data provide preliminary clinical evidence that substituting a second SRI may be a useful clinical alternative in depressed patients who fail to respond to an adequate trial of an SSRI.

Topics: 1-Naphthylamine; Adult; Aged; Ambulatory Care; Depressive Disorder; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Paroxetine; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

Combination treatment with tricyclic antidepressants (TCAs) and serotonin selective reuptake inhibitors (SSRIs) is an increasingly employed strategy especially in depressed patients unresponsive to monotherapy. Comedications with SSRIs, however, may be hazardous owing to pharmacokinetic interactions that can result in elevated serum TCA levels. For the combinations, safety and tolerability data are lacking.. We report tolerability and safety of combined treatment with fluvoxamine and clomipramine (CMI) in 22 patients. Most patients suffered from depression and obsessive-compulsive symptoms. Diagnoses were made according to DSM-III-R criteria. Serum levels of CMI, N-desmethylclomipramine (DCMI), and 8-hydroxylated metabolites were determined. EEG, ECG, and laboratory parameters and adverse effects reported by the patients, as well as global clinical improvement, were assessed.. Generally, fluvoxamine/clomipramine comedication was well tolerated. Serum CMI levels reached 500 to 1200 ng/mL in half of the patients, while corresponding levels for DCMI and 8-hydroxylated metabolites were low. Moreover, the ratios of N-demethylation DCMI:CMI calculated from the ratios of drug concentrations in serum were markedly lower under comedication than under CMI monotherapy. Alterations in EEG, ECG, and laboratory parameters that had clinical relevance were rarely observed and were reversible after dose reduction of CMI. However, 2 patients developed myoclonic jerks. A majority of patients improved clinically during combination treatment. Clinically relevant side effects were absent in patients with serum CMI and DCMI levels below 450 ng/mL and ratios of N-demethylation below 0.3.. Our results suggest that comedication of fluvoxamine and clomipramine will result in markedly elevated serum clomipramine levels. Therefore, combination treatment with fluvoxamine and clomipramine should be carefully monitored by determination of serum levels of the TCA. Clinically, the pharmacokinetic interactions between fluvoxamine and clomipramine may be well tolerated in a majority of patients. However, in a few patients, higher serum levels may be associated with an increased risk of EEG changes and changes of intracardiac conductance. EEG and ECG should be used regularly to monitor comedicated patients.

Topics: Adult; Aged; Antidepressive Agents, Tricyclic; Clomipramine; Depressive Disorder; Dose-Response Relationship, Drug; Drug Monitoring; Drug Therapy, Combination; Electroencephalography; Female; Fluvoxamine; Humans; Male; Middle Aged; Obsessive-Compulsive Disorder; Selective Serotonin Reuptake Inhibitors

The efficacy and safety of fluvoxamine maleate, a selective serotonin reuptake inhibitor, was compared with placebo and imipramine in patients with major depressive disorder. Previous literature has cited a dose range of 100 to 300 mg/day of fluvoxamine maleate for the treatment of major depression; however, this study demonstrates that a dose range of 50 to 150 mg/day is as effective as imipramine (80-240 mg/day). After a 1- to 2-week, single-blind, placebo washout phase, 150 depressed outpatients were randomized to double-blind treatment with fluvoxamine maleate (50-150 mg/day), imipramine (80-240 mg/day), or placebo for 6 weeks. Fluvoxamine produced a significant therapeutic benefit over placebo (p < or = 0.05) as assessed by the total score on the Hamilton Rating Scale for Depression; imipramine (80-240 mg/day) produced similar results. The secondary outcome variables (i.e., Clinical Global Impression severity of illness item and 56-Item Hopkins Symptom Checklist depression factor) also showed significant differences between fluvoxamine maleate and placebo during three of the four final weeks of the study. Both fluvoxamine maleate and imipramine appeared to be safe and well tolerated by the majority of patients. As expected from the pharmacology of these agents, the imipramine groups reported more anticholinergic effects (dry mouth, dizziness, and urinary retention) and electrocardiographic effects, whereas the fluvoxamine group reported more nausea, somnolence, and abnormal ejaculation. The majority of these adverse events were mild to moderate and, with the exception of dry mouth (imipramine) and abnormal ejaculation (fluvoxamine), were transient. The data clearly demonstrate the antidepressant activity and tolerability of fluvoxamine maleate (50-150 mg/day) as compared with placebo; it is also as effective as the tricyclic antidepressant imipramine (80-240 mg/day) in patients with major depressive disorder.

Topics: Adult; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Personality Inventory; Treatment Outcome

The efficacy of fluvoxamine in the treatment of panic disorder complicated by depression was investigated in an 8-week, single-group, open-label, flexible-dose trial.. Seventeen patients having a principal diagnosis of panic disorder and scoring 16 or more on the 17-item Hamilton Rating Scale for Depression were treated with fluvoxamine at a mean final dose of 213 mg/ day. Outcome was assessed on measures of panic attacks, general and anticipatory anxiety, agoraphobic avoidance, depression, disability, and fear of anxiety symptoms.. Subjects improved on all measures except agoraphobic avoidance. Thirteen either chose to remain on fluvoxamine treatment after the study ended or resumed taking it after a brief period without medication or on another medication.. Fluvoxamine appears to be effective in this population.

Topics: Adult; Agoraphobia; Depressive Disorder; Drug Administration Schedule; Family Practice; Female; Fluvoxamine; Humans; Male; Middle Aged; Panic Disorder; Psychiatric Status Rating Scales; Treatment Outcome

Serotonergic agents appear to be effective treatments for premenstrual symptoms in a number of small trials. The purpose of this open-label treatment study was to collect pilot information on the efficacy of fluvoxamine for premenstrual dysphoric disorder (PDD).. Twelve women who sought medical treatment for premenstrual symptoms were evaluated. The main outcome measure was the premenstrual score from daily symptom reports (DSRs) maintained by the subjects. After a 2-month screening period, 10 subjects who met DSM-IV criteria for PDD were treated with fluvoxamine taken daily for two menstrual cycles. The mean dose at 4 weeks was 85 mg/day; at 8 weeks, all subjects took 100 mg/day.. The mean premenstrual DSR scores improved at 4 weeks from the pretreatment baseline (paired t test, p < .0008) and remained improved at 8 weeks at approximately the same level (p < .003). Symptoms with the greatest improvement (p < .003, significant with the Bonferroni adjustment) were irritability, anxiety, feeling out of control, and decreased interest in usual activity. Sixty percent (6/10) of the subjects reported at least a 50% reduction in the DSR scores, a conservative clinical definition of improvement. The mean premenstrual Hamilton Rating Scale for Depression scores decreased from 19 at the pretreatment baseline to 9 at the 4-week evaluation. The main side effects were insomnia (N = 6), fatigue (N = 4), dry mouth (N = 4), and nausea (N = 3) and were generally mild and transient.. These promising pilot data show the importance of a controlled trial over a longer time period to provide definitive information on the efficacy of fluvoxamine for premenstrual dysphoric disorder.

Topics: Adolescent; Adult; Depressive Disorder; Drug Administration Schedule; Fatigue; Female; Fluvoxamine; Humans; Menstrual Cycle; Middle Aged; Nausea; Pilot Projects; Premenstrual Syndrome; Psychiatric Status Rating Scales; Severity of Illness Index; Sleep Initiation and Maintenance Disorders; Treatment Outcome

A 10-week open-label trial of fluvoxamine was conducted for male Vietnam combat veterans with chronic PTSD. Subjects were excluded if they met full current criteria for panic disorder or agoraphobia, and lifetime criteria for psychosis, bipolar disorder, or organic mental syndrome. Repeated MANOVA was performed to determine change over time. Fluvoxamine was well tolerated; side effects were observed primarily early in treatment with headache, insomnia, sedation, and gastrointestinal distress being most frequent. Fluvoxamine was effective for treating the core intrusion, avoidance, and arousal symptoms of PTSD. Large treatment effects were seen by 4-6 weeks, and maintained at 10 weeks. The magnitude of change was greater than has been previously reported for antidepressant treatment of male Vietnam combat veterans with PTSD.

Topics: Ambulatory Care; Combat Disorders; Comorbidity; Depressive Disorder; Fluvoxamine; Humans; Male; Mental Disorders; Middle Aged; Psychiatric Status Rating Scales; Treatment Outcome; Veterans; Vietnam

Approximately 20 million patients suffer from major depressive disorder each year, indicating a need for antidepressant agents that are synonymous with effectiveness, tolerability and patient compliance. The authors examined the effects of fluvoxamine, a selective serotonin reuptake inhibitor, in the treatment of outpatients meeting DSM-III-R criteria for major depressive disorder. A randomized, double-blind, parallel group, placebo- and imipramine-controlled single center study was conducted in 150 outpatients. Patients were randomized to receive up to 150 mg/day of fluvoxamine as a single bedtime dose, 240 mg/day of imipramine on a twice-daily (BID) schedule, or placebo for six weeks. Efficacy measurements included HAM-D, MADRS, CGI, Raskin-Covi and SCL-56 scales. The HAM-D total score indicated that both active treatment groups showed significantly (p < or = 0.05) greater therapeutic benefit than did placebo. Severely depressed patients (HAM-D > or = 30) responded better to fluvoxamine in five of six measures. Side-effects from fluvoxamine were similar to those reported for other selective serotonin reuptake inhibitors (nausea, somnolence) and were well tolerated. Imipramine was associated with anticholinergic effects such as dry mouth and dizziness. The pharmacokinetic properties of fluvoxamine which allow the drug to be administered as a single daily dose should aid in the maintenance of patient compliance, while offering significant clinical benefit in the improvement of depressive symptoms.

Topics: Adrenergic Uptake Inhibitors; Adult; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Constipation; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Nausea; Selective Serotonin Reuptake Inhibitors

This randomized, double-blind, parallel-group design study of 100 outpatients with major depressive disorder is the first study in the United States to compare the efficacy and tolerability of fluvoxamine (100-150 mg/day) and fluoxetine (20-80 mg/day). After a variable, single-blind, washout period, patients were randomized to receive either fluvoxamine (51 patients) of fluoxetine (49 patients) for 7 weeks. Efficacy was assessed with the 21-item Hamilton Rating Scale for Depression (HAM-D), and Clinical Global Impressions scale for severity and improvement. Eighty-four percent of each treatment group completed the study with each group having a mean score at end point of less than 10. Both groups demonstrated a 60% improvement in HAM-D scores over the 7-week trial. There were no statistically significant differences observed between the two groups on any efficacy parameter. The medications were well tolerated, with only two patients in each group who were terminated because of side effects. There were differences in the side-effect profiles, with fluvoxamine being associated with less nausea than fluoxetine. In summary, fluvoxamine and fluoxetine were equally effective in reducing depressive symptoms, but the two drugs displayed slightly different side-effect profiles.

Topics: Adult; Antidepressive Agents, Second-Generation; Anxiety; Depressive Disorder; Double-Blind Method; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Nausea; Selective Serotonin Reuptake Inhibitors

This 7- to 8-week, multicenter, randomized, double-blind, placebo-controlled study was performed to determine the dose-effect relationship and minimum effective dose for fluvoxamine maleate in a titrated fixed-dose study of major depressive disorder. Gradual titration over 2 weeks to fixed maintenance doses was employed to minimize dropout due to initial side effects. The study enrolled 600 outpatients, male and female, age 18-65, meeting DSM-III-R criteria for major depressive disorder. A 13-item subscore of the standard 21-Item Hamilton Depression Scale was used to minimize the possible contribution of known side effects from serotonin reuptake inhibitors to the overall HAM-D score. Secondary efficacy assessments included the HAM-D retardation factor, HAM-D depressed mood item, CGI-severity of illness item, and SCL depression factor. Fluvoxamine (50-150 mg/day) was therapeutically effective and well tolerated during 6 weeks of therapy. Based on the HAM-D depressed mood item, efficacy was dose dependent. The minimum effective dose was 50 mg/day. Fluvoxamine maleate shows dose-related effectiveness in the acute treatment of major depressive disorder.

Topics: Administration, Oral; Adolescent; Adult; Aged; Analysis of Variance; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluvoxamine; Humans; Longitudinal Studies; Male; Middle Aged; Patient Dropouts; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Time Factors

In 16 depression clinics in hospitals and outpatient facilities in the Netherlands, a study was performed to evaluate and compare the efficacy and tolerability of citalopram and fluvoxamine and to determine the difference in the incidence of gastrointestinal side-effects. A total of 217 patients with a depressive disorder (DSM-III-R criteria) and a score of at least 16 on the Hamilton rating scale for depression were randomized to treatment. The results of this study indicate that the two drugs are equally effective. The adverse events occurring during treatment show a similar pattern between the two drugs, but citalopram is better tolerated than fluvoxamine. Citalopram induces fewer gastrointestinal adverse events compared with fluvoxamine. However, this did not affect the drop-out rates.

Topics: Adult; Antidepressive Agents; Citalopram; Depressive Disorder; Diarrhea; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Nausea; Outpatients; Paresthesia; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors

The effect of comedication with fluvoxamine on the plasma concentrations of the enantiomers of citalopram and its metabolites in dextromethorphan/mephenytoin phenotyped patients pretreated with citalopram (CIT) was studied: seven female patients (45.1 +/- 13.9 years) suffering from a major depressive episode [ICD-10: F32.2 (n = 3 patients), F33.2 (n = 2), F32.10 (n = 1) or F32.11 (n = 1)], who were non-responders to a 3-week treatment with 40 mg/day CIT (From day-21 to day 0) (day 0: MADRS score > or = 12), were co-medicated for another 3 weeks with fluvoxamine (50 mg/day from day 1-7, 100 mg/day from day 14-21). All patients were extensive metabolizers of mephenytoin (CYP2C19) and dextromethorphan (CYP2D6), except one patient, who had a genetic deficiency of CYP2D6. There was a significant increase of the plasma concentrations of S- and R-citalopram from day 0 (27 +/- 14 micrograms/l and 55 +/- 23 micrograms/l, respectively) to day 21 (83 +/- 38 micrograms/l and 98 +/- 44 micrograms/l, respectively), after addition of fluvoxamine (P < 0.02, for each comparison), and the mean ratio S/R-citalopram increased from 0.48 to 0.84. S-Citalopram inhibits more potently 5-HT uptake than R-citalopram: therefore, fluvoxamine increases the pharmacologically more active S-citalopram with some stereoselectivity. According to a previous in vitro study, this pharmacokinetic interaction occurs on the level of CYP2C19, but also of CYP2D6 and CYP3A4 which, in contrast to CYP1A2, contribute to the N-demethylation of citalopram and which are stereoselectively inhibited by fluvoxamine. All but one patient showed clinical improvement by a decrease of the MADRS score by at least 50% and a final score < or = 13 (mean +/- SD: day 0:30.6 +/- 9.2; day 21:11.0 +/- 6.5). Some patients showed minor symptoms, such as nausea and tremor, but the combined treatment was generally well tolerated.

Topics: Adult; Antidepressive Agents; Citalopram; Depressive Disorder; Drug Resistance; Drug Synergism; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Middle Aged; Nausea; Selective Serotonin Reuptake Inhibitors; Tremor

Suicide is a serious risk factor in major depressive disorder. Paradoxical emergence of suicidal ideation or behavior during antidepressant treatment has been reported in isolated cases. An evaluation was undertaken to assess the risk of suicidality during treatment with fluvoxamine, a serotonin selective reuptake inhibitor.. Meta-analyses were conducted on pooled data from double-blind, randomized, placebo-controlled, parallel-group clinical trials. The primary outcome measure was the suicide item of the Hamilton Rating Scale for Depression. Tests for emergence of substantial suicidal ideation and improvement or worsening in suicidal ideation were performed using the Mantel-Haenszel adjusted incidence difference. The Breslow-Day test was used to test for lack of homogeneity across trials. Secondary analysis, which consisted of Pearson's chi-square test, was used to confirm the Mantel-Haenszel result.. In comparison to placebo, fluvoxamine was associated with significantly greater improvement in suicidal ideation (p = .01) and significantly less worsening of suicidal ideation (p < .01). No differences were found in the emergence of substantial suicidal ideation.. These findings demonstrate that fluvoxamine is not associated with an increased risk of emergence of substantial suicidal thoughts among depressed patients. On the contrary, the results are suggestive of a protective effect of fluvoxamine upon the risk of suicidal ideation.

Topics: Adult; Antidepressive Agents, Tricyclic; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Risk Factors; Selective Serotonin Reuptake Inhibitors; Suicide; Suicide, Attempted

Fluvoxamine belongs to the class of selective serotonin reuptake inhibitors (SSRIs) which have recently gained large popularity as antidepressant agents essentially because they lack the most troublesome adverse effects of older antidepressants (i.e. tricyclic antidepressants) such as anticholinergic effects and cardiotoxicity. Recent studies in the literature suggest that HIV-1 infected subjects are affected by depressive episodes with a relatively high frequency, often requiring an antidepressant treatment. Due to its favorable adverse effects profile, we used fluvoxamine as first line treatment for sixteen depressed HIV-1 infected subjects. They were administered the drug at a daily dosage of 100 mg in the evening. Fluvoxamine provided a good clinical efficacy for six of these patients, whereas the other ten had to discontinue the drug because of the presence of severe adverse effects such as acute total insomnia, gastro-intestinal disturbances together with anorexia, aggressive and impulsive behavior and excessive sedation. The observed fluvoxamine side-effects are not typical or specific for this particular patient group since they are also described in seronegative subjects taking fluvoxamine; however, our findings seem to indicate that they become more frequent and more severe when the drug is administered to HIV-1 infected patients.

Topics: Adult; Antidepressive Agents, Second-Generation; Depressive Disorder; Female; Fluvoxamine; HIV Infections; HIV-1; Humans; Male; Psychiatric Status Rating Scales

In this investigation, the antidepressant efficacy of fluvoxamine and imipramine was compared in a randomized, double-blind, placebo-controlled study lasting 4 weeks; 338 depressed patients were recruited at five North American centres. For the efficacy analyses an intent-to-treat sample was defined. The global efficacy of the two drugs was assessed by the Hamilton Depression scale (HAM-D) and Clinical Global Impression (CGI) scores. Antidepressant activity was also assessed using the percentage of responders on the CGI "improvement" scale. In addition the time of onset of antidepressant effect was evaluated by weekly analysis of individual HAM-D items. The intent-to-treat sample was stratified retrospectively according to the severity of the depression (mild, moderate or severe). Regarding global efficacy, compared with placebo, only fluvoxamine significantly improved the HAM-D total scores at Week 4 (p < 0.05). There was a suggestion from individual HAM-D item scores (depressed mood, suicide, psychic anxiety) that fluvoxamine had an earlier effect than imipramine. Overall, compared with placebo, more HAM-D items were improved by fluvoxamine than imipramine. Fluvoxamine but not imipramine was significantly superior to placebo in severely depressed patients as shown by improvements in the HAM-D score (p < 0.01) and the CGI "improvement" score (p < 0.05). Side effect profiles for the active agents were typical for their pharmacological category:imipramine was associated with anticholinergic effects, particularly dry mouth, and fluvoxamine was associated with nausea and vomiting.

Topics: Adult; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Placebos; Psychiatric Status Rating Scales; Retrospective Studies; Severity of Illness Index; Treatment Outcome

In an open multicentre study designed to closely reflect the clinical situation, 315 out-patients diagnosed by their psychiatrist as having depression and/or obsessive-compulsive disorder (OCD), and/or panic disorder, were treated for 12 weeks with fluvoxamine (100-300 mg/day). Twelve weeks of fluvoxamine therapy was completed by 229 (73%) patients. Longer illness duration prior to treatment was associated with a significantly reduced rate of treatment withdrawal, whereas a diagnosis of OCD was predictive of treatment withdrawal. The main reasons patients discontinued fluvoxamine therapy were adverse effects experienced before Week 8, and clinical improvement thereafter. Age, sex, and diagnosis had no predictive value for treatment outcome; however, psychiatric antecedents and duration and severity of illness at baseline were significant predictors of disease severity at endpoint. Fluvoxamine decreased both the frequency and severity of baseline symptoms, with improvement continuing for the duration of the study. Nausea was the only symptom to show an initial increase in frequency and severity, but this subsided after 4 weeks to levels below baseline frequency and severity.

Topics: Adult; Affect; Ambulatory Care; Anxiety Disorders; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Middle Aged; Obsessive-Compulsive Disorder; Panic Disorder; Patient Compliance; Prevalence; Treatment Outcome

The in vivo pharmacokinetic interaction between two selective serotonin reuptake inhibitors (SSRI) (fluvoxamine, fluoxetine) and tricyclic antidepressants (TCAs) (amitriptyline, clomipramine) or neuroleptics (haloperidol, cyamemazine, levomepromazine, propericiazine) was assessed in 29 in-patients. They were phenotyped twice with dextromethorphan and mephenytoin: first in steady state conditions while under treatment with TCAs or neuroleptics; and also 10 days after an associated treatment with fluvoxamine (150 mg day(-1)) or fluoxetine (20 mg day(-1)). A clear and statistically significant increase in the mean urinary metabolic ratio (MR) of dextromethorphan/dextrorphan and in the mean mephenytoin S/R ratio (S/R) was seen with the fluvoxamine and fluoxetine treatment. The mean MR increased from 0.13 to 0.27 (P<0.01) with fluoxetine and from 0.34 to 0.84 with fluvoxamine (P<0.05). The (dextromethorphan) 'extensive metabolizer' phenotype switched to the 'poor metabolizer' phenotype in six patients by the 10-day fluoxetine treatment, and in two patients by the fluvoxamine treatment. The mean S/R increased from 0.24 to 0.34 (P<0.05) with fluoxetine, and from 0.33 to 0.58 (P<0.002) with fluvoxamine. These results are in agreement with the observed modification of TCA plasma levels after the SSRI association. During fluvoxamine treatment, amitriptyline and clomipramine plasma levels (P<0.06 both) tendentially increased, and those of demethylclomiprarnine decreased (P<0.06). Fluoxetine addition lead to a significant increase (P<0.02) of the desmethylclomipramine plasma levels. Fluvoxamine induced a moderate augmentation of the plasma levels of haloperidol and its reduced metabolite and no change in the plasma levels of cyamemazine and levomepromazine. But patients treated with neuroleptics are to few to draw any firm conclusion. This study suggests, that fluoxetine and fluvoxamine differ in their interaction with the metabolism of some other basic psychotropic drugs, by a mechanism which implies CYP2D6 and CYPmeph and possibly other isoformes of cytochrome P-450. Moreover, the interactions produced varied with the TCA prescribed.

Topics: Adult; Amitriptyline; Antipsychotic Agents; Clomipramine; Depressive Disorder; Drug Interactions; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Pharmacogenetics; Phenotype

The authors studied 75 outpatients with DSM-III-R panic disorder who had participated in a clinical trial and had been randomly assigned to receive fluvoxamine, cognitive therapy, or placebo for an 8-week period. They compared a group with high levels of depressive symptoms and a group with low levels of depressive symptoms. At baseline, patients with high levels of depressive symptoms were more likely to have severe phobic avoidance and to have higher scores on measures of anxiety, hyochondriasis, and disability. An important finding was that depressive symptoms improved at a rate which paralleled improvement in panic and anxiety. Likewise, the presence of depressive symptoms did not interfere with treatment response in panic disorder. Clinical implications of the findings are discussed.

Topics: Adult; Ambulatory Care; Antidepressive Agents; Cognitive Behavioral Therapy; Combined Modality Therapy; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Panic Disorder; Placebos; Psychiatric Status Rating Scales; Treatment Outcome

In the choice of an antidepressant drug the clinician must often consider the presence of a cardiovascular comorbidity in depressed patients. In the present study the cardiovascular effects of fluvoxamine and maprotiline were compared in a double-blind trial in which the quantitative changes in ECGs were assessed before and during a 3-week treatment. A total of 33 patients (mean age 44 years; range 20-65 years) with major depressive disorder (RDC) who were free from clinically relevant organic diseases were investigated. After a 7-day wash-out period, a 3 week treatment phase was started with 200 mg daily of either fluvoxamine (n = 18) or maprotiline (n = 15). On days 0, 7, 14 and 21 a 12-lead standard ECG was performed and the drug plasma levels were determined. All ECGs were analysed in a blind fashion by an internist. Maprotiline caused a significant prolongation of the PR interval (P < 0.001) and of the QRS interval (P < 0.01) was well as an increase in heart rate (P < 0.001). The QTc interval was only tendentially prolonged (P < 0.10) and the P-wave duration and T-wave amplitude were not affected by maprotiline. No significant changes in ECG parameters were observed during treatment with fluvoxamine; and there was a nonsignificant trend (P < 0.10) for a lower heart rate during treatment. Blood pressure was not affected by treatment with either antidepressant. In both groups no significant correlations were found between ECG findings and the plasma levels of the drugs. Our results confirm that fluvoxamine in therapeutic dose causes no alteration in surface ECG regarding cardiac conduction and repolarization. Conversely, maprotiline caused a significant prolongation of atrioventricular and intraventricular conduction and a rise in heart rate. Although these effects were not clinically relevant in our sample of patients without overt heart disease, they should be taken into account when treating depressed patients with concomitant cardiac disease.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Blood Pressure; Depressive Disorder; Double-Blind Method; Electrocardiography; Female; Fluvoxamine; Heart Rate; Hemodynamics; Humans; Male; Maprotiline; Middle Aged

Fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is used to treat depression. No significant effect on the electrocardiogram (ECG) has been reported during short-term controlled studies of SSRI's. We report a long-term (1 year) multi-center, double-blind controlled study of the ECG during treatment of depression with fluvoxamine (FX), active control medication (TCA), and placebo (PLA).. Initially ECGs were obtained from 1840 physically healthy, depressed outpatients who were treated with FX, TCA, or PLA for 6 weeks. A subset of these patients continued treatment for up to one year. Complete sets of ECGs were obtained from 462 of these patients. Patients whose depression was substantially improved in the initial 6-week study ("responder") received the same medication. Non-responders received a blinded active medication. Pre-treatment, intra-study, and past-treatment ECGs were recorded according to protocol. One blinded electrocardiographer measured and analyzed all ECG data. The effects of each medication upon the ECG were measured and compared.. Of the 462 patients, 311 used FX, 100 used TCA and 51 used PLA. Analyses of ECG data for each treatment focused on changes in ECG measurements; % of normal ECGs, and % of individual ECG findings. The ECG changes during FX treatment were less than or not significantly different from the ECG changes with PLA treatment. The changes with TCA were as expected.. Fluvoxamine treatment of depression for one year was not associated with any significant effect on the ECG.

Topics: Adolescent; Adult; Aged; Antidepressive Agents, Second-Generation; Depressive Disorder; Electrocardiography; Female; Fluvoxamine; Humans; Male; Middle Aged

Topics: Adult; Analysis of Variance; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Thyroid Gland; Thyroid Hormones

A total of 32 unmedicated patients with episodes of major depression (DSM-III-R) and 32 normal control subjects matched for age and sex were tested for heart rate variability (R-R variation) while resting and during deep breathing. Compared with the group of healthy subjects, the depressed patients showed no abnormalities before therapy. The patients were randomly allocated for treatment with 150 mg of amitriptyline per day (N = 8), 150 mg of doxepin per day (N = 8), 150 mg of fluvoxamine per day (N = 8), and 20 mg of paroxetine per day (N = 8). During treatment with either amitriptyline or doxepin, the coefficients of variation at rest and during deep breathing, which are largely independent of heart rate, had significantly decreased after 14 days (p = 0.012), whereas patients treated with fluvoxamine or paroxetine showed no significant changes of heart rate variability parameters after 14 days. The implications of these findings are discussed.

Topics: Adult; Aged; Amitriptyline; Depressive Disorder; Dose-Response Relationship, Drug; Doxepin; Drug Administration Schedule; Electrocardiography; Female; Fluvoxamine; Heart Rate; Humans; Male; Middle Aged; Paroxetine

The authors compared rates of new episodes in a sample of 64 unipolar subjects treated with fluvoxamine (n = 32) and lithium (n = 32) during a follow-up period of 24 months. Unipolar patients on lithium treatment had a worse outcome with a higher frequency of new recurrences compared with of new recurrences compared with patients on fluvoxamine during the course of preventive treatment.

Topics: Adult; Aged; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluvoxamine; Follow-Up Studies; Humans; Lithium Carbonate; Long-Term Care; Male; Middle Aged; Personality Inventory; Recurrence; Treatment Outcome

1. Intent-to-treat analysis of a parallel, double-blind comparative study of fluvoxamine, imipramine and placebo in patients with major depressive episode (DSM III). 2. A posteriori the patients have been stratified in three severity groups on basis of their initial HAMD-score: Mild depression (15-20), Moderate depression (21-25) and Severe depression (> or = 26). 3. At endpoint both the decrease in HAMD-scores and the percentage responders (CGI 1-2) differed significantly comparing fluvoxamine with placebo and tended to differ significantly comparing with imipramine in the severely depressed patients. 4. The results with fluvoxamine in severely depressed patients were better than in moderately depressed patients, which in turn were better than in mildly depressed patients. 5. Despite a lower daily fluvoxamine dosage in the mild group, the premature terminator rate in this group (47%) was higher than in the moderate group (27%) or in the severe group (24%). With placebo the situation was opposite. More patients (47%) terminated before day 28 in the severe group, compared to the moderate (32%) and the mild group (24%), while on placebo. 6. The majority of responders to fluvoxamine at endpoint, showed already improvement at week 1 (82.5%).

Topics: Adult; Aged; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales

The molar ratio of total plasma tryptophan (Trp) to the sum of the other large neutral amino acids (LNAAs), thought to reflect brain serotonin (5-HT) formation, was estimated in 47 patients with major depression (unipolar and bipolar) before and after 6 weeks of treatment with a serotonin uptake inhibitor, fluvoxamine. We found a significant difference between responders (n = 39) and nonresponders (n = 8) for the pre- and in-treatment plasma Trp to LNAAs ratios. In contrast, there were no differences between the two groups for the mean plasma steady-state fluvoxamine levels. These findings suggest that a specific plasma amino acid profile may be a useful indicator of good clinical response to a selective 5-HT uptake inhibitor.

Topics: Adult; Aged; Amino Acids; Bipolar Disorder; Depressive Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluvoxamine; Humans; Male; Middle Aged; Personality Inventory; Tryptophan

To determine the efficacy and safety of a serotonin selective reuptake inhibitor (SSRI) combined with moclobemide in the treatment of 11 patients with various DSM-III-R diagnoses.. Subjects received moclobemide in doses of 150 to 800 mg/day together with sertraline (N = 5) in doses of 25 to 200 mg/day or fluvoxamine (N = 6) in doses of 50 to 200 mg/day. Patients were carefully monitored for side effects and for clinical response at the end of the trial, which lasted a minimum of 5 weeks.. The combination was tolerated extremely well. Insomnia was the most common side effect, occurring in 5 of 11 subjects. A marked or complete therapeutic response was noted in 8 of 11 subjects.. This open clinical trial suggests that combined SSRI-moclobemide treatment appears to be safe and well tolerated. It may also have therapeutic effects in treatment-refractory patients.

Topics: 1-Naphthylamine; Adult; Benzamides; Depressive Disorder; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Male; Mental Disorders; Middle Aged; Moclobemide; Monoamine Oxidase Inhibitors; Obsessive-Compulsive Disorder; Panic Disorder; Selective Serotonin Reuptake Inhibitors; Sertraline

Bidirectional drug interactions between fluvoxamine and classical antidepressants were studied in depressed patients. A column switching technique combined with high performance liquid chromatography (HPLC) enabled automated analyses of plasma for simultaneous determination of fluvoxamine, tricyclic and tetracyclic antidepressants and demethylated and major hydroxylated metabolites in a single HPLC run. The measurements revealed that fluvoxamine inhibited N-demethylation of imipramine, clomipramine, amitriptyline and maprotiline whereas interferences with hydroxylation reactions were restricted to aromatic 8-hydroxylation of clomipramine. In patients under fluvoxamine monotherapy before comedication, plasma concentrations of fluvoxamine increased after administration of a tricyclic antidepressant, thus indicating bidirectional drug interactions. The inhibitory effects of fluvoxamine on the metabolism of classical antidepressants disappeared after discontinuation of concomitant fluvoxamine treatment within at least 1-2 weeks. The reported alterations in drug metabolism observed in depressed patients who were under fluvoxamine/tricyclic antidepressant comedication suggested that careful supervision and regular drug monitoring are necessary in such patients.

Topics: Adult; Antidepressive Agents; Chromatography, High Pressure Liquid; Dealkylation; Depressive Disorder; Female; Fluvoxamine; Humans; Hydroxylation; Male; Middle Aged; Spectrophotometry, Ultraviolet

Sixty outpatients with obsessive-compulsive disorder (OCD, 22 men, 38 women) were randomized to receive 6 months of antiexposure therapy with fluvoxamine (group F), exposure therapy with fluvoxamine (group Fe), or exposure therapy with placebo (group Pe). Patients in group F did not comply with antiexposure therapy, so it was in fact a neutral condition. Patients began with depressed mood (mean Hamilton depression score = 19). Fifty patients were reevaluated at week 8, 44 at week 24 (posttest), 37 at week 48, and 33 at 18 months, 1 year posttreatment (group F, n = 10; group Fe, n = 12; group Pe, n = 11). The three groups improved on rituals and depression. There was a drug effect on rituals at week 8 and on depression at week 24; both these effects disappeared at week 48. The 33 18-month completers had been comparable at baseline to those not followed up, apart from having more severe behavioral avoidance. At 18-month followup, patients as a whole remained improved with no between-group differences; over 80% of the Fe and Pe patients versus 40% of the F patients were not receiving antidepressant treatment (Fe vs. F: p < 0.04; Pe vs. F: p = 0.053; Fe vs. Pe: NS). In OCD fluvoxamine and exposure therapy were synergistic in the short term, and exposure reduced subsequent need for antidepressants in the followup year after they had been stopped.

Topics: Adult; Behavior Therapy; Combined Modality Therapy; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Follow-Up Studies; Humans; Male; Middle Aged; Obsessive-Compulsive Disorder; Personality Inventory; Single-Blind Method; Treatment Outcome

This retrospective case-controlled analysis evaluated treatment response to the serotonin reuptake inhibitor fluvoxamine in patients with obsessive-compulsive disorder (OCD), with or without a comorbid chronic tic disorder. Thirty-three fluvoxamine-treated OCD patients with a concurrent chronic tic disorder were compared with 33 age- and sex-matched OCD patients without chronic tics who had received fluvoxamine treatment in the same setting during the same period of time and in a similar manner. Although both groups of patients demonstrated statistically significant reductions in obsessive-compulsive, depressive, and anxiety symptoms with fluvoxamine treatment, the frequency and magnitude of response of obsessive-compulsive symptoms was significantly different between the two groups. A clinically meaningful improvement in obsessive-compulsive symptoms occurred in only 21% of OCD patients with comorbid chronic tics compared with a 52% response rate in OCD patients without chronic tics. Moreover, OCD patients with a concurrent chronic tic disorder showed only a 17% reduction in Yale-Brown Obsessive-Compulsive Scale scores compared with a 32% decrease in the severity of obsessive-compulsive symptoms in those OCD patients without chronic tics. These results suggest that serotonin reuptake inhibitor monotherapy may be less efficacious for improving obsessive-compulsive symptoms in OCD patients with than without tics. Combined with differences in the clinical phenomenology between these two groups, these treatment response data support the hypothesis that OCD patients with a comorbid chronic tic disorder may be a clinically meaningful subtype.

Topics: Adult; Comorbidity; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Obsessive-Compulsive Disorder; Retrospective Studies; Single-Blind Method; Tic Disorders; Tourette Syndrome

The data presented represent cardiovascular parameters collected from one site of a larger, multicenter, double-blind, placebo-controlled, 6-week outpatient efficacy study of the serotonin uptake inhibitor fluvoxamine in depressed outpatients.. In this smaller study, we compared fluvoxamine (N = 17) to the prototypic antidepressant, imipramine (N = 14), and to placebo (N = 15). Specific parameters investigated were drug effects on postural pulse and blood pressure changes and ECG parameters including PR, QRS, and QTc intervals and ventricular heart rate.. Fluvoxamine had few effects on measured parameters. Imipramine produced statistically significant changes on all measures; placebo had no effects on cardiac measures.. Our data support that fluvoxamine, in a sample of healthy depressed outpatients, has little effect on cardiovascular function. Further study and clinical experience with this drug will be necessary before the full extent of its cardiac profile is known.

Topics: Adult; Aged; Blood Pressure; Cardiovascular Physiological Phenomena; Cardiovascular System; Depressive Disorder; Electrocardiography; Female; Fluvoxamine; Heart Rate; Humans; Hypotension, Orthostatic; Imipramine; Male; Middle Aged; Placebos; Pulse

We evaluated the efficacy of buspirone in the augmentation of antidepressant response to the serotonin reuptake inhibitors.. Twenty-five patients with major depressive disorder who had failed several previous treatments for their current depressive episode were included. After failing a trial of fluoxetine or fluvoxamine, they received buspirone in addition to the serotonin reuptake inhibitor for 3 weeks in an open clinical trial.. Seventeen of 25 patients had a marked or complete antidepressant response.. These data provide clinical evidence suggesting that buspirone augmentation may be useful clinical alternative in depressed patients who fail to respond to a serotonin reuptake inhibitor.

Topics: Adult; Ambulatory Care; Buspirone; Depressive Disorder; Desipramine; Drug Therapy, Combination; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Selective Serotonin Reuptake Inhibitors

The authors found that buspirone added to the treatment of 33 patients with obsessive-compulsive disorder who were refractory to the serotonin reuptake inhibitor fluvoxamine was no better than placebo in reducing obsessive-compulsive, depressive, or anxiety symptoms. This finding suggests that addition of buspirone to ongoing fluvoxamine therapy is not an effective treatment strategy for most patients with obsessive-compulsive disorder.

Topics: Adult; Anxiety Disorders; Buspirone; Depressive Disorder; Double-Blind Method; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Male; Obsessive-Compulsive Disorder; Placebos; Psychiatric Status Rating Scales

We examined the relationship between plasma concentrations of specific acting antidepressants (fluvoxamine/maprotiline) and clinical improvement as well as the impact of the magnitude of the plasma concentration of these antidepressants on side effects. Patients (32 patients with major depression) were treated within a double-blind parallel trial for four weeks and plasma concentrations were obtained before, on days 8 and 28 of the trial. Although there was a fixed-flexible dosage design it was apparent that 16 patients (89%) of the fluvoxamine group and all patients of the maprotiline group received a dosage between 200 and 300 mg/day in the last week of the trial. Plasma concentrations (mean +/- SD micrograms/l) of fluvoxamine were 125 +/- 91 and 142 +/- 108 on days 8 and 28, respectively and the range of fluvoxamine plasma concentrations on day 28 was from 20 to 417 micrograms/l. Plasma concentrations (mean +/- SD micrograms/l) of maprotiline were 146 +/- 62 and 202 +/- 134 on days 8 and 28, respectively and the range of maprotiline plasma concentration on day 28 was from 12 to 428 micrograms/l. There was no linear relationship between plasma concentrations of both antidepressants (fluvoxamine/maprotiline) and oral dosage. Whereas there was no correlation between fluvoxamine concentration and clinical response there was a tendency that higher maprotiline concentrations were associated with a better antidepressive efficacy at the end of the trial. Higher concentrations of fluvoxamine as well as of maprotiline were significantly (P < 0.05) associated with more side effects.

Topics: Adult; Analysis of Variance; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Maprotiline; Middle Aged; Psychiatric Status Rating Scales

The efficacy of fluvoxamine was compared to that of amitriptyline in a double-blind 6-week fixed-dose trial of 56 inpatients with major depressive episode. The two drugs were comparable in their antidepressant efficacy. We tested the percentage of improvement in Hamilton-D scores during the first and the second weeks of treatment as predictors of efficacy for the last week. Improvement rates during the second week significantly predicted the outcome. We also investigated whether or not some symptomatological characteristics would permit prior prediction of the outcome with amitriptyline or fluvoxamine, dividing our sample into responders and nonresponders to the two drugs. The four groups showed differences in their symptomatological profiles.

Topics: Adult; Aged; Amitriptyline; Bipolar Disorder; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Personality Inventory; Recurrence

A series of double-blind hospital based studies comparing fluvoxamine with other antidepressants in depressed patients is reviewed. Overall there were no significant differences in terms of efficacy between fluvoxamine and the comparators (amitriptyline, dothiepin, lofepramine and mianserin). Fluvoxamine was shown to be associated with a low incidence of anticholinergic, cardiovascular or sedative effects. This profile of activity, together with low toxicity in overdosage, has established the place of fluvoxamine in the treatment of depressive illness.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents, Tricyclic; Body Weight; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged

The efficacy and tolerability of moclobemide and fluvoxamine, two new types of antidepressant agents, were compared in a multicentre, double-blind prospective study of patients with a diagnosis of major depressive episode (DSM III). Patients were randomized to receive either moclobemide (150 mg) or fluvoxamine (50 mg) twice daily for 7 days, immediately following a washout period of at least 1 week. Dosages were increased where necessary on day 8, to a maximum of moclobemide 450 mg or fluvoxamine 200 mg and in most cases were maintained at these levels for the remainder of the study period (4-6 weeks). Both treatment groups showed a marked antidepressant effect. While both treatments were well tolerated, moclobemide showed a more favourable side-effect profile than fluvoxamine. Of the 126 patients eligible for evaluation, 34 withdrew from therapy, 22% in the moclobemide group and 30% in the fluvoxamine group. Adverse events were reported in 41.8% of patients treated with moclobemide compared to 60.3% of patients in the fluvoxamine group. Reports of dry mouth and other anticholinergic effects were more frequent among those treated with fluvoxamine. A greater number of gastrointestinal complaints, especially nausea, also occurred in the fluvoxamine-treated patients.

Topics: Adult; Antidepressive Agents; Benzamides; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; France; Humans; Male; Moclobemide; Switzerland

The study of a sample of 189 inpatients with the diagnostic of Major Depressive Disorder (DSM III-R) treated with fluvoxamine showed: a good compromise efficacy/tolerance in 75% of cases; an interruption of treatment in 25% of cases, schematically divided in early gastric intolerance and in late resistance. 2.5% of manic switches have been observed and contribued, with this pattern of good results, to confirm the major antidepressant activity and good tolerance of fluvoxamine.

Topics: Bipolar Disorder; Depressive Disorder; Fluvoxamine; Hospitalization; Humans; Time Factors

The study of the relationship between 198 plasmatic fluvoxamine dosages and posology has been done on a sample of 80 inpatients. It shows that plasmatic levels increase proportionally with posology p.o. In contrast, plasmatic levels seem to be independent from weight and age of inpatients.

Topics: Aging; Body Weight; Depressive Disorder; Fluvoxamine; Hospitalization; Humans

Topics: Adult; Aged; Body Temperature; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Maprotiline; Middle Aged; Psychiatric Status Rating Scales; Thyroid Hormones

Platelet 5-HT levels and scores on the 17-item Hamilton Rating Scale for Depression (HRS) were studied in patients with unipolar depression before and after antidepressant treatment. Before treatment there were no differences in platelet 5-HT values or in HRS scores between patients who showed a good and a poor therapeutic response. Repeated administration of 5-HT uptake inhibitors (amitriptyline, clovoxamine, fluvoxamine) for 28 days markedly decreased platelet 5-HT levels. Chronic treatment with trazodone or maprotiline (weak inhibitors of platelet 5-HT uptake) produced no changes in platelet 5-HT levels. No significant correlation was observed between platelet 5-HT concentrations and the HRS scores before or during treatment. The findings suggest that the changes in platelet 5-HT levels after antidepressant treatment are mainly due to the effects of antidepressants on the 5-HT uptake system.

Topics: Adult; Aged; Amitriptyline; Antidepressive Agents; Blood Platelets; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Maprotiline; Middle Aged; Oximes; Psychiatric Status Rating Scales; Serotonin; Trazodone

Although there is a body of literature on the therapeutic efficacy of sleep deprivation (SD) there are only a few investigations in which the relevance of antidepressive medication for the clinical efficacy of SD has been studied. Based on the literature and on our own investigations with major depressed patients it seems that for the day-1 response it does not matter if and what type of antidepressive medication the patient receives. Furthermore, the results of our double blind study reveal that the day-1 response to total sleep deprivation (TSD) is not associated with a clear relationship to the outcome after 4 weeks treatment with either fluvoxamine or maprotiline. On the other hand, our data indicate that the day-2 response to TSD is significantly correlated with a beneficial outcome after subchronic treatment with maprotiline.

Topics: Antidepressive Agents; Combined Modality Therapy; Depressive Disorder; Double-Blind Method; Fluvoxamine; Humans; Maprotiline; Psychiatric Status Rating Scales; Sleep Deprivation

A multicenter controlled study was designed to test the hypothesis that a loading dose of an antidepressant could shorten the latency of its clinical efficacy. Three parallel groups of about 40 endogenous depressive inpatients received either a loading dose of milnacipran (300 mg daily for 2 weeks and 150 mg daily during the 2 following weeks), the standard regimen of milnacipran in severe depression (200 mg daily for 4 weeks), or fluvoxamine (200 mg daily for 4 weeks). The duration of the study was 4 weeks, with assessments at baseline and after 4, 9, 14, 21, and 28 days of therapy by means of Montgomery and Asberg depression scale (MADS), the Hamilton depression scale, the Clinical Global Impressions (CGI), and a checklist of symptoms and side-effects. Results showed very similar evolution in the 3 treatment groups. In addition, the level of side-effects did not exhibit significant differences among the treatment groups, except for excitement-nervousness and akathisia which were more frequently reported with fluvoxamine. These results do not support the usefulness of a loading dose of an antidepressant such as milnacipran. They demonstrate however that milnacipran can be given at a 300 mg daily dose from the very first day of treatment with an excellent tolerance.

Topics: Adult; Aged; Antidepressive Agents; Cyclopropanes; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Milnacipran; Psychiatric Status Rating Scales; Pulse

Electroencephalogram sleep measures over a 4-week period were obtained on 35 inpatients with major depression (unipolar) who received either fluvoxamine or desipramine in a randomized double-blind trial. Fluvoxamine showed immediate rapid eye movement (REM) sleep suppression and an alerting effect on sleep continuity measures. In contrast, desipramine administration was associated with REM suppression and sleep continuity improvement. The "alerting" quality of fluvoxamine, similar to other serotonergic antidepressants, appears to be unrelated to a lack of clinical efficacy, but may be related to persistent REM sleep suppression. However, it is premature to comment on the serotonin specificity for REM sleep.

Topics: Adult; Antidepressive Agents; Arousal; Delta Rhythm; Depressive Disorder; Desipramine; Double-Blind Method; Electroencephalography; Female; Fluvoxamine; Humans; Male; Middle Aged; Oximes; Signal Processing, Computer-Assisted; Sleep, REM

In a double blind study performed in psychiatric clinics the efficacy and tolerability of the new antidepressant Moclobemide was compared. Moclobemide belongs to a new class of substances called RIMA (Reversible Inhibitor of the monoamine oxidase type A). 61 patients with major depression (according to DSM-III) were either treated with Moclobemide or Fluvoxamine, a selective reuptake-inhibitor of 5-HT. The latter belongs to a class of antidepressants known for their better tolerability compared to tricyclic antidepressants. Moclobemide was as effective as Fluvoxamine but much better tolerated as shown by a lower incidence of side effects such as gastrointestinal problems or headache.

Topics: Adult; Aged; Antidepressive Agents; Benzamides; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Middle Aged; Moclobemide; Monoamine Oxidase Inhibitors; Oximes; Serotonin Antagonists

This is a multicentre double-blind study of fluvoxamine versus mianserin in the treatment of major depressive episode in patients over 65 years of age. Fifty-seven patients received either fluvoxamine (100-200 mg daily) or mianserin (40-80 mg daily). There was no statistically significant difference in improvement between the 2 treatment groups as measured by the Montgomery-Asberg Depression Rating Scale. Eleven patients (7 in the fluvoxamine group and 4 in the mianserin group) discontinued treatment because of intolerance. No statistically significant differences were seen in biological parameters with either drug. Both drugs improved the symptoms of depression though the overall response rate was not outstanding. The side effects profile for the fluvoxamine was contrary to previous studies in that frequent nausea and vomiting were not seen.

Topics: Aged; Aged, 80 and over; Antidepressive Agents; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Follow-Up Studies; Hospitalization; Humans; Male; Mianserin; Oximes; Psychiatric Status Rating Scales

H.M. van Praag has been suggesting a reappraisal of syndromes in psychiatry for over 20 years. He has tried to define syndromes originating from the same biochemical disorder. He has denoted this concept as 'functional psychopathology'. As an example of such a functional syndrome, he has cited the serotonin-shortage syndrome which unifies various psychiatric symptoms under a new point of view. The treatment of the serotonin-shortage syndrome is best served by psychopharmaca which raise the metabolism of serotonin in the synaptic cleft, e.g. the selective serotonin re-uptake inhibitors. Borrowing F. Freyhan's concept of 'target symptoms', one can now speak of 'functional target syndromes', within the frame of functional psychopathology.

Topics: 5-Hydroxytryptophan; Adult; Aged; Aged, 80 and over; Antidepressive Agents; Brain; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Oximes; Psychiatric Status Rating Scales; Receptors, Serotonin; Serotonin; Serotonin Antagonists

Fluvoxamine, a selective serotonin reuptake inhibitor, was compared with lorazepam in a multicentre double-blind, parallel group study in 112 general practice patients with mixed anxiety and depression. For inclusion, patients were required to have minimum baseline scores of 21 on the Montgomery-Asberg Depression Rating Scale (MADRS) and 11 on the Clinical Anxiety Scale (CAS). Treatment was for 6 weeks. There were no significant differences between treatments at any point except in an elderly subgroup in whom anxiety improved more rapidly with lorazepam. There were significant improvements in MADRS, CAS and global ratings compared with baseline at all subsequent assessments. Improvement continued during the whole treatment period. Lorazepam produced more sedation, whilst fluvoxamine produced significantly more nausea and vomiting; this was usually early in onset and, if tolerated, resolved during the course of the study. As it is now widely recognized that benzodiazepines should only be given in short courses of 2-4 weeks, the continued improvement up to 6 weeks has implications regarding choice of treatment.

Topics: Adult; Aged; Aged, 80 and over; Antidepressive Agents; Anxiety Disorders; Depressive Disorder; Double-Blind Method; Family Practice; Female; Fluvoxamine; Humans; Lorazepam; Male; Middle Aged; Multicenter Studies as Topic; Oximes; Personality Tests; United Kingdom

The authors employed a double-blind, placebo-controlled design to investigate the effectiveness of fluvoxamine versus imipramine in 54 outpatients with moderate major depression. Fluvoxamine proved superior to placebo but not to imipramine on the Hamilton Rating Scale for Depression and the Montgomery and Asberg Depression Rating Scale. Nausea and hyperarousal were the most common side effects in the fluvoxamine-treated patients.

Topics: Adolescent; Adult; Aged; Ambulatory Care; Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Fluvoxamine; Humans; Imipramine; Middle Aged; Oximes; Placebos

To evaluate whether serotonin reuptake inhibition is critical to the treatment of obsessive-compulsive disorder, 40 outpatients with a principal diagnosis of obsessive-compulsive disorder were randomized in a double-blind fashion to 8 weeks of treatment with either the serotonin reuptake inhibitor fluvoxamine maleate (n = 21) or the norepinephrine reuptake inhibitor desipramine hydrochloride (n = 19). Fluvoxamine was significantly better than desipramine in reducing the severity of obsessive-compulsive symptoms, as measured by the Yale-Brown Obsessive Compulsive Scale and by the global response rate ("responder" equaling "much improved"). Eleven of 21 patients were responders with fluvoxamine compared with 2 of 19 patients with desipramine. Fluvoxamine, but not desipramine, was also effective in reducing the severity of "secondary" depression. Fluvoxamine-induced improvement in symptoms of obsessive-compulsive disorder was not correlated with the severity of baseline depressive symptoms. This study provides additional evidence that the acute serotonin reuptake properties of a drug are predictive of its anti-obsessive-compulsive efficacy. It is hypothesized that the mechanism of action of serotonin reuptake inhibitors in obsessive-compulsive disorder may be related to chronic treatment-induced adaptive changes in presynaptic serotonin receptor function (eg, autoreceptor desensitization) and/or indirect influences on dopaminergic function (eg, in the basal ganglia).

Topics: Adult; Anxiety Disorders; Basal Ganglia; Depressive Disorder; Desipramine; Dopamine; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Obsessive-Compulsive Disorder; Oximes; Panic; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Receptors, Serotonin; Serotonin; Serotonin Antagonists

To test the hypothesis that the antidepressant effects of total sleep deprivation (TSD) are linked to the serotonergic and/or noradrenergic system the authors carried out a double-blind study (fluvoxamine versus maprotiline) in 42 inpatients with endogenous depression (ICD). Patients were randomized to a four-week treatment with either fluvoxamine (100-300 mg/day) or maprotiline (100-300 mg/day). In addition, patients underwent a TSD procedure before and after one week of antidepressant medication. There was a statistically significant reduction of depression ratings (HDRS) in both the fluvoxamine and maprotiline group. The day-1 response to TSD before antidepressive medication was not associated with a clear relationship to the outcome after four weeks of treatment with either fluvoxamine or maprotiline. On the other hand, the day-2 response to TSD was significantly correlated with a good outcome to subchronic treatment with maprotiline. Furthermore, the results of the authors' data suggest that a favorable short-term outcome of TSD may be connected to antidepressants enhancing the serotonergic neurotransmission. The global comparison between fluvoxamine and maprotiline revealed that the group of patients treated with fluvoxamine had a significantly higher efficiency index (CGI) than the maprotiline group; fluvoxamine was rated to be tolerated excellently in 70% of the patients whereas this percentage was only 43% in the maprotiline group. There was also significantly more vertigo and dry mouth in the maprotiline group whereas the fluvoxamine group was rated to have significantly more sleep disturbances during the trial.

Topics: Adult; Aged; Anthracenes; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Heart Rate; Humans; Male; Maprotiline; Middle Aged; Oximes; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Sleep Deprivation

Forty patients with a diagnosis of major depressive disorder were entered in a double-blind study to assess comparative clinical response and pharmacologic parameters of fluvoxamine, a highly selective blocker of serotonin reuptake, and desipramine, a noradrenergic agent. Eighteen patients receiving desipramine and 17 patients receiving fluvoxamine completed the study. Fluvoxamine was comparable to desipramine in its antidepressant efficacy and was better tolerated and caused minimal side effects. There was a direct linear relationship between plasma fluvoxamine levels and clinical response and a nonlinear relationship between plasma desipramine levels and clinical response. The pharmacologic specificity of the two drugs was assessed by determining uptake inhibition of serotonin and norepinephrine. The authors found a positive relationship between Hamilton Rating Scale for Depression scores and norepinephrine uptake inhibition for desipramine but found no such relationship between fluvoxamine and serotonin uptake inhibition. Although there was a clear-cut difference in the quality of pharmacologic specificity and a partial relationship to clinical response, the authors were unable to identify neuropharmacologic factors that would predict either treatment response or selective amelioration of symptomatologies in this patient population.

Topics: Adult; Antidepressive Agents; Depressive Disorder; Desipramine; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Norepinephrine; Oximes; Personality Inventory; Psychiatric Status Rating Scales; Serotonin; Serotonin Antagonists

Following an initial double-blind, randomized, parallel treatment group comparison of fluvoxamine, desipramine, and placebo in 89 outpatients with major depression at two centers, double-blind crossover to fluvoxamine was offered to 13 of 22 desipramine-treated completers of the initial phase who were considered failures on desipramine. Twelve elected to cross over to blinded fluvoxamine, and eleven continued on fluvoxamine for at least eight weeks. Nine of these eleven improved, and overall there was a statistically significant decrease in average Hamilton Depression Scores, from 24 to 13, for these fluvoxamine-treated desipramine-resistant patients.

Topics: Adult; Antidepressive Agents; Depressive Disorder; Desipramine; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Oximes; Psychiatric Status Rating Scales; Serotonin Antagonists

A double-blind, controlled study was carried out in 20 patients diagnosed as suffering from depressive disorder according to DSM-III criteria to compare the effectiveness and tolerability of fluvoxamine, a serotonin re-uptake inhibitor, with that of imipramine. Patients were allocated at random to receive one or other drug for a period of 4 weeks, dosage starting at 50 mg for the first 3 days and increasing to 100 mg daily for a further 3 days. Dosage was continued at this level for the remainder of the trial but was increased, if necessary, to 150 mg daily in two divided doses. Assessments of symptom severity were made on entry and response after 1, 2 and 4 weeks of treatment using the Hamilton Rating Scale for Depression, the Clinical Global Impression and a Visual Analogue Scale. Tolerability was assessed using the Dosage Record and Treatment Emergent Symptom Scale. The results showed that at the end of the trial there was a significant reduction in depressive symptoms severity in both groups and that fluvoxamine was significantly more effective than imipramine in reducing suicidal ideas and anxiety/somatic symptoms. Both drugs were relatively well tolerated but the side-effect profiles were different, being mainly of the anticholinergic type with the tricyclic and gastro-intestinal with fluvoxamine.

Topics: Adult; Aged; Antidepressive Agents; Depressive Disorder; Double-Blind Method; Drug Administration Schedule; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Oximes

1. The efficacy of fluvoxamine is compared to that of desipramine in a multicenter double blind placebo controlled six-week flexible dose trial of 90 outpatients with major depressive disorder. 2. Although overall drug effects were relatively weak, there were trends suggesting separation of both active drugs from placebo at week six. Both drugs were well tolerated. 3. Studies of major depression ought to be designed to last 8-10 weeks in order to demonstrate placebo active drug differences and the stability of such a difference should it occur in the first six weeks.

Topics: Adult; Antidepressive Agents; Depressive Disorder; Desipramine; Double-Blind Method; Fluvoxamine; Humans; Outpatients; Oximes; Placebos; Psychiatric Status Rating Scales; Random Allocation

The efficacy and CNS effects of the selective 5-HT re-uptake inhibitor fluvoxamine were compared with mianserin in depressed hospital out-patients in a double-blind randomized trial. Patients had to meet DSM-III criteria for Major Depressive Episode and achieve a score of at least 30 on the Montgomery-Asberg Depression Rating Scale (MADRS) after a 1-week placebo baseline period. Active treatment was for 6 weeks with an initial dose of either 100 mg fluvoxamine or 60 mg mianserin; after 1 week the dosage could be increased to 300 mg or 180 mg, respectively. Data from 63 patients (30 received fluvoxamine) were analyzed. The treatment groups were comparable with regard to age and history and severity of depression. Efficacy assessments showed similar improvements with each drug; MADRS scores improved by 65.6% with fluvoxamine and by 60.8% with mianserin. There were no significant differences between treatments at any assessment. Sedative effects were assessed using the Leeds Sleep Evaluation Questionnaire and the Digit Symbol Substitution Test. Mianserin caused a shift towards sedation in the first week in all visual analogue scales; getting to sleep and sleep quality were improved but waking was more difficult than with fluvoxamine. Similarly, the mianserin group performed less well on the Digit Symbol Substitution Test. The study confirmed that both drugs are effective treatments for depressive illness but that mianserin gives rise to sedation during the first week.

Topics: Adult; Antidepressive Agents; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Mianserin; Oximes; Prospective Studies; Sleep

It has been hypothesized that enhancement of brain serotoninergic (5-HT) function is involved in the mechanism of action of some antidepressants. To test this, the prolactin response to intravenously administered tryptophan, a clinical measurement of 5-HT function, was assessed before and during antidepressant treatment. Depressed patients received the tricyclic desipramine hydrochloride (N = 24) or the 5-HT reuptake inhibitor fluvoxamine maleate (N = 30). The prolactin response was significantly enhanced after long-term treatment (4 weeks) but not as reliably increased after short-term (1-week) desipramine treatment. Fluvoxamine enhanced the prolactin response after both short- and long-term treatment. Enhancement of the prolactin response was not clearly correlated with clinical improvement. The results of this study are consistent with preclinical evidence of enhanced 5-HT function during treatment with these classes of antidepressants, but also indicate that enhanced 5-HT function is not a sufficient condition for antidepressant efficacy.

Topics: Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Desipramine; Double-Blind Method; Fluvoxamine; Humans; Oximes; Prolactin; Serotonin; Serotonin Antagonists; Time Factors; Tryptophan

Seventy-two depressed patients attending general practices were randomly allocated to treatment with either flupenthixol dihydrochloride (1 to 2 mg/day) or fluvoxamine maleate (100 to 200 mg/day) to assess efficacy and side-effects over a 4-week period. Clinical assessments were carried out before medication (Day 1) and on Days 8, 15 and 29 of treatment using the Hamilton Rating Scale for Depression, Clinical Global Impressions (CGI) and a patient self-assessment visual analogue scale for depression. Unwanted symptoms were also recorded. Reduction in mean total scores on the Hamilton scale at each assessment and therapeutic effect improvement on the CGI were greater for patients treated with flupenthixol (p less than 0.05). Reduction in unwanted symptoms was progressive in both groups, but more pronounced in patients receiving flupenthixol. Twice as many new symptoms arose in the fluvoxamine group compared to the flupenthixol group. Four patients were withdrawn in the fluvoxamine group due to untoward drug effects compared with none in the flupenthixol group.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Depressive Disorder; Female; Flupenthixol; Fluvoxamine; Humans; Male; Middle Aged; Oximes; Psychiatric Status Rating Scales; Thioxanthenes

Topics: Adult; Aged; Aged, 80 and over; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Outpatients; Oximes; Random Allocation

A double-blind comparative study with fluvoxamine, a specific serotonin uptake inhibitor, and maprotiline, a specific noradrenaline uptake inhibitor, was conducted in 44 patients suffering from panic disorder with or without phobic avoidance. Patients were treated with 150 mg of either fluvoxamine or maprotiline daily for 6 weeks. Fluvoxamine was found to be a potent anti-panic agent. The number of panic attacks decreased significantly during treatment. The level of anxiety showed a noteworthy time course. After an initial increase during the first week of treatment, the level of anxiety declined significantly as compared to baseline on continuation of the treatment. The therapeutic properties of fluvoxamine were therefore apparent from week 4 on. In addition, the associated depressive symptomatology decreased as well. Relative to fluvoxamine, maprotiline was ineffective in the treatment of panic disorders. Maprotiline had a slight effect on the depressive symptoms but virtually no effect on the level of anxiety. These findings support the hypothesis that serotonergic pathways in the brain are implicated in the pathogenesis of panic disorders. The data are at variance, however, with findings indicating that drugs that are efficacious in panic disorder act by altering noradrenergic function.

Topics: Adult; Agoraphobia; Anthracenes; Anxiety Disorders; Brain; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Fear; Female; Fluvoxamine; Humans; Male; Maprotiline; Oximes; Panic; Phobic Disorders; Psychological Tests; Receptors, Adrenergic; Receptors, Serotonin; Serotonin Antagonists

Topics: Adult; Aged; Antidepressive Agents; Depressive Disorder; Dibenzothiepins; Dothiepin; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Oximes; Prospective Studies; Random Allocation

Antidepressants are ineffective in about 30% of patients with major depression. Some authors then advise treatment of non-responders with (non-tricyclic) more selective reuptake inhibitors. In a double-blind, partial crossover study, 71 patients were selected for treatment during 4 weeks with oxaprotiline and/or fluvoxamine, two non-tricyclic antidepressants that are selective reuptake inhibitors or noradrenaline and serotonin respectively. All patients had failed to respond to earlier treatment with cyclic antidepressants during the current episode. Only 13% of the patients responded, with 27% of them responding to oxaprotiline and none to fluvoxamine. Moreover, a low response of 27% was also obtained in the crossover phase, which included all non-responders to the first treatment, oxaprotiline being effective in 39% and fluvoxamine in 10% of the patients. The results indicate that selective reuptake inhibitors are not an effective alternative for non-responders to other cyclic antidepressants and that non-responders to "noradrenergic" antidepressants do not appear to have much chance of responding to "serotonergic" antidepressants and vice versa.

Topics: Adult; Anthracenes; Bipolar Disorder; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Maprotiline; Middle Aged; Oximes; Personality Disorders; Psychological Tests; Psychometrics

Antidepressants are ineffective in about 30% of the patients with major depression. Besides electroconvulsive therapy (ECT) and lithium, MAO inhibitors have been suggested as an alternative in such patients. In 2 controlled, partial crossover studies involving 47 patients with major depression who had already been treated unsuccessfully with at least 2 cyclic antidepressants, the effect of the MAO inhibitor tranylcypromine was studied. The first study was an open comparison with L-5-hydroxytryptophan (L-5HTP), the second study a double-blind comparison with nomifensine. Neither the patients treated with L-5HTP nor the patients treated with nomifensine, except one, improved. In contrast, tranylcypromine was effective in 50% of the patients. The depressions of the responders to tranylcypromine appeared to be more endogenous (according Newcastle Scale II) and of shorter duration than those of the non-responders. It is concluded that MAO inhibitors such as tranylcypromine are an effective alternative to ECT and lithium in patients with major depression who have failed to respond to cyclic antidepressants.

Topics: 5-Hydroxytryptophan; Adult; Aged; Clinical Trials as Topic; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Resistance; Female; Fluvoxamine; Humans; Male; Maprotiline; Middle Aged; Nomifensine; Oximes; Psychological Tests; Tranylcypromine

The development of a new class of antidepressants that have in common their ability to inhibit the reuptake of serotonin at neuronal synapses is reviewed. There is accumulating evidence that this class of medications constitutes an advance in the management of depression; these drugs appear to be effective antidepressants with a possibly lower and more acceptable incidence of adverse reactions than the tricyclic compounds. Further exploration of these potential advantages and of the usefulness of this group of compounds for other clinical syndromes is justified.

Topics: Citalopram; Clinical Trials as Topic; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Oximes; Propylamines; Serotonin Antagonists; Zimeldine

A placebo-controlled, double-blind study of 63 inpatients with major affective disorder was performed to compare the safety and efficacy of fluvoxamine and imipramine. Results indicate that fluvoxamine and imipramine are superior to placebo and demonstrate a trend toward superiority of fluvoxamine over imipramine. Fluvoxamine was generally well tolerated in most patients.

Topics: Adult; Aged; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Oximes; Personality Inventory; Placebos; Psychiatric Status Rating Scales; Random Allocation

The antidepressive properties of the specific serotonin reuptake inhibitor fluvoxamine and the specific norepinephrine reuptake inhibitor oxaprotiline were investigated in a sequential design with the aim of evaluating the hypothesis that two distinct biochemical subtypes of depression exist. Responders were treated for 7 weeks with the compound to which they had responded. After 1 placebo week, the nonresponders were switched to the alternative compound. An evaluation of the data obtained during the 3-week treatment periods from 24 patients (37 trials) with major depression revealed a highly significant reduction of Hamilton Scores with both compounds, oxaprotiline and fluvoxamine. If the patients with major depression are subdivided into two groups, endogenous depressives and neurotic depressives, there is no significant difference between the therapeutic improvements (both compounds) achieved in the two groups. The data shows that only about 20% of the nonresponders on one compound responded to the alternative drug, whereas 90% of responders (within 3 weeks) were still responders after 7 weeks. The data are at variance with the concept of two distinct biochemical subtypes of depression (serotonergic vs. norepinephrinergic). Dexamethasone suppression tests, performed in 23 patients, gave no prognostic hint as to whether the patients reacted well to drug therapy or not.

Topics: Adult; Aged; Anthracenes; Antidepressive Agents; Depressive Disorder; Dexamethasone; Female; Fluvoxamine; Humans; Hydrocortisone; Male; Maprotiline; Middle Aged; Norepinephrine; Oximes; Prognosis; Psychiatric Status Rating Scales; Serotonin

Following a multicentre double-blind controlled trial comparing the effects of fluvoxamine and imipramine in depressed inpatients (M.D.E.) 39 patients continued on longer term treatment with maintenance of double-blind conditions (17 on fluvoxamine, 22 on imipramine). The results regarding the reasons for premature interruption of treatment show a slight advantage in favour of fluvoxamine. There were several significant differences in favour of fluvoxamine at the 20th week. The most common side-effects were hot flushes with imipramine and dizziness with fluvoxamine. Overall, despite the small number of patients, the results show a greater clinical tolerance to fluvoxamine than to imipramine.

Topics: Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Imipramine; Long-Term Care; Male; Middle Aged; Oximes; Psychiatric Status Rating Scales

Sixteen outpatients who met DSM-III criteria for obsessive-compulsive disorder completed a 20-week double-blind, crossover trial with fluvoxamine and placebo. Thirteen (81%) improved with fluvoxamine, while three (19%) improved with placebo. Fluvoxamine treatment was associated with significant improvement on measures of obsessive-compulsive symptoms, anxiety, and depression. Depressed subjects' improvement on obsessive-compulsive measures correlated with improvement in symptoms of depression. Nondepressed subjects also showed improvement on measures of obsessive-compulsive symptoms. In this trial, fluvoxamine was an effective and safe treatment for obsessive-compulsive disorder.

Topics: Adolescent; Adult; Ambulatory Care; Anxiety Disorders; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Obsessive-Compulsive Disorder; Oximes; Personality Inventory; Placebos; Psychiatric Status Rating Scales

Of nine nonsuppressors on the dexamethasone suppression test (DST), five (56%) developed intolerable side effects during treatment with fluvoxamine, a new serotonin uptake inhibiting antidepressant, compared with three of 24 suppressors (13%).

Topics: Adult; Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Dexamethasone; Double-Blind Method; Female; Fluvoxamine; Humans; Hydrocortisone; Male; Nausea; Oximes; Serotonin Antagonists; Vomiting

Topics: Adolescent; Adult; Aged; Child; Clinical Trials as Topic; Depressive Disorder; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Multi-Institutional Systems; Oximes; Research Design

Fluvoxamine was given in placebo-controlled trials to 33 severely depressed patients of between 60 and 71 years, 29 received imipramine and 14 placebo. At week 4 of treatment fluvoxamine and imipramine were superior to placebo on the HAMD and CGI scales (P less than 0.05). There was indication of an earlier onset of antidepressant activity in the fluvoxamine group. There was no evidence of systematic changes in laboratory variables in any treatment group. Fluvoxamine and placebo had similar effects on heart rate and blood pressure. Imipramine was associated with significant postural falls in mean systolic pressure. The most frequent unwanted symptom with fluvoxamine was mild nausea, with imipramine, dry mouth. Toxic confusion was the major reason for dropout in the imipramine (n = 4) and nausea (n = 3) in the fluvoxamine-treated group.

Topics: Aged; Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Oximes; Time Factors

Outpatients with major affective disorder, unipolar depressed type (N=101), were treated in a 4-week placebo-controlled double-blind study to compare the efficacy and safety of fluvoxamine, a new serotonin reuptake inhibitor antidepressant, with imipramine and placebo. Therapy was initiated at 50 mg/day; thereafter, dosage ranged between 100 and 300 mg/day for both drugs. Results indicate statistically significant efficacy, measured by both patient and physician rating scales, for both active drugs over placebo. Fluvoxamine showed some evidence of earlier onset of action. Anticholinergic side effects were more common in the imipramine-treated patients, while fluvoxamine produced more gastrointestinal distress and insomnia.

Topics: Adult; Aged; Ambulatory Care; Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Nausea; Oximes; Patient Dropouts; Placebos; Psychiatric Status Rating Scales; Sleep Initiation and Maintenance Disorders; Vomiting; Xerostomia

L-5HTP and tranylcypromine were compared in an open, but controlled and cross-over study, in patients suffering from major depression; all were non-responders to several reuptake inhibitors, including oxaprotiline and fluvoxamine. After four unsuccessful sleep-deprivations, L-5HTP or tranylcypromine were given during four weeks in a crossover design. Of 17 patients given L-5HTP during both treatment periods, none responded, whereas of 26 patients treated with tranylcypromine, 15 responded. Thus, L-5HTP is not a therapeutically effective alternative in depressed patients who have not responded to reuptake inhibitors.

Topics: 5-Hydroxytryptophan; Adult; Aged; Carbidopa; Clinical Trials as Topic; Depressive Disorder; Drug Resistance; Drug Therapy, Combination; Fluvoxamine; Follow-Up Studies; Humans; Maprotiline; Middle Aged; Oximes; Random Allocation; Serotonin Antagonists; Stereoisomerism; Tranylcypromine

In a placebo-controlled, double-blind study of 91 out-patient depressives, the anti-depressant effect of fluvoxamine, a selective serotonin uptake inhibitor was compared to that of imipramine. Overall drug effects were relatively weak but analyses in selected sub-groups showed both active drugs superior to placebo. Effects of fluvoxamine were more marked in non-situational depressives and it did not improve sleep while effects of imipramine were more marked in retarded depressives and on retardation ratings, suggesting that fluvoxamine may have a different pattern of clinical effects. Side effects of Fluvoxamine were predominantly gastrointestinal and it did not produce postural hypotension or anticholinergic side-effects.

Topics: Adult; Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Imipramine; Male; Oximes; Psychological Tests

Topics: Adolescent; Adult; Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Oximes; Random Allocation

1 The effects of fluvoxamine to a maximum of 300 mg daily were compared with those of imipramine to a maximum of 200 mg daily, in 151 patients with primary major depression. 2 Four weeks of treatment with fluvoxamine resulted in 67.2% improvement (+/- s.d. 21.6) on the Hamilton Rating Scale for Depression (26 items). Treatment with imipramine showed 62.1% improvement (+/- s.d. 29.5) on this scale. 3 Fluvoxamine had no untoward effects on the cardiovascular system, while imipramine produced systematic increases in the postural fall in blood pressure. Dry mouth, nausea, daytime somnolence and tremor were seen with fluvoxamine treatment, while imipramine was associated with dry mouth, daytime somnolence, dizziness and tremor. 4 We conclude that fluvoxamine seems to have the same general antidepressant efficacy as imipramine. It was not associated with any safety problems and was generally well tolerated.

Topics: Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Electroencephalography; Female; Fluvoxamine; Hemodynamics; Humans; Imipramine; Male; Oximes; Psychiatric Status Rating Scales

1 We report the results of a comparative clinical trial of a new antidepressant drug fluvoxamine (a specific re-uptake inhibitor of 5-hydroxytryptamine (5-HT)) with chlorimipramine. Thirty-two patients with mixed depression received one or the other drug at the same daily dosage of 150 mg. 2 In both drug groups there was an overall clinically significant improvement for all items on the Hamilton Rating Scale for Depression (67% improvement in both groups). 3 In the chlorimipramine group there were more digestive symptoms and anticholinergic effects; the difference with the fluvoxamine group approached statistical significance. 4 No clinically important effects of either treatment were observed on heart-rate or blood pressure.

Topics: Adult; Antidepressive Agents; Clinical Trials as Topic; Clomipramine; Depressive Disorder; Double-Blind Method; Electroencephalography; Female; Fluvoxamine; Humans; Male; Middle Aged; Oximes; Psychiatric Status Rating Scales

1 Two double-blind, randomised studies were performed to compare the efficacy of fluvoxamine and chlorimipramine in depressed patients. In the first study the effects of a single daily dosage of between 100 and 300 mg of fluvoxamine were compared with those of chlorimipramine at a dosage of 50-150 mg daily in 43 out-patients with endogenous depression. 2 In a second study using three times daily dosing with a daily dosage of 150-300 mg for both fluvoxamine and chlorimipramine, 30 in-patients with unipolar depression were assessed. 3 Four weeks of treatment with single daily dosing resulted in a mean improvement of 61.4% (+/- s.d. 31.7) on the Hamilton Rating Scale for Depression (HAMD) for fluvoxamine and of 65.3% (+/- s.d. 25.8) for chlorimipramine. In the study with three times daily dosing the mean results were 72.9% (+/- s.d. 22.3) improvement for fluvoxamine and 62.1% (+/- s.d. 28.5) for chlorimipramine. 4 At similar dosages, fluvoxamine had significantly less untoward effects on blood pressure than chlorimipramine. Anticholinergic effects were also fewer in the fluvoxamine group, as were nervous system symptoms, with the latter difference reaching statistical significance (P = 0.02). 5 We conclude that fluvoxamine, given in a single daily dose of 150-250 mg, provides antidepressant efficacy similar to chlorimipramine. At this dosage it may be expected to produce less anticholinergic effects and have less influence on blood pressure than chlorimipramine.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Bipolar Disorder; Clinical Trials as Topic; Clomipramine; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Hemodynamics; Humans; Male; Middle Aged; Oximes

1 A double-blind placebo-controlled study of fluvoxamine and imipramine was performed in a group of depressed patients. Twenty-two patients received fluvoxamine (mean dose 101 mg/day), 25 received imipramine (mean dose 127 mg/day) and 22 received placebo. 2 Apart from an increase in the SGOT and SGPT values of four imipramine patients, no statistically significant changes in haematology or urinalysis were judged to be medically relevant. Fluvoxamine exhibited fewer anticholinergic side effects than imipramine. 3 Both fluvoxamine treated patients and imipramine-treated patients exhibited a statistically significant improvement at the end of the 28-day treatment period with respect to the placebo patients, as measured using the Hamilton Rating Scale for Depression, and the Clinical Global Impression Scale. Evaluations of the results of the Beck Depression Inventory and the Profile of Mood States revealed a statistically significant improvement for imipramine patients with respect to placebo at week 4, but not for fluvoxamine patients. It is postulated on the basis of quantitative pharmaco-EEG findings, that the slight superiority of imipramine over fluvoxamine was due to underdosing of the latter.

Topics: Adult; Aged; Antidepressive Agents; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Electroencephalography; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Oximes; Psychiatric Status Rating Scales

Thirty patients were treated in a randomised double-blind efficacy study of fluvoxamine and chlorimipramine. The dose range for both drugs was 50-300 mg in divided daily doses. Mean daily doses were higher for fluvoxamine than chlorimipramine. Generally the baseline recordings were comparable for both drug groups. Fluvoxamine was superior to chlorimipramine in all the rating scales used without achieving statistical significance. Chlorimipramine, but not fluvoxamine, caused a significant decrease in blood pressure. There were no significant effects on ECG or laboratory variables. There was no significant relationship between plasma levels of either compound or metabolite and clinical response. Chlorimipramine exerted more unwanted effects than fluvoxamine. Autonomic effects of fluvoxamine were minimal in comparison with chlorimipramine. Chlorimipramine patients required more concurrent anxiolytic medication than fluvoxamine. Both drug groups required a significant amount of concurrent hypnotic medication.

Topics: Adolescent; Adult; Antidepressive Agents; Bipolar Disorder; Clomipramine; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Oximes; Psychiatric Status Rating Scales; Random Allocation

1. Fluvoxamine is a potent serotonin re-uptake inhibitor, with little or no noradrenergic or anticholinergic activity. 2. The results of three studies using an almost identical protocol with a prospectively randomized, double-blind design comparing fluvoxamine and chlorimipramine are presented. 3. In a population of 98 subjects suffering from a variety of depressive conditions, there was a marked improvement over four weeks in both groups. dosage was maintained between 150 and 300 mg per day. 4. There were no changes of clinical importance in vital signs, hematology or biochemistry, but pulse rates increased in the chlorimipramine group. 5. There were fewer concurrent signs and symptoms in the fluvoxamine group, especially those attributable to anticholinergic activity.

Topics: Antidepressive Agents; Bipolar Disorder; Clinical Trials as Topic; Clomipramine; Depressive Disorder; Double-Blind Method; Fluvoxamine; Humans; Oximes; Receptors, Serotonin

Topics: COVID-19 Drug Treatment; Depressive Disorder; Fluvoxamine; Humans; Outpatients

Topics: Animals; COVID-19 Drug Treatment; Depressive Disorder; Drug Repositioning; Fluvoxamine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Neurotransmitter Agents; Psychopharmacology

The purpose of the study was to investigate what effects the sigma-1 receptor (S1R) could exert on the cardiac myocyte ion channels in a rodent model of depression and to explore the underlying mechanisms since depression is an independent risk factor for cardiovascular diseases including ventricular arrhythmias (VAs).. To establish the depression model in rats, chronic mild unpredictable stress (CMUS) for 28 days was used. The S1R agonist fluvoxamine was injected intraperitoneally from the second week to the last week for 21 days in total, and the effects were evaluated by patch clamp, western blot analysis, and Masson staining.. Activation of S1R could decrease the vulnerability to VAs by inhibiting I

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Depression; Depressive Disorder; Disease Models, Animal; Fluvoxamine; Heart Ventricles; Ion Channels; Male; Myocytes, Cardiac; Rats; Rats, Sprague-Dawley; Receptors, sigma; Sigma-1 Receptor; Ventricular Remodeling

Pregnancy may cause changes in drug disposition. The clinical consequences may be profound and even counterintuitive; in some cases pregnant women may need more than twice their usual drug dose in order to maintain therapeutic drug levels. For antidepressants, evidence on drug disposition in pregnancy is scarce. The aim of this study was to determine the effects of pregnancy on serum levels of selective serotonin reuptake inhibitors (SSRIs) and venlafaxine in a large and naturalistic patient material, in order to provide tentative dose recommendations for pregnant women.. Using patient data from two routine therapeutic drug monitoring (TDM) services in Norway with linkage to the national birth registry, dose-adjusted serum drug concentrations of SSRIs and venlafaxine during pregnancy were compared to the women's own baseline (non-pregnant) values, using a linear mixed model.. Overall, the TDM databases contained 196,726 serum concentration measurements from 54,393 women. After data linkage and drug selection (SSRIs or venlafaxine only), we identified 367 analyses obtained from a total of 290 pregnancies in 281 women, and 420 baseline observations from the same women. Serum concentrations in the third trimester were significantly lower than baseline for paroxetine (-51%; 95% confidence interval [CI], -66%, -30%; p<0.001), fluvoxamine (-56%; CI, -75%, -23%; p = 0.004) and citalopram (-24%; CI, -38%, -7%; p = 0,007), and higher than baseline for sertraline (+68%; CI, +37%, +106%; p<0.001). For escitalopram, fluoxetine and venlafaxine concentrations did not change significantly.. For paroxetine and fluvoxamine the pronounced decline in maternal drug serum concentrations in pregnancy may necessitate a dose increase of about 100% during the third trimester in order to maintain stable concentrations. For fluoxetine, venlafaxine, citalopram, escitalopram and sertraline, the present study indicates that dose adjustments are generally not necessary during pregnancy.

Topics: Adult; Antidepressive Agents; Citalopram; Databases, Factual; Depressive Disorder; Drug Monitoring; Female; Fluvoxamine; Humans; Norway; Paroxetine; Pregnancy; Pregnancy Trimester, Third; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride

Depression is highly prevalent in diabetes (DM). Brain-derived neurotrophic factor (BDNF) which is mainly regulated by the endoplasmic reticulum chaperon sigma-1 receptor (S1R) plays a relevant role in the development of depression.. We studied the dose-dependent efficacy of S1R agonist fluvoxamine (FLU) in the prevention of DM-induced depression and investigated the significance of the S1R-BDNF pathway.. We used streptozotocin to induce DM in adult male rats that were treated for 2 weeks p.o. with either different doses of FLU (2 or 20 mg/bwkg) or FLU + S1R antagonist NE100 (1 mg/bwkg) or vehicle. Healthy controls were also enrolled. Metabolic, behaviour, and neuroendocrine changes were determined, and S1R and BDNF levels were measured in the different brain regions.. In DM rats, immobility time was increased, adrenal glands were enlarged, and thymuses were involuted. FLU in 20 mg/bwkg, but not in 2 mg/bwkg dosage, ameliorated depression-like behaviour. S1R and BDNF protein levels were decreased in DM, while FLU induced SIR-BDNF production. NE100 suspended all effects of FLU.. We suggest that disturbed S1R-BDNF signaling in the brain plays a relevant role in DM-induced depression. The activation of this cascade serves as an additional target in the prevention of DM-associated depression.

Topics: Animals; Anisoles; Brain; Brain-Derived Neurotrophic Factor; Depression; Depressive Disorder; Diabetes Mellitus, Experimental; Fluvoxamine; Male; Narcotic Antagonists; Propylamines; Rats; Receptors, sigma; Selective Serotonin Reuptake Inhibitors; Sigma-1 Receptor; Signal Transduction

Psychiatric comorbidities are an important issue in the treatment of chronic dizziness patients.. To test the correlation between psychiatric status and subjective handicaps and to examine the effects of milnacipran on handicaps.. Hospital anxiety and depression scale (HADS) and handicaps were assessed by a questionnaire before and eight weeks after milnacipran treatment (50 mg/day) in 29 consecutive patients with chronic dizziness. Effects of milnaciplan were compared with fluvoxamine (200 mg/day).. A significant correlation was found between anxious and depressive scale scores and also between HADS and handicaps. Duration of symptoms was longer in the anxious/depressive group (HADS≧13) than in the non-anxious/depressive group. Handicaps and HADS were significantly decreased after treatment only in the anxious/depressive group. There were no overall differences in drug effects between milnaciplan and fluvoxamine. However, the rate of patients with a post/pre ratio of handicaps <80% was higher in milnaciplan group compared with the fluvoxamine group.. Not only anxiety disorders but also depression should be considered as comorbid psychiatric disorders in patients with chronic dizziness. Dizzy patients with psychiatric comorbidities have a longer duration of symptoms and more handicaps than those without psychiatric disorders. Milnacipran may be chosen as a treatment for patients with chronic dizziness with comorbid psychiatric disorders in case of and insufficient response to SSRIs.

Topics: Anxiety Disorders; Chronic Disease; Comorbidity; Cyclopropanes; Depressive Disorder; Dizziness; Female; Fluvoxamine; Humans; Male; Mental Disorders; Middle Aged; Milnacipran; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors

Reduced motivation is an important marker of psychiatric disorders, including depression. We describe the female encounter test, a novel method of evaluating reward-seeking behavior in mice.. The test apparatus consists of three open chambers, formed with partitions that allow the animal to move freely from one chamber to another. A test male mouse is habituated in the apparatus, and subsequently a female and male mouse are introduced into a wire-mesh box in the left and right chamber, respectively. The time the test male mouse spends in the female or male area is measured for 10 min.. All six strains of mice tested showed a significant preference for female encounters. The preference was observed in 7-30-week-old mice. The preference was blocked by castration of the resident male test mouse, and was not affected by the phase of the menstrual cycle of the female intruder. The preference was impaired in mouse models of depression, including social isolation-reared, corticosterone-treated, and lipopolysaccharide-treated mice. The impairment was alleviated by fluvoxamine in isolation-reared and lipopolysaccharide-treated mice, and it was improved by the metabotropic glutamate 2/3 receptor antagonist LY341495 in corticosterone-treated mice. Encounter with a female, but not male, mouse increased c-Fos expression in the nucleus accumbens shell of test male mice. Furthermore, both the preference and encounter-induced increases in c-Fos expression were blocked by dopamine D1 and D2 receptor antagonists.. These findings indicate that motivation in adult male mice can be easily evaluated by quantitating female encounters.

Topics: Amino Acids; Animals; Antidepressive Agents, Second-Generation; Castration; Choice Behavior; Corticosterone; Depressive Disorder; Disease Models, Animal; Equipment Design; Estrous Cycle; Excitatory Amino Acid Antagonists; Female; Fluvoxamine; Lipopolysaccharides; Male; Mice; Motivation; Nucleus Accumbens; Psychological Tests; Reward; Social Behavior; Social Isolation; Xanthenes

A 60-year-old woman reported horizontal "shimmering" movement while reading crossword puzzles when using fluvoxamine, bupropion, quetiapine, lithium, and levothyroxine. This visual disturbance, likely oscillopsia, started after the fluvoxamine was added and waned as the fluvoxamine was tapered, disappearing after the drug was discontinued. Genetic testing to explore how the patient metabolizes these medications combined with YouScript® interaction analysis suggest that she may have had abnormally high plasma concentrations of fluvoxamine during this time. Oscillopsia may be a novel dose-dependent side effect of fluvoxamine. Genetic testing combined with YouScript has the potential to discover novel drug side effects, elucidate drug interactions and guide future prescribing decisions.

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Bupropion; Depressive Disorder; Dopamine Uptake Inhibitors; Drug Interactions; Female; Fluvoxamine; Humans; Middle Aged; Ocular Motility Disorders; Precision Medicine; Quetiapine Fumarate

A comparative evaluation of the efficacy and safety of monotherapy with one of the modern antidepressants (venlafaxine, agomelatine, or fluvoxamine) and combination treatment of one of the above mentioned antidepressants with acetyl-L-carnitine (ALС, carnicetine) in the geriatric psychiatric unit.. Two groups of elderly patients (aged 60-79 years) with mild or moderate depression, randomized according to a number of demographic and clinical characteristics, were treated with antidepressants in monotherapy or combined therapy (antidepressant/carnicetine) within 8 weeks.. Combination therapy with the neurotrophic agent carnicetine proved to be more effective compared to monotherapy. At the end of treatment, the more rapid clinical response has been shown for depression, anxiety, apathy, and cognitive dysfunction. Furthermore, combination therapy provides less adverse effects.. Antidepressant/carnicetine combination therapy may be recommended for treatment of depression in elderly patients.. Цель исследования - сравнительная оценка эффективности и безопасности монотерапии одним из антидепрессантов последних поколений (венлафаксин, агомелатин или флувоксамин) и комплексной антидепрессивной терапии с применением одного из перечисленных антидепрессантов в сочетании с ацетил-L-карнитином (АЛК, карницетин) для лечения депрессий у больных пожилого возраста в условиях геронтопсихиатрического стационара. Материалы и методы. Две группы пожилых больных (от 60 до 79 лет) с легкой и умеренной депрессией, сопоставимые по основным демографическим, клиническим характеристикам, в течение 8 нед получали антидепрессивную моно- или комплексную (антидепрессант и АЛК) терапию. Результаты. Установлено, что применение комплексной терапии с включением нейропротектора с нейротрофическим и энерготропным механизмом действия карницетина позволяет добиться более быстрого терапевтического ответа и более выраженного эффекта по сравнению с монотерапией антидепрессантом, что подтверждается значимой редукцией депрессивных расстройств, в том числе показателей выраженности тревоги, а также улучшением когнитивного функционирования больных. Применение комплексной терапии сопровождалось уменьшением частоты нежелательных эффектов. Заключение. Полученные результаты позволяют рекомендовать включение карницетина в комплексную антидепрессивную терапию для применения в геронтопсихиатрическом стационаре.

Topics: Acetamides; Acetylcarnitine; Aged; Antidepressive Agents; Apathy; Cyclohexanols; Depressive Disorder; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Male; Middle Aged; Treatment Outcome; Venlafaxine Hydrochloride

Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine.. Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg) for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated.. The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased.. Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent.

Topics: Animals; Antidepressive Agents; Brain; Citric Acid Cycle; Creatine Kinase; Depressive Disorder; Electron Transport; Energy Metabolism; Fluvoxamine; Malate Dehydrogenase; Male; Rats, Wistar; Selective Serotonin Reuptake Inhibitors

Topics: Anxiety Disorders; Cataract; Depressive Disorder; Female; Fluvoxamine; Humans; Lens Implantation, Intraocular; Lens, Crystalline; Phacoemulsification; Selective Serotonin Reuptake Inhibitors; Vision Disorders; Visual Acuity; Young Adult

Olfactory bulbectomy (OBX) in rodents represents a valuable experimental model of depression. This study was designed to shed further light on the impact of putative serotonergic neuronal degeneration in OBX mice and to assess the effect of a widely used antidepressant on serotonergic related behavioral changes induced by OBX.. Adult male ddY mice were subject to bilateral OBX or sham surgery. The serotonin (5-HT)(2A/2C) receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) enhanced a head-twitch response (HTR) in OBX mice. Effects of 5-HT(2A), 5-HT(2C) antagonists and fluvoxamine were observed in OBX mice following DOI administration.. The HTR elicited by the administration of DOI (0.5 mg/kg and 1 mg/kg, i.p.) was increased about twofold in OBX mice when compared with controls on the 14th day after the surgery. The injection of ketanserin (0.025 mg/kg, i.p.), a 5-HT(2A) receptor antagonist, inhibited the enhancement of the DOI-induced HTR after OBX. Likewise, the administration of SB 242084 (1 mg/kg, s.c.), a 5-HT(2C) receptor antagonist, also inhibited the DOI-induced HTR in OBX mice. Chronic but not acute treatment with the antidepressant fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), suppressed the enhancement of DOI-induced HTR after OBX.. These findings indicate that OBX, and the subsequent degeneration of neurons projecting from the olfactory bulb, caused a supersensitivity of 5-HT(2A/2C) receptors which may be involved in symptoms of depression.

Topics: Amphetamines; Animals; Behavior, Animal; Depressive Disorder; Disease Models, Animal; Fluvoxamine; Head Movements; Male; Mice; Olfactory Bulb; Receptor, Serotonin, 5-HT2C; Selective Serotonin Reuptake Inhibitors; Serotonin 5-HT2 Receptor Antagonists

Topics: Depressive Disorder; Duloxetine Hydrochloride; Dyskinesia, Drug-Induced; Female; Fluvoxamine; Humans; Middle Aged; Selective Serotonin Reuptake Inhibitors; Thiophenes; Treatment Outcome

Akathisia is a syndrome characterized by the unpleasant sensation of "inner" restlessness that manifests itself in the inability of sitting still or not moving. Many types of medicaments can cause akathisia as an adverse event of their use and they include: antipsychotics, antidepressants, antiemetics, antihistamines, and psychoactive substances. We will present the case of a 50 year old patient, treated on two occasions for psychotic depression. During the second hospitalization it is possible that antipsychotic treatment combined with an antidepressant caused akathisia or there were symptoms of agitated depression and akathisia present at the same time, which is very difficult to determine in everyday clinical practice. We can conclude that in this case, as in many others, akathisia as a possible adverse effect of psychopharmacs was very hard to identify. Therefore, it is necessary to have akathisia in mind when using certain medicaments, especially when combining several that use the same enzymatic system and consequently raise levels of at least one of them.

Topics: Affective Disorders, Psychotic; Akathisia, Drug-Induced; Anticonvulsants; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Depressive Disorder; Diagnosis, Differential; Diagnostic Errors; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Fluvoxamine; Humans; Male; Middle Aged; Olanzapine; Psychomotor Agitation; Quetiapine Fumarate; Valproic Acid

Topics: Antidepressive Agents, Second-Generation; Brain; Depressive Disorder; Dyskinesias; Fluvoxamine; Humans; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Male; Middle Aged; Radiography

To examine characteristics of drop-outs from treatment for obsessive-compulsive disorder (OCD), we studied 121 participants who underwent exposure or cognitive treatment, either alone or with fluvoxamine. OCD symptoms were assessed at pre-treatment, post-treatment, and at every session. No differences in attrition were found between treatment conditions. Drop-outs from treatment (n=31) were divided into early (before session 6) and late (session 6 or after) drop-outs. We found that early drop-outs had more severe OCD symptoms at termination compared to completers, whereas late drop-outs did not differ from treatment completers. Higher levels of depressive symptoms were associated with early drop-outs, and lower levels with completers. These findings suggest that individuals with high levels of pretreatment depression are at risk for early drop-out with elevated OCD symptoms. Conversly, late drop-outs may be treatment responders who drop out after experiencing substantial improvement. Implications for allocation of resources for attrition prevention are discussed.

Topics: Adult; Anti-Anxiety Agents; Cognitive Behavioral Therapy; Combined Modality Therapy; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Middle Aged; Obsessive-Compulsive Disorder; Patient Dropouts; Randomized Controlled Trials as Topic; Treatment Outcome

Duloxetine is a potent and selective inhibitor of serotonin and norepinephrine reuptake with weak activity on dopamine reuptake. Enzymes involved in duloxetine metabolism are cytochrome P450 isoenzymes (CYP) CYP1A2 and to a lesser extent CYP2D6 whereas the selective serotonin reuptake inhibitor Fluvoxamine is known to be a potent inhibitor of CYP1A2. Changes in plasma levels of duloxetine revealing pharmacokinetic interactions with fluvoxamine, clinical effects and adverse effects of adding fluvoxamine in thirteen patients with a steady-state duloxetine treatment by intraindividual comparisons were analyzed in this retrospective survey. Patients had been treated with duloxetine under steady-state conditions until fluvoxamine was added. Plasma duloxetine levels were measured at steady state of different daily doses due to lacking experience with the combination of DLX and FLX. Adding 25 mg of fluvoxamine (FLX) per day to a steady-state treatment with 30 mg of duloxetine (DLX) in 8 patients led to an average increase of duloxetine plasma levels that was 3-fold with a magnitude of 50-506%. Our findings indicate that duloxetine plasma levels can be enhanced by a potent CYP1A2 inhibition by FLX and that DLX, even in higher plasma levels, seems to be well tolerated. The use of combined treatments, however, underscores the importance of understanding pharmacokinetic interactions.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Depressive Disorder; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Duloxetine Hydrochloride; Female; Fluvoxamine; Humans; International Classification of Diseases; Male; Middle Aged; Retrospective Studies; Thiophenes

The objective of this study was to assess the risk of suicide attempts and suicides after initiation of antidepressant medication use by children and adolescents, for individual agents.. We conducted a 9-year cohort study by using population-wide data from British Columbia. We identified new users of antidepressants who were 10 to 18 years of age with a recorded diagnosis of depression. Study outcomes were hospitalization attributable to intentional self-harm and suicide death.. Of 20,906 children who initiated antidepressant therapy, 16,774 (80%) had no previous antidepressant use. During the first year of use, we observed 266 attempted and 3 completed suicides, which yielded an event rate of 27.04 suicidal acts per 1000 person-years (95% confidence interval [CI]: 23.9-30.5 suicidal acts per 1000 person-years). There were no meaningful differences in the rate ratios (RRs) comparing fluoxetine with citalopram (RR: 0.97 [95% CI: 0.54-1.76]), fluvoxamine (RR: 1.05 [95% CI: 0.46-2.43]), paroxetine (RR: 0.80 [95% CI: 0.47-1.37]), and sertraline (RR: 1.02 [95% CI: 0.56-1.84]). Tricyclic agents showed risks similar to those of selective serotonin reuptake inhibitors (RR: 0.92 [95% CI: 0.43-2.00]).. Our finding of equal event rates among antidepressant agents supports the decision of the Food and Drug Administration to include all antidepressants in the black box warning regarding potentially increased suicidality risk for children and adolescents beginning use of antidepressants.

Topics: Adolescent; Antidepressive Agents; Child; Citalopram; Cohort Studies; Cross-Sectional Studies; Depressive Disorder; Female; Fluoxetine; Fluvoxamine; Humans; Male; Paroxetine; Risk Factors; Selective Serotonin Reuptake Inhibitors; Sertraline; Suicide; Suicide Prevention; Suicide, Attempted

A US Food and Drug Administration advisory has warned that antidepressants may be associated with an increased risk of suicidal thoughts and behaviors in adolescents. This prompted a meta-analysis of trials in adults that found no overall increase in risk, but individual agents could not be studied.. To assess the risk of suicide and suicide attempts associated with individual antidepressant agents.. Cohort study of incident users of antidepressant agents.. Population-based health care utilization data of all residents of British Columbia, Canada, aged 18 years and older between January 1, 1997, and December 31, 2005.. British Columbia residents who had antidepressant therapy initiated and had a recorded diagnosis of depression.. Initiation of various antidepressant medications.. Combined suicide death or hospitalization due to self-harm.. In a population of 287,543 adults aged 18 years and older with antidepressant therapy initiated, we observed outcome rates ranging from 4.41/1000 person-years to 9.09/1000 person-years. Most events occurred in the first 6 months after treatment initiation. After extensive propensity score adjustment, we found no clinically meaningful variation in the risk of suicide and suicide attempt between antidepressant agents compared with fluoxetine hydrochloride initiation: citalopram hydrobromide, hazard ratio = 1.00 (95% confidence interval, 0.63-1.57); fluvoxamine maleate, hazard ratio = 0.98 (95% confidence interval, 0.63-1.51); paroxetine hydrochloride, hazard ratio = 1.02 (95% confidence interval, 0.77-1.35); and sertraline hydrochloride, hazard ratio = 0.75 (95% confidence interval, 0.53-1.05). Compared with selective serotonin reuptake inhibitors as a drug class, other classes including serotonin-norepinephrine reuptake inhibitors, tricyclic agents, and other newer and atypical agents had a similar risk. Restriction to patients with no antidepressant use in the past 3 years further reduced apparent differences between groups.. Our finding of equal event rates across antidepressant agents supports the US Food and Drug Administration's decision to treat all antidepressants alike in their advisory. Treatment decisions should be based on efficacy, and clinicians should be vigilant in monitoring after initiating therapy with any antidepressant agent.

Topics: Adult; Aged; Antidepressive Agents; British Columbia; Cause of Death; Citalopram; Cohort Studies; Depressive Disorder; Female; Fluoxetine; Fluvoxamine; Hospitalization; Humans; Male; Middle Aged; Paroxetine; Proportional Hazards Models; Risk; Selective Serotonin Reuptake Inhibitors; Suicide; Suicide, Attempted

The catechol-O-methyltransferase (COMT) enzyme inactivates catecholamines, and the COMT Val(108/158)Met polymorphism (rs4680) influences the enzyme activity. Recent clinical studies found a significant effect of rs4680 on antidepressant response to fluoxetine and paroxetine, but several other studies were negative. No study considered drug plasma levels as possible nuisance covariate.. We studied the effect of rs4680 on response to fluvoxamine antidepressant monotherapy.. Forty-one consecutively admitted inpatients affected by a major depressive episode in course of major depressive disorder were administered fluvoxamine for 6 weeks. Changes in severity of depression were assessed with weekly Hamilton Depression ratings and analyzed with repeated measures ANOVA in the context of General Linear Model, with rs4680 and fluvoxamine plasma levels as factors.. rs4680 significantly interacted with time in affecting antidepressant response to fluvoxamine, with outcome being inversely proportional to the enzyme activity: better effects in Met-carriers, worse effects in Val/Val homozygotes. The effect became significant at the fourth week of treatment, and influence final response rates. Fluvoxamine plasma levels had marginal effects on outcome.. This is the first study that reports a positive effect of rs4680 on response to fluvoxamine, and the third independent report of its influence on response to selective 5-HT reuptake inhibitors (SSRIs). Our findings support the hypothesis that factors affecting catecholaminergic neurotransmission might contribute to shape the individual response to antidepressants irrespective of their primary molecular target.

Topics: Adult; Aged; Alleles; Antidepressive Agents, Second-Generation; Catechol O-Methyltransferase; Depressive Disorder; Female; Fluvoxamine; Gene Frequency; Genotype; Humans; Logistic Models; Male; Middle Aged; Polymorphism, Single Nucleotide; Severity of Illness Index; Treatment Outcome

We examined whether discontinuation and the responses to fluvoxamine (FLV) administration could predict the subsequent discontinuation and the responses to paroxetine (PRX) in patients with depression.. The subjects comprised 106 outpatients who were diagnosed with depression, and clinical evaluation was conducted every 2 weeks. Patients who discontinued FLV because of side effects or did not achieve remission with 200 mg/day of FLV, the drug was switched to PRX. The maximum dose of PRX was 40 mg/day.. Among 10 patients who discontinued FLV, PRX was also discontinued in one patient. Of 33 patients without remission on FLV, PRX was discontinued because of side effects in two patients. There was no statistical difference in the discontinuation rates between the two groups. Four of 10 patients who discontinued FLV achieved remission, while nine of 33 patients without remission with FLV achieved remission with PRX. The remission rate was not significantly different between the two groups.. Discontinuation and the responses related to FLV could not serve as a predictor for the subsequent discontinuation and the responses related to PRX.

Topics: Adult; Depression; Depressive Disorder; Drug Substitution; Female; Fluvoxamine; Humans; Male; Middle Aged; Paroxetine; Treatment Outcome; Young Adult

Oxidative stress is a critical route of damage in various psychological stress-induced disorders, such as depression. Antidepressants are widely prescribed to treat these conditions; however, few animal studies have investigated the effect of these drugs on endogenous antioxidant status in the brain. The present study employed a 21-day chronic regimen of random exposure to restraint stress to induce oxidative stress in brain, and behavioural aberrations, in rodents. The forced swimming (FST) and sucrose preference tests were used to identify depression-like phenotypes, and reversal in these indices indicated the effectiveness of treatment with fluoxetine (FLU; 20 mg/kg/day, p.o.; selective serotonin reuptake inhibitor), imipramine (IMI; 10 mg/kg/day, p.o.; tricyclic antidepressant) and venlafaxine (VEN; 10 mg/kg/day, p.o.; dual serotonin/norepinephrine reuptake inhibitor) following restraint stress. The antioxidant status was investigated in the brain of these animals. The results evidenced a significant recovery in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione reductase (GR) and glutathione (GSH) levels by antidepressant treatments following a restraint stress-induced decline of these parameters. The severely accumulated lipid peroxidation product malondialdehyde (MDA) and protein carbonyl contents in stressed animals were significantly normalized by antidepressant treatments. The altered oxidative status is implicated in various aspects of cellular function affecting the brain. Thus, it is possible that augmentation of in vivo antioxidant defenses could serve as a convergence point for multiple classes of antidepressants as an important mechanism underlying the neuroprotective pharmacological effects of these drugs observed clinically in the treatment of various stress disorders. Consequently, pharmacological modulation of stress-induced oxidative damage as a possible stress-management approach should be an important avenue of further research.

Topics: Animals; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Antioxidants; Body Weight; Cyclohexanols; Depressive Disorder; Fluvoxamine; Food Preferences; Imipramine; Lipid Peroxidation; Protein Carbonylation; Rats; Restraint, Physical; Stress, Psychological; Swimming; Taste; Venlafaxine Hydrochloride

Use of antidepressants has been reported to cause considerable weight gain. The aim of this study was to assess the risk of diabetes mellitus associated with antidepressant treatment and to examine whether the risk is influenced by treatment duration or daily dose.. This was a nested case-control study in a cohort of 165,958 patients with depression who received at least one new prescription for an antidepressant between January 1, 1990, and June 30, 2005. Data were from from the U.K. General Practice Research Database. Patients were at least 30 years of age and without diabetes at cohort entry.. A total of 2,243 cases of incident diabetes mellitus and 8,963 matched comparison subjects were identified. Compared with no use of antidepressants during the past 2 years, recent long-term use (>24 months) of antidepressants in moderate to high daily doses was associated with an increased risk of diabetes (incidence rate ratio=1.84, 95% CI=1.35-2.52). The magnitude of the risk was similar for long-term use of moderate to high daily doses of tricyclic antidepressants (incidence rate ratio=1.77, 95% CI=1.21-2.59) and selective serotonin reuptake inhibitors (incidence rate ratio=2.06, 95% CI=1.20-3.52). Treatment for shorter periods or with lower daily doses was not associated with an increased risk.. Long-term use of antidepressants in at least moderate daily doses was associated with an increased risk of diabetes. This association was observed for both tricyclic antidepressants and selective serotonin reuptake inhibitors.

Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Body Mass Index; Case-Control Studies; Cyclohexanols; Depressive Disorder; Diabetes Mellitus; Female; Fluvoxamine; Humans; Incidence; Male; Middle Aged; Paroxetine; Risk Factors; Selective Serotonin Reuptake Inhibitors; Time Factors; United Kingdom; Venlafaxine Hydrochloride

The 5-HT2A receptor is a key modulator of the serotonin pathway. We previously observed a marginal association between 5-HT2A gene variants and antidepressant efficacy in Japanese and Italian population but in the opposite direction. In the present report, we hypothesize that discrepant findings on 5-HT2A gene variants could be due to both the effect of ethnicity and a possible specific effect on some symptom improvement. The sample comprised 203 patients affected by mood disorders and treated for major depression with paroxetine or fluvoxamine. The total depressive scores for all patients were analyzed in previous reports, but symptomatologic clusters were not examined previously. The 21-item Hamilton Rating Scale for Depression (HAM-D) was administered to evaluate depressive symptoms at baseline and bi-weekly over 6 weeks of treatment. All patients were genotyped for the 5-HT2A T102C polymorphism. Compared with patients with the 5-HT2A T and C variants, in the Japanese sample T allele carriers showed selective and slower score reductions than C allele carriers in delusion and activity symptoms; on the other hand, in the Italian sample, C allele carriers showed a slower and selective score reduction compared with T allele carriers in Somatic anxiety, while they did not differ from other patients on the other scores. Despite the limitations of the small sample size and modest significance levels, these findings suggest that response to SSRIs is not a unitary phenomenon and discrepant findings across ethnic groups may be due to differential effects of gene variants.

Topics: Adult; Antidepressive Agents; Asian People; Depressive Disorder; Depressive Disorder, Major; Female; Fluvoxamine; Gene Frequency; Genetic Variation; Genotype; Humans; Italy; Male; Middle Aged; Paroxetine; Pharmacogenetics; Polymorphism, Single Nucleotide; Receptor, Serotonin, 5-HT2A; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; White People

The aim of this study was to examine the psychopharmacological effects of antidepressants on post-ischemic rats. Global transient cerebral ischemia was performing with the four-vessels occlusion method. Locomotor activity, neurological scores and activity during the 20 min forced swimming test (FST) session were comparatively evaluated in sham-operated and ischemic animals. Three doses of four antidepressants or saline were then intraperitoneally administered 23.5, 5 and 1h before the 5 min FST session, and 0.5h before the elevated plus-maze (EPM). Histological quantification of neuronal loss was performed at the end of the experiments. Results show that before treatment, ischemic animals present significantly greater spontaneous motor activity, a neurological score and an immobility time in the 20 min FST lower than sham-operated animals. After treatment, compared to the saline group, we show an antidepressant-like activity in the FST with all the molecules, except with the fluvoxamine, and an anxiolytic-like effect in the EPM, with at least one dose of each compounds. The observed effect is very similar according to whether or not the animals were ischemic, with a tendency to react more important for ischemic animals versus sham-operated. This difference is significant in the FST for the immobility time and in the EPM for the ratio of distance, of time, of number of entrances and non-protected head dips with the 45 mg dose of milnacipran. These results demonstrate that even though global transient cerebral ischemia induces important cerebral lesions, it modifies little the effects of the different antidepressants, whatever their primary pharmacological target, with a particular effectiveness with the dual serotonin and norepinephrine reuptake inhibitor milnacipran.

Topics: Analysis of Variance; Animals; Antidepressive Agents; Anxiety Disorders; Behavior, Animal; Brain Ischemia; Cyclopropanes; Depressive Disorder; Desipramine; Disease Models, Animal; Dose-Response Relationship, Drug; Exploratory Behavior; Fluvoxamine; Hippocampus; Imipramine; Immobility Response, Tonic; Male; Milnacipran; Motor Activity; Rats; Rats, Wistar

There are a lot of studies on depressive disorders in a general hospital done across the world, but no data from Russia on this subject was found in international psychiatric journals or MEDLINE.. to determine the prevalence of depressive disorders in medical inpatients in Izhevsk, the capital of the Udmurt Republic, a region in Russia, and to identify associated factors.. A sample of 323 adult medical inpatients was composed. The Russian version of the MINI 5.0.0 was used.. The prevalence of lifetime and current depressive disorders was 30% and 20.7%, respectively. Depression was more common in women, widowed or divorced, retired or disabled, with low income and bad family relationships, and among respondents with a chronic somatic illness. Depression had a high comorbidity with organic mental and anxiety disorders. Only 40.3% of the individuals with depression had referred for psychiatric consultations, most of them being treated with fluvoxamine.. Prevalence of depression was substantial but consistent with other studies. Taking into consideration associated factors, physicians can improve recognition and treatment of depression in medical inpatients.

Topics: Adolescent; Adult; Antidepressive Agents, Second-Generation; Anxiety Disorders; Comorbidity; Cross-Cultural Comparison; Cross-Sectional Studies; Depressive Disorder; Female; Fluvoxamine; Hospitals, General; Humans; Male; Mental Disorders; Middle Aged; Neurocognitive Disorders; Referral and Consultation; Russia; Socioeconomic Factors; Young Adult

Therapeutic drug monitoring studies of selective serotonin reuptake inhibitor (SSRI) antidepressants thus far failed to identify a clear concentration-response relationship in major depression. Majority of the previous studies defined clinical response as 50% or greater reduction from baseline in depression rating scale scores. Because many patients who meet these criteria still present symptoms associated with functional impairment, there is a need to consider "remission" as an alternative end point in concentration-response analyses of SSRIs. The present 12-week prospective study investigated the relationship between fluvoxamine (an SSRI) plasma concentration and remission in outpatients with depression. We used a flexible dose titration study designed to mimic clinical practice within the therapeutic dose range of fluvoxamine (25-200 mg/d). Receiver operating characteristics (ROC) curve was computed to determine the optimal fluvoxamine plasma concentration for remission using 269 concentration data obtained from 80 patients. Analysis of the ROC curve from the entire study sample did not reveal a fluvoxamine concentration significantly predicting remission. By contrast, ROC analysis specifically in patients with moderate to severe depression (N = 51; baseline 17-item Hamilton Rating Scale for Depression score > or = 20) found a fluvoxamine concentration of 61.4 ng/mL as a significant predictor of remission. In conclusion, therapeutic drug monitoring may be useful for rational titration and individualization of fluvoxamine dose and predicting remission in patients with moderate to severe depression, who may presumably display lesser placebo component in pharmacodynamic response.

Topics: Adjustment Disorders; Adult; Antidepressive Agents, Second-Generation; Depressive Disorder; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluvoxamine; Humans; Male; Middle Aged; Personality Inventory; Prospective Studies; ROC Curve; Treatment Outcome

A growing body of evidence suggests a disturbance of brain plasticity in major depression. In contrast to hippocampal neurogenesis, much less is known about the role of synaptic plasticity. Long-term potentiation (LTP) and long-term depression (LTD) regulate the strength of synaptic transmission and the formation of new synapses in many neural networks. Therefore, we examined the modulation of synaptic plasticity in the chronic mild stress animal model of depression.. Adult rats were exposed to mild and unpredictable stressors for 3 weeks. Thereafter, long-term synaptic plasticity was examined in the hippocampal CA1 region by whole-cell patch clamp measurements in brain slices. Neurogenesis was assessed by doublecortin immunostaining.. Exposure to chronic mild stress facilitated LTD and had no effect on LTP. Chronic application of the antidepressant fluvoxamine during the stress protocol prevented the facilitation of LTD and increased the extent of LTP induction. Neurogenesis in the dentate gyrus was impaired after chronic stress.. In addition to neurogenesis, long-term synaptic plasticity is an important and ubiquitous form of brain plasticity that is disturbed in an animal model of depression. Facilitated depression of synaptic transmission might impair function and structure of brain circuits involved in the pathophysiology of major depression. Antidepressants might counteract these alterations.

Topics: Animals; Chronic Disease; Dentate Gyrus; Depressive Disorder; Disease Models, Animal; Doublecortin Protein; Fluvoxamine; Hippocampus; Long-Term Potentiation; Long-Term Synaptic Depression; Neuronal Plasticity; Patch-Clamp Techniques; Rats; Rats, Wistar; Stress, Psychological; Synaptic Transmission

The efficacy of the addition of lithium to an established course of antidepressant treatment can be explained by a synergistic effect of the two drugs on central 5-HT neurotransmission. In the present study we investigated the effect of lithium addition on the 5-HT concentration in plasma and platelets and the concentration of 5-HIAA. Thirty-nine depressed inpatients who fulfilled the DSM-IV criteria for major depressive disorder and who did not respond to monotherapy with either imipramine or fluvoxamine participated in this study. Concentration of 5-HT in both plasma and platelets did not change significantly during lithium addition. The 5-HT ratio (plasma concentration/platelet concentration) shows a small non-significant increase after 3 weeks lithium addition. The mean concentration of 5-HIAA shows a significant increase during lithium addition; with no difference between the imipramine and the fluvoxamine sample. The increments in 5-HIAA concentration during lithium addition are indicative of an increased 5-HT turnover.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Antimanic Agents; Blood Platelets; Depressive Disorder; Drug Resistance; Female; Fluvoxamine; Humans; Hydroxyindoleacetic Acid; Imipramine; Lithium Compounds; Male; Middle Aged; Psychiatric Status Rating Scales; Serotonin

Topics: Adult; Anti-Bacterial Agents; Antidepressive Agents, Second-Generation; Clindamycin; Depressive Disorder; Drug Interactions; Dyskinesia, Drug-Induced; Fluvoxamine; Humans; Male

Topics: Adult; Affective Disorders, Psychotic; Antipsychotic Agents; Breast Feeding; Depression, Postpartum; Depressive Disorder; Dibenzothiazepines; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Fluvoxamine; Humans; Pregnancy; Pregnancy Complications; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors

A functional insertion/deletion (*l/*s) repeat polymorphism within the promoter region of the serotonin transporter (5-HTTLPR) has been described. An association between *l variant and a better and faster response to serotonin selective reuptake inhibitors in depressed patients was reported in Caucasians. The value of the explained variance due to the 5-HTTLPR, however, was 7% only, and different *l and *s variants were reported according to the nucleotide sequence of repeats. In this study, we investigated the antidepressant response to fluvoxamine in individuals carrying different *l and *s variants according to the Nakamura findings. Two hundred and twenty-eight patients affected by bipolar disorder and major depression were administered a daily dose of fluvoxamine up to 300 mg and evaluated at baseline and weekly thereafter until week 7, using the 21-item Hamilton Rating Scale for Depression. We found a marginally significant difference in genotype and allele (P=0.04, data not shown) distribution (*l and *s traditional variants) according to diagnosis (bipolar disorder vs. major depression). We confirmed a better and faster response in our depressed patients bearing the *l variant, but we also found significant differences in response among *l carriers according to the type of *l allele. In fact, 16F *l carriers showed only a partial response, while 16D *l carriers showed a marginally significantly better response than 16A *l allele carriers. These results, although very preliminary, can represent a further step toward a better understanding of the molecular genetics of antidepressant response.

Topics: Adult; Base Sequence; Bipolar Disorder; Depressive Disorder; DNA; DNA Primers; Female; Fluvoxamine; Gene Frequency; Genetic Carrier Screening; Genetic Variation; Humans; Male; Middle Aged; Polymorphism, Genetic; Repetitive Sequences, Nucleic Acid; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins

Tetrahydrobiopterin (BH4) is a coenzyme of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), rate-limiting enzymes of monoamine biosynthesis. According to the monoamine hypothesis of depression, antidepressants will restore the function of the brain monoaminergic system, and BH4 concentration.. To investigate the effects of fluvoxamine on BH4 levels and dopamine (DA) and serotonin (5-HT) turnover in the mesoprefrontal system, incorporating two risk factors of depression, social isolation and acute environmental change.. Male ddY mice (6W) were divided into two housing groups, i.e. group-housing (eight animals per cage; 35 days), and isolation-housing (one per cage; 35 days), SC injected with fluvoxamine (20 or 40 mg/kg; days 29-35), and exposed to 20-min novelty stress (day 35). The levels of BH4, DA, homovanilic acid (HVA), 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the prefrontal cortex and midbrain.. Under the group-housing condition, novelty stress significantly increased BH4 levels in both regions, and the HVA/DA ratio in the midbrain, whereas it did not change any parameters in either region under the isolation-housing condition. In the prefrontal cortex, fluvoxamine significantly decreased the 5-HIAA/5-HT ratio under the group-housing condition, and BH4 levels and the HVA/DA ratio under the isolation-housing condition. In the midbrain, fluvoxamine significantly decreased all parameters, except for an increasing in the 5-HIAA/5-HT ratio under the isolation-housing condition.. Isolation-housing suppressed the increase of BH4 levels and DA turnover elicited by novelty stress. Fluvoxamine suppressed BH4 levels, and DA and 5-HT turnover. Fluvoxamine may have altered DA turnover by suppressing BH4 levels.

Topics: Animals; Biopterins; Depressive Disorder; Dopamine; Fluvoxamine; Housing, Animal; Injections, Subcutaneous; Male; Membrane Glycoproteins; Membrane Transport Proteins; Mesencephalon; Mice; Mice, Inbred Strains; Nerve Tissue Proteins; Prefrontal Cortex; Selective Serotonin Reuptake Inhibitors; Serotonin; Serotonin Plasma Membrane Transport Proteins; Social Isolation

Topics: Adult; Chemical and Drug Induced Liver Injury; Citalopram; Depressive Disorder; Female; Fluvoxamine; Hepatorenal Syndrome; Humans; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic

Mutant R406W human tau was originally identified in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and causes a hereditary tauopathy that clinically resembles Alzheimer's disease (AD). In the current study, we examined the performance of R406W transgenic (Tg) mice in the forced swimming test, a test with high predictivity of antidepressant efficacy in human depression, and found an enhancement of the immobility time. In contrast, the motor function and anxiety-related emotional response of R406W Tg mice were normal. Furthermore, a selective serotonin reuptake inhibitor (SSRI), fluvoxamine (100 mg/kg, p.o.), significantly reduced this enhancement of the immobility time, whereas a noradrenaline reuptake inhibitor, desipramine, had no effect. In an in vivo microdialysis study, R406W Tg mice exhibited a significantly decreased extracellular 5-hydroxyindoleacetic acid (5-HIAA) level in the frontal cortex and also exhibited a tendency toward a decreased extracellular 5-hydroxytryptamine (5-HT) level. Moreover, fluvoxamine, which reduced the enhancement of the immobility time, significantly increased the extracellular 5-HT level in R406W Tg mice. These results suggest that R406W Tg mice exhibit changes in depression-related behavior involving serotonergic neurons and provide an animal model for investigating AD with depression.

Topics: Alzheimer Disease; Animals; Behavior, Animal; Brain Chemistry; Depressive Disorder; Disease Models, Animal; Extracellular Fluid; Fluvoxamine; Humans; Hydroxyindoleacetic Acid; Mice; Mice, Transgenic; Microdialysis; Motor Activity; Mutation; Neurons; Raphe Nuclei; Selective Serotonin Reuptake Inhibitors; Serotonin; Swimming; tau Proteins; Up-Regulation

Seven Japanese patients on maintenance hemodialysis who were comorbid with mild depression were medicated with 50 mg/day fluvoxamine maleate for 28 days. Effectiveness was obtained in four out of seven patients (57%). The plasma fluvoxamine concentrations were examined in three patients. The plasma fuvoxamine concentration decreased by 22% by hemodialysis. There is a tendency for the dialyzed rate of fluvoxamine to become lower if the plasma albumin concentration is higher. The half-life of fluvoxamine was possibly shortened more in the patient with hypoalbuminaemia. The plasma fluvoxamine concentration reached a steady state 8 days after the start of medication and thereafter. The time required to reach steady state was lengthened when compared with the results in normal Japanese volunteers.

Topics: Antidepressive Agents, Second-Generation; Biological Availability; Depressive Disorder; Diabetic Nephropathies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluvoxamine; Half-Life; Humans; Japan; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Middle Aged; Personality Inventory; Renal Dialysis; Treatment Outcome

Beta-arrestins play a pivotal role in G protein-coupled receptor desensitization. beta-Arrestins interfere in G protein receptor interaction, thus leading to desensitization of G protein-mediated receptor signaling. G protein receptor signaling and its desensitization were previously implicated in the pathophysiology of mood disorders and in the mechanism of action of antidepressant and mood-stabilizing treatments. The present study aims at quantitatively evaluating beta-arrestin-1 levels in leukocytes of patients with major depression and the effect of antidepressants on beta-arrestin-1 levels in rat brain.. Beta-arrestin-1 measurements were carried out in cortical, hippocampal, and striatal brain regions of rats chronically intragastrically treated with either imipramine, desipramine, or fluvoxamine. Similar measurements were conducted in mononuclear leukocytes of 36 untreated patients with major depression and 32 healthy volunteer subjects. Beta-arrestin-1 levels were evaluated through immunoblot analyses using monoclonal antibodies to beta-arrestin-1.. Beta-arrestin-1 levels were significantly elevated by all three antidepressants in rat cortex and hippocampus, while in the striatum no alterations could be detected. This process became significant within 10 days and took 2-3 weeks to reach maximal increase. Mononuclear leukocytes of patients with depression showed significantly reduced immunoreactive quantities of beta-arrestin-1. The reduction in beta-arrestin-1 levels was significantly correlated with the severity of depressive symptoms.. The findings in the rat study suggest beta-arrestin-1 elevation as a biochemical mechanism for antidepressant-induced receptor down-regulation. The findings in human subjects support the implication of beta-arrestin-1 in the pathophysiology of mood disorders. Beta-arrestin-1 measurements in patients with depression may potentially serve as a biochemical marker for depression.

Topics: Adult; Aged; Animals; Antidepressive Agents; Arrestins; beta-Arrestin 1; beta-Arrestins; Brain Chemistry; Cerebral Cortex; Corpus Striatum; Depressive Disorder; Desipramine; Down-Regulation; Female; Fluvoxamine; Hippocampus; Humans; Imipramine; Leukocytes, Mononuclear; Male; Middle Aged; Psychiatric Status Rating Scales; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Severity of Illness Index

Topics: Adult; Bipolar Disorder; Depressive Disorder; Female; Fluvoxamine; Humans; Methamphetamine; Selective Serotonin Reuptake Inhibitors; Substance Withdrawal Syndrome

Topics: Antidepressive Agents, Second-Generation; Depressive Disorder; Diabetes Mellitus; Female; Fluvoxamine; Humans; Hyperglycemia; Middle Aged

An 82-year-old man with treatment-resistant depression and early Alzheimer's disease was started on methylphenidate. Significant obsessive-compulsive behavior ensued but diminished over several weeks when methylphenidate was replaced by fluvoxamine. The patient had no prior psychiatric history, but he had a sister with obsessive-compulsive disorder. It appears that methylphenidate precipitated the patient's pathological behavior.

Topics: Aged; Aged, 80 and over; Anti-Anxiety Agents; Antidepressive Agents, Second-Generation; Anxiety Disorders; Buspirone; Central Nervous System Stimulants; Depressive Disorder; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fluvoxamine; Follow-Up Studies; Humans; Male; Methylphenidate; Obsessive-Compulsive Disorder

A 61-year-old patient with major depression and selective serotonin reuptake inhibitor-induced bruxism was successfully treated with a course of bilateral electroconvulsive therapy. Both the depressive symptoms and bruxism completely remitted after six treatments. Possible mechanisms of this effect are discussed.

Topics: Antidepressive Agents, Second-Generation; Bruxism; Depressive Disorder; Electroconvulsive Therapy; Female; Fluvoxamine; Humans; Middle Aged; Treatment Outcome

The effects of the 5-HT(2) receptor antagonist, LY 53857 on the effects of noradrenaline and serotonin reuptake inhibitors were investigated using the forced swimming test. LY 53857 enhanced anti-immobility effects of clomipramine and maprotiline, which can inhibit reuptake of noradrenaline. However, LY 53857 did not affect the immobility time of mice treated with the selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine. These results suggest that antagonism of the 5-HT(2) receptor leads to potentiation of the antidepressant effects of noradrenaline reuptake inhibitors but not SSRIs and that LY 53857 may modify the activity of noradrenergic neurons.

Topics: Adrenergic Uptake Inhibitors; Animals; Brain; Clomipramine; Depressive Disorder; Dose-Response Relationship, Drug; Drug Interactions; Ergolines; Fluoxetine; Fluvoxamine; Male; Maprotiline; Mice; Motor Activity; Neurons; Norepinephrine; Receptors, Serotonin; Selective Serotonin Reuptake Inhibitors; Serotonin; Serotonin Antagonists; Synaptic Transmission

Monoamine oxidase A (MAOA) and tryptophan hydroxylase (TPH) are the staple enzymes in the metabolism of serotonin (5-HT). The genetic polymorphisms of these two enzymes might individually alter the production, release, reuptake or degradation of 5-HT during the treatment of selective serotonin reuptake inhibitors (SSRIs), leading to the individual differences in the antidepressant effects of SSRIs. The authors investigated whether a functional polymorphism in the MAOA gene promoter (MAOA-VNTR) and a TPH gene polymorphism in intron 7 (TPH-A218C) were associated with the antidepressant response to fluvoxamine in 66 Japanese patients with major depressive disorder during a 6-week study with a specific dosage plan. Fifty-four patients completed the study. The present study fails to demonstrate that the genetic polymorphisms of MAOA-VNTR and TPH-A218C affect the antidepressant effect of fluvoxamine in Japanese patients with major depressive disorder.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Depressive Disorder; Female; Fluvoxamine; Humans; Japan; Male; Middle Aged; Monoamine Oxidase; Polymorphism, Genetic; Promoter Regions, Genetic; Treatment Outcome; Tryptophan Hydroxylase

We attempted to compare the antidepressant efficacy of milnacipran and fluvoxamine in 202 outpatients with major depression, using the 17-item Hamilton Depression Rating Scale (HDRS). Special attention was paid to the difference of responsiveness as a function of the severity of depression and individual HDRS factors. As a result, while no significant difference between the treatment groups was found overall, a positive response (50% or more decrease in total score from the baseline) was recorded significantly more often with milnacipran than fluvoxamine recipients whose baseline HDRS total score was greater than 19 points. Furthermore, there was a significant difference of response for the 'agitation' and 'insomnia' factors in favour of milnacipran. In both treatment groups, the incidence of adverse events, characteristic of tricyclic antidepressants such as dry mouth, constipation, somnolence and postural hypotension, was low. While complaints concerning the upper intestinal tract, such as epigastric distress, were predominant in the fluvoxamine group, urological complications and palpitations were reported only in the milnacipran group. In conclusion, we suggest that milnacipran is preferred to selective serotonin reuptake inhibitors for the treatment of depressed patients with agitation as well as severely depressed patients.

Topics: Adult; Antidepressive Agents, Second-Generation; Case-Control Studies; Cyclopropanes; Depressive Disorder; Female; Fluvoxamine; Humans; Individuality; Male; Milnacipran; Patient Dropouts; Psychiatric Status Rating Scales; Psychomotor Agitation

Pediatric populations, including those with autistic disorder or other pervasive developmental disorders, increasingly are being prescribed selective serotonin reuptake inhibitors (SSRIs). Little is known about the age-related brain pharmacokinetics of SSRIs; there is a lack of data regarding optimal dosing of medications for children. The authors used fluorine magnetic resonance spectroscopy ((19)F MRS) to evaluate age effects on whole-brain concentrations of fluvoxamine and fluoxetine in children taking SSRIs.. Twenty-one pediatric subjects with diagnoses of autistic disorder or other pervasive developmental disorders, 6-15 years old and stabilized with a consistent dose of fluvoxamine or fluoxetine, were recruited for the study; 16 successfully completed the imaging protocol. Whole-brain drug levels in this group were compared to similarly acquired data from 28 adults.. A significant relationship between dose and brain drug concentration was observed for both drugs across the age range studied. Brain fluvoxamine concentration in the children was lower, consistent with a lower dose/body mass drug prescription; when brain concentration was adjusted for dose/mass, age effects were no longer significant. Brain fluoxetine concentration was similar between age groups; no significant age effects on brain fluoxetine drug levels remained after adjustment for dose/mass. Observations of brain fluoxetine bioavailability and elimination half-life also were similar between age groups.. These findings suggest that fluvoxamine or fluoxetine prescriptions adjusted for dose/mass are an acceptable treatment approach for medicating children with autistic disorder or other pervasive developmental disorders. It must be determined whether these findings can be generalized to other pediatric populations.

Topics: Adolescent; Adult; Age Factors; Autistic Disorder; Brain; Brain Chemistry; Child; Child Development Disorders, Pervasive; Depressive Disorder; Dose-Response Relationship, Drug; Fluorine; Fluoxetine; Fluvoxamine; Half-Life; Humans; Magnetic Resonance Spectroscopy; Middle Aged; Obsessive-Compulsive Disorder; Panic Disorder; Selective Serotonin Reuptake Inhibitors

There are reports that abrupt withdrawal of various selective serotonin re-uptake inhibitors, such as fluvoxamine, can elicit in patients various withdrawal symptoms. Fluvoxamine has been widely used in Japan for approximately 1 year. However, there have been no case reports of withdrawal symptoms following abrupt fluvoxamine discontinuation in Japan. The author reports a case where the abrupt discontinuation of fluvoxamine produced restlessness in a depressed patient. The restlessness disappeared soon after the reinstatement of treatment with fluvoxamine. This case report suggests that clinicians should carefully scrutinize a patient's compliance to fluvoxamine as the withdrawal symptoms observed following abrupt discontinuation might be regarded as a relapse of depression or side-effects of the medicine.

Topics: Adult; Depressive Disorder; Fluvoxamine; Humans; Male; Psychomotor Agitation; Selective Serotonin Reuptake Inhibitors; Substance Withdrawal Syndrome

Between 10% and 15% of new mothers will experience an episode of postpartum depression. Although antidepressants are effective agents for the treatment of postpartum depression, minimal data are available to support their safety in infants of breastfeeding mothers.. In this article, we present 2 cases of nursing mother-infant pairs in which the mother was treated with fluvoxamine and in which infant serum fluvoxamine levels were obtained. Both mothers began the fluvoxamine treatment postpartum, and serum levels were obtained from mothers and infants after a minimum of 7 days on a stable maternal dose. One level was obtained from the infant in case 1, and 2 levels were obtained from the infant in case 2.. Each of the infant serum fluvoxamine levels obtained was too low to quantify (at a limit of detection of 2.5 ng/mL). Neither of the infants experienced adverse events related to the mother's treatment with fluvoxamine. Each of the infants is reportedly healthy 2 to 3 years after the exposure.. While these results are encouraging, they are limited and cannot be generalized to all cases of infants exposed to fluvoxamine. Additional mother-infant serum fluvoxamine levels and infant behavioral observations will facilitate the risk-benefit decision-making process for women who choose to breast-feed while taking fluvoxamine.

Topics: Breast Feeding; Chromatography, High Pressure Liquid; Depressive Disorder; Female; Fluvoxamine; Humans; Infant, Newborn; Milk, Human; Risk Assessment; Selective Serotonin Reuptake Inhibitors

Topics: Cyclohexanols; Delusions; Depressive Disorder; Double-Blind Method; Fluvoxamine; Humans; Randomized Controlled Trials as Topic; Research Design; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride

Topics: Adult; Breast; Breast Diseases; Depressive Disorder; Female; Fluvoxamine; Humans; Hypertrophy; Mammography; Selective Serotonin Reuptake Inhibitors

Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Depressive Disorder; Drug Interactions; Female; Fluvoxamine; Humans; Olanzapine; Pirenzepine; Schizophrenia

Therapeutic drug monitoring data of the new atypical neuroleptic drug olanzapine were used to study interactions with the selective serotonin reuptake inhibitors fluvoxamine and sertraline. The distribution of the ratio of concentration/daily dose (C/D; ng/mL per mg/d) of olanzapine was compared in three groups: patients treated with olanzapine (n = 134), patients treated with olanzapine plus fluvoxamine (n = 10) concomitantly, and patients treated with olanzapine plus sertraline (n = 21) concomitantly. No significant difference was seen between the olanzapine and the olanzapine plus sertraline groups. Patients receiving fluvoxamine in addition to olanzapine had C/D ratios that were in the mean 2.3-fold higher than patients receiving olanzapine without additional fluvoxamine. This indicated that fluvoxamine inhibits the metabolism of olanzapine, probably because of inhibition of cytochrome P450 (CYP) 1A2, whereas sertraline is unlikely to interfere with the metabolism of olanzapine. Combination therapy of olanzapine and fluvoxamine should be used cautiously, and therapeutic drug monitoring should be instituted to avoid olanzapine-induced adverse effects or intoxications.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Benzodiazepines; Chromatography, High Pressure Liquid; Cytochrome P-450 Enzyme System; Depressive Disorder; Drug Interactions; Drug Monitoring; Female; Fluvoxamine; Humans; Liver; Male; Middle Aged; Olanzapine; Pirenzepine; Selective Serotonin Reuptake Inhibitors; Sertraline

To report two cases of interaction between fluvoxamine and mirtazapine.. A 17-year-old boy was treated with mirtazapine 30 mg/d. The addition of fluvoxamine 100 mg/d to the regimen caused a threefold increase in the mirtazapine concentration. This interaction was associated with increased anxiety. A second patient, a 43-year-old woman, was treated with mirtazapine 15 mg/d. There was a fourfold increase in her mirtazapine concentration and simultaneous mood improvements after augmentation with fluvoxamine 50 mg/d.. This is the first report of any interaction between fluvoxamine and mirtazapine. Mirtazapine is mainly metabolized by cytochrome P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4. Fluvoxamine and cimetidine Inhibit the same isoenzymes, but fluvoxamine is probably the only agent that causes a clinically significant interaction.. Adding fluvoxamine to treatment with mirtazapine may cause a significant increase in mirtazapine concentration. This interaction may necessitate adjustment of the mirtazapine dosage.

Topics: Adolescent; Adult; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Depressive Disorder; Drug Interactions; Female; Fluvoxamine; Gas Chromatography-Mass Spectrometry; Humans; Male; Mianserin; Mirtazapine

Topics: Aged; Anti-Inflammatory Agents; Antidepressive Agents, Second-Generation; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Middle Aged; Prednisolone

The authors present data from an open trial of fluvoxamine (median daily dosage: 200 mg) in the treatment of generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder in 19 older outpatients (mean age = 66.8). Of the 12 subjects completing the 21-week trial, 8 achieved a good response (50% reduction in symptom measures) and 7 were rated as much or very much improved. Fluvoxamine pharmacotherapy also had a significant effect in reducing comorbid depressive symptoms and in increasing levels of functioning. These data support the effectiveness of fluvoxamine in older subjects with anxiety disorders (particularly generalized anxiety disorder) and warrant further double-blind, placebo-controlled evaluation.

Topics: Aged; Ambulatory Care; Anxiety Disorders; Comorbidity; Depressive Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluvoxamine; Humans; Middle Aged; Obsessive-Compulsive Disorder; Panic Disorder; Treatment Outcome

Reboxetine is a potent antidepressant, with efficacy comparable to that of imipramine, desipramine, and fluoxetine, and has improved side-effect profile. The basis of its efficacy and improved tolerability is sought through studies of reboxetine in a number of pharmacological models of depression.. Pharmacological selectivity for uptake systems was defined by uptake and binding assays for the three monoamine uptake sites. Specificity was determined in 39 different receptor and 6 enzyme assays. In vivo selectivity was defined by measurement of neuronal firing rates in the locus coeruleus, dorsal raphe, and substantia nigra. Reserpine-induced blepharospasm and hypothermia, clonidine-induced hypothermia, defined reboxetine's in vivo pharmacology. Reboxetine's antidepressant potential was evaluated behaviorally by the tail-suspension test, forced swimming, and the DRL72 operant responding test.. Reboxetine is a potent, selective, and specific norepinephrine reuptake inhibitor (selective NRI) as determined by both in vitro and in vivo measurements. Unlike desipramine or imipramine, reboxetine has weak affinity (Ki > 1,000 nmol/L)for muscarinic, histaminergic H1, adrenergic alpha1, and dopaminergic D2 receptors. In vivo action of reboxetine is entirely consistent with the pharmacological action of an antidepressant with preferential action at the norepinephrine reuptake site. Reboxetine showed an antidepressant profile in all tests of antidepressant activity used. Significant decreases in immobility were observed in the tail suspension test and behavioral despair test. Increased efficiency in responding was observed in the DRL72 test.. Reboxetine is a potent, selective, and specific noradrenergic reuptake inhibitor. It has a superior pharmacological selectivity to existing tricyclic antidepressants and selective serotonin reuptake inhibitors when tested in a large number of in vitro and in vivo systems. Given the pharmacological profile, reboxetine is expected to be a selective and potent tool for psychopharmacological research. The use of reboxetine in the clinic will also help clarify the role norepinephrine plays in depression.

Topics: Adrenergic Uptake Inhibitors; Animals; Brain Chemistry; Carrier Proteins; Cells, Cultured; Conditioning, Operant; Depressive Disorder; Dogs; Dose-Response Relationship, Drug; Electrophysiology; Fluvoxamine; Male; Mice; Morpholines; Norepinephrine; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reboxetine; Receptors, Adrenergic; Reinforcement Schedule; Selective Serotonin Reuptake Inhibitors; Synaptosomes

The aim of this paper is to report a case of symptomatic methadone toxicity associated with fluvoxamine treatment.. A 28-year-old woman was admitted to hospital with severe hypoxaemia and hypercapnia indicating hypoventilation. Medication prior to admission had been stable and included methadone 70 mg daily and diazepam 2 mg twice daily. Three weeks before admission she had commenced treatment with fluvoxamine.. Methadone was decreased to 50 mg daily and diazepam was tapered to zero.. The serum methadone concentration decreased and oxygenation improved considerably.. Clinicians should be aware of the potential for a significant drug interaction between fluvoxamine and methadone.

Topics: Adult; Antidepressive Agents, Second-Generation; Depressive Disorder; Drug Interactions; Female; Fluvoxamine; Humans; Hypercapnia; Hypoxia; Methadone; Narcotics; Substance-Related Disorders

Topics: Age Factors; Aged; Comorbidity; Depressive Disorder; Female; Fluvoxamine; Humans; Parkinson Disease; Parkinson Disease, Secondary; Selective Serotonin Reuptake Inhibitors

The study was carried out to quantify the excretion of the selective serotonin reuptake inhibitor paroxetine in breast milk.. In 6 lactating women, the concentrations of paroxetine in breast milk and serum were studied at the times for assumed minimum (24 hours after dose intake) and maximum (4-7 hours after dose intake) drug levels in milk. Moreover, a seventh subject was studied with frequent and regular sampling throughout a dose interval of 24 hours at 2 different dose levels.. The mean milk/serum concentration ratios in the first 6 subjects ranged from 0.39 to 1.11 (overall mean +/- SD = 0.69 +/- 0.29), and the mean estimated dose to the infants ranged from 0.7% to 2.9% (overall mean +/- SD = 1.4% +/- 0.79%) of the weight-adjusted maternal dose. Based on area-under-the-curve data from the seventh subject, the milk/serum concentration ratio was 0.69 at a dose of 20 mg/day and 0.72 at a dose of 40 mg/day; the estimated relative doses to the infant were 1.0% and 2.0%, respectively. The mean increase in milk paroxetine concentrations from assumed minimum to assumed maximum was 61% (range, 4%-172%; p < .01). The mean paroxetine concentration in hindmilk was 78% higher than in foremilk (range, 16%-169%; p < .01), an increase that was parallel to the increase in milk triglyceride levels (r = 0.83, p = .005). No adverse drug reactions or unusual behaviors were reported in the infants.. The study indicates that the relative dose to a suckling infant for paroxetine is lower than that reported for fluoxetine and citalopram and higher than that reported for sertraline and fluvoxamine.

Topics: Adult; Breast Feeding; Citalopram; Depressive Disorder; Dose-Response Relationship, Drug; Female; Fluoxetine; Fluvoxamine; Humans; Lactation; Milk, Human; Panic Disorder; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline; Triglycerides

(1) Serotonin reuptake inhibitor antidepressants are not teratogenic in animals. (2) Human data are limited, and most involve fluoxetine. (3) No data pointing to a teratogenic effect after fluoxetine exposure during the first trimester have been reported. (4) Self-resolving neurological signs have been observed in newborns exposed to fluoxetine at the end of pregnancy. (5) The paucity of data requires all prescribers of antidepressants to pregnant women to report any adverse events occurring in a child or mother to a teratogenicity or pharmacovigilance centre.

Topics: Abnormalities, Drug-Induced; Antidepressive Agents, Second-Generation; Child; Child, Preschool; Clinical Trials as Topic; Depressive Disorder; Female; Fluoxetine; Fluvoxamine; Humans; Infant; Infant, Newborn; Paroxetine; Pregnancy; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

Approximately 60% of patients with major depression disorder show a beneficial response to total sleep deprivation (TSD), but the positive effect of TSD is short, and naps or the following night's sleep destroy it. Various methods have been tried to stabilize the positive sleep-deprivation effect. A consecutive 1-week advance in the sleep phase stabilized mood in more than 50% of the sleep-deprivation responders. We examined 40 male patients with major depression who in addition to medical treatment took part in a phase advance study to prove possible synergistic effects. About 60% of the patients showed positive mood stabilization after 1-week of treatment when the patients were sleep-deprivation responders. These results support data from other groups.

Topics: Adult; Circadian Rhythm; Combined Modality Therapy; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Middle Aged; Patient Admission; Personality Inventory; Selective Serotonin Reuptake Inhibitors; Sleep Deprivation; Sleep Stages; Treatment Outcome

Topics: Adult; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Attention Deficit Disorder with Hyperactivity; Clomipramine; Depressive Disorder; Drug Therapy, Combination; Fluvoxamine; Humans; Male; Obsessive-Compulsive Disorder

Topics: Behavior Therapy; Depressive Disorder; Drug Resistance; Fluvoxamine; Humans; Selective Serotonin Reuptake Inhibitors

The relationship between peripheral serotonergic variables, melancholic traits, and clinical improvement after antidepressant treatment was examined in 83 drug-free major depressive patients. Plasma serotonin (5-HT) concentrations was lower in untreated melancholic patients (1.00 +/- 0.11 vs. 1.84 +/- 0.28 ng/mL, p < 0.008; N = 40 and 43, respectively). A tendency was observed for plasma 5-hydroxyindoleacetic acid (p < 0.06), whereas platelet 5-HT and plasma tryptophan did not differ between groups. After blood sampling and clinical ratings, treatment began with fixed doses of 5-HT uptake inhibitors (clomipramine or fluvoxamine), monoamine oxidase inhibitors, or tianeptine, a 5-HT uptake enhancer. There was no significant difference in response rates between patients with and without melancholic traits. The relationship between the clinical response at 6 weeks (>50% reduction of baseline Hamilton score) and the pretreatment values of biochemical variables was examined. Responders had a lower pretreatment platelet 5-HT (530 +/- 36 vs. 664 +/- 50 ng/10(9) platelets, p < 0.03; N = 44 and 39, respectively). Patients with a platelet 5-HT concentration above 800 ng/10(9) platelets had a lower response rate than those below this value (p < 0.003). This difference was maximal in the subgroup of patients treated with 5-HT uptake inhibitors (N = 49). In this subgroup, the response rates of patients with 5-HT concentrations below and above the cutoff point were, respectively, 70% and 17% (p < 0.001). A pretreatment platelet 5-HT value above 800 ng/10(9) platelets had a predictive value for a negative response of 92%. These results suggest the presence of biochemical differences in the peripheral serotonergic system between melancholic and nonmelancholic patients. The inverse relationship between the pretreatment platelet 5-HT content and clinical response may be useful in the investigation of the relationship between the 5-HT system and antidepressant response.

Topics: Adult; Antidepressive Agents; Blood Platelets; Clomipramine; Depressive Disorder; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Middle Aged; Prognosis; Serotonin; Thiazepines; Tryptophan

This prospective study assessed fluvoxamine serum concentrations under two different fixed doses. The study included 15 male and female patients who met the DSM-III-R criteria for major depression. They were prescribed 50 mg fluvoxamine twice a day for 2 weeks and 100 mg twice a day thereafter. Drug monitoring was carried out on days 14 and 28. Fluvoxamine serum concentrations were highly variable between patients. After the dose was doubled, the serum concentrations of fluvoxamine increased disproportionately (mean, 3.4-fold), and there was a significantly (p < 0.05) more pronounced increase in men (4.6-fold) than in women (2.4-fold). These results provide evidence of nonlinear, sex-dependent pharmacokinetics of fluvoxamine.

Topics: Adult; Aged; Aged, 80 and over; Antidepressive Agents, Second-Generation; Depressive Disorder; Dose-Response Relationship, Drug; Female; Fluvoxamine; Humans; Male; Middle Aged; Prospective Studies; Sex Factors

Topics: Aged; Depressive Disorder; Dyskinesia, Drug-Induced; Female; Fluvoxamine; Humans; Neurologic Examination; Selective Serotonin Reuptake Inhibitors

Mood disorders are known to cluster within families, but the mode of transmission remains largely unknown. The purpose of our analysis was to determine whether selection of a sample that was homogeneous in its response to an antidepressant provided stronger evidence for a single major locus. Complex segregation analysis was applied to a sample of 171 Italian families of bipolar and unipolar probands that were responsive to the antidepressant fluvoxamine. We used regressive logistic analyses to determine the best fit from among environmental, arbitrary Mendelian, dominant, recessive and additive models. For the 171 affective families with probands that were responsive to the antidepressant fluvoxamine, a Mendelian model of inheritance was rejected. When considering 68 families of bipolar probands, the best fit was obtained for a Mendelian dominant model of transmission. The identification of a Mendelian mode of transmission in bipolar subjects who were selected according to their response to fluvoxamine supports the use of a pharmacological criterion as a tool for identifying true genetic disorders.

Topics: Adult; Depressive Disorder; Female; Fluvoxamine; Genetics, Population; Humans; Italy; Male; Middle Aged; Phenotype; Selective Serotonin Reuptake Inhibitors

The objective of this study was to examine the cost effectiveness of fluvoxamine compared with tricyclic antidepressants (TCAs) in the treatment of patients with depressive episodes.. A Markov process model was constructed to model the effectiveness, as measured by time without depression, and the costs of both treatments. The model examined a period of 18 months in order to capture the influence of both relapses and recurrences on the outcomes. Data for the construction of the model came from the published literature, an expert panel and a large multicentre randomised clinical trial. Costs were obtained from published sources. The setting for this study was France.. The results of the baseline analysis showed that the use of fluvoxamine in the maintenance treatment (recurrence prevention) of depressive disorders was less costly than TCAs with total costs (direct and indirect costs) of 40,232.40 French francs (FF) and FF52,257.53, respectively (1996 values). In addition, due to the prevention of relapse and recurrence, effectiveness favoured fluvoxamine as it was associated with a longer period of time without depression when compared with TCAs (79% of the study period vs 71%). Sensitivity analyses confirmed the robustness of these findings.. In conclusion, on the basis of the assumptions used in the model, the use of fluvoxamine as maintenance therapy is clinically and economically justified in patients with depressive disorders.

Topics: Antidepressive Agents, Second-Generation; Cost-Benefit Analysis; Depressive Disorder; Fluvoxamine; France; Humans; Markov Chains; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

This study examined, in the largest sample of major depressives reported so far, platelet serotonergic parameters (5-HT uptake, [3H]paroxetine binding and 5-HT2A receptors measured by [3H]LSD binding) in 60 antidepressant-free depressed patients and 40 age- and gender-matched control subjects before treatment, and in 45 major depression patients during treatment with antidepressants. We found that, at baseline, the density (Bmax) of 5-HT2A receptors was significantly higher (by 39%) in depressed patients than in controls. Suicidal patients had significantly higher Bmax values than controls or non-suicidal patients. The rate of serotonin uptake (Vmax), but not the uptake at a single concentration, was significantly higher in depressed patients, particularly in females. There was no significant difference between the Kd or Bmax of [3H]paroxetine binding in control and depressed subjects. Treatment with antidepressant drugs of different pharmacological profile had no significant effect on the density of 5-HT2A receptors, nor did the receptor number predict the response to treatment. The affinity of serotonin uptake site for 5-HT and [3H]paroxetine significantly decreased during treatment with antidepressants, particularly SSRIs. Suppression of 5-HT uptake correlated with decreases in Hamilton depression (HAMD) scores. Our data suggest that the increased density of platelet 5-HT2A receptors may be associated with untreated major depression in antidepressant-free depressed patients, in particular those with suicidal thoughts. The persistence after antidepressant treatment and clinical improvement would suggest that up-regulation of 5-HT2A receptors is a trait rather than state phenomenon. Correlation of 5-HT uptake suppression with decreases in HAMD scores suggests that serotonin uptake inhibition is a relevant factor in antidepressant drug effect and clinical improvement.

Topics: Adolescent; Adult; Aged; Amitriptyline; Antidepressive Agents; Blood Platelets; Carrier Proteins; Depressive Disorder; Doxepin; Female; Fluvoxamine; Follow-Up Studies; Humans; Male; Middle Aged; Personality Inventory; Receptor, Serotonin, 5-HT2A; Receptors, Drug; Receptors, Serotonin; Serotonin; Trazodone; Treatment Outcome

We have studied fasting plasma tryptophan (TRP) levels and tryptophan/large neutral amino acid (TRP/LNAA) ratios in 12 patients with obsessive-compulsive disorder (OCD) and 12 patients with OCD and a coexisting current diagnosis of major depressive disorder (OCD-MDD). Assessments were made at baseline and after 6 weeks of treatment with fluvoxamine. OCD-MDD patients had significantly lower baseline TRP levels and TRP/LNAA ratios than OCD patients. After 6 weeks of fluvoxamine treatment, OCD-MDD patients had significant increases in plasma TRP and TRP/LNAA ratio, whereas OCD patients had non-significant decreases. Our data suggest that a major depressive syndrome could be a state variable affecting the changes in plasma TRP and TRP/LNAA ratio in OCD patients.

Topics: Adult; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Middle Aged; Obsessive-Compulsive Disorder; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Tryptophan

Kleptomania, one of the rare impulse-control disorders, is characterized by an irresistible impulse to steal objects not needed for personal use or monetary value. There is a comorbidity between mood disorders, eating disorders, anxiety disorders, personality disorders, and kleptomania. Several recent case reports have suggested that serotonin reuptake inhibitors could be effective in the treatment of obsessive-compulsive spectrum disorders and specifically in kleptomania. We describe three depressed patients who paradoxically experienced kleptomanic behavior during treatment with serotonin selective reuptake inhibitors.

Topics: Aged; Antidepressive Agents, Second-Generation; Depressive Disorder; Disruptive, Impulse Control, and Conduct Disorders; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Selective Serotonin Reuptake Inhibitors

It has been reported that the 5-HT1A autoreceptor antagonist pindolol can accelerate the antidepressant response to the selective serotonin (5-HT) reuptake inhibitor (SSRI) paroxetine, presumably by preventing the initial decrease in firing activity of 5-HT neurons produced by the SSRI. The present study was aimed at further exploring this treatment strategy in three groups of 10 patients with unipolar major depression allocated sequentially to three treatment arms for 28 days. The administration of the selective 5-HT1A agonist buspirone (20 mg/day for 1 week and 30 mg/day thereafter) with pindolol (2.5 mg TID) was used to activate selectively postsynaptic 5-HT1A receptors. This combination produced a greater than 50% reduction of depressive symptoms in the first week in 8 of 10 patients and the response was sustained for the remainder of the trial. In contrast, the combination of tricyclic antidepressant drugs devoid of effect on the 5-HT reuptake process (desipramine or trimipramine, 75 mg/day for 1 week and 150 mg/day thereafter) with pindolol resulted in only one of ten patients achieving a 50% improvement after 28 days. The combination of the SSRI fluvoxamine (50 mg/day for 1 week and 100 mg/day thereafter) with pindolol produced a marked antidepressant effect but did not act as rapidly as the buspirone plus pindolol combination with none, four, and eight patients achieving a 50% amelioration after 7, 14, and 21 days of treatment, respectively. These results provide further evidence that pindolol may accelerate the antidepressant effect of drugs that alter the function of the 5-HT neurons and that the selective activation of postsynaptic 5-HT1A receptors may induce a rapid and robust antidepressant response.

Topics: Adult; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Buspirone; Depressive Disorder; Desipramine; Drug Synergism; Female; Fluvoxamine; Humans; Male; Pindolol; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Selective Serotonin Reuptake Inhibitors; Serotonin Receptor Agonists; Trimipramine

Many patients with affective illness show partial or otherwise unsatisfactory responses to standard treatments, encouraging trials of combinations of pharmacologically dissimilar antidepressants.. Records of consecutive outpatients with affective disorders only partially responsive to treatment with a serotonin reuptake inhibitor (SRI) or bupropion, alone, were reviewed for changes in specific symptoms and risks of adverse events when an SRI and bupropion were combined.. Greater symptomatic improvement was found in 19 (70%) of 27 subjects during a mean +/- SD of 11 +/- 14 months of combined daily use of bupropion (243 +/- 99 mg) with an SRI (31 +/- 16 mg fluoxetine-equivalents) than with either agent alone. Adverse effect risks were similar to those associated with each monotherapy, with a > 10% incidence of sexual dysfunction (N = 11, 41%), insomnia (N = 6, 22%), anergy (N = 4, 15%), and tremor (N = 3, 11%) during combined therapy; there were no seizures.. With conservative dosing and close monitoring, combinations of SRIs with bupropion in this uncontrolled clinical series appeared to be safe and often more effective than monotherapy.

Topics: 1-Naphthylamine; Adult; Aged; Ambulatory Care; Anxiety Disorders; Bupropion; Depressive Disorder; Drug Administration Schedule; Drug Therapy, Combination; Dysthymic Disorder; Epilepsy; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Panic Disorder; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

Comparative study of the peculiarities of clinical action of fluoxetine and fluvoxamine in 65 patients with endogenous depressions revealed their high efficiency (in 74.3% and 64.3% respectively). Fluoxetine was characterised by predominance of a stimulating effect from the first days of treatment as well as by relatively late manifestation of very thymoleptic and tranquilizing impact (during 3-4 weeks). Fluvoxamin displayed relatively uniform occurrence of separate clinical effects together with predominance and early appearance of antidepressive influence. On the basis of the comparison of the peculiarities of either clinical action of fluoxetine and fluvoxamin or their side effects with those of traditional antidepressive drugs (amitryptilin and ludiomil) the preferable indications for their prescription were determined. Thus fluoxetine was very good in treatment of apathetic-adynamic depressions while fluvoxamin was recommended for therapy of anxious and melancholic depressions. Antidepressants studied were ranked in the following way in terms of decrease of sedative effect and increase of stimulating action: amitryptilin, fluvoxamin, ludiomil, fluoxetine. The proper thymoleptic effect of fluoxetine and fluvoxamin exceeded the same effect of amitryptilin and ludiomil.

Topics: Adolescent; Adult; Amitriptyline; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Depressive Disorder; Drug Evaluation; Female; Fluoxetine; Fluvoxamine; Humans; Male; Maprotiline; Middle Aged; Time Factors

A high degree of comorbidity appears to exist between obsessive-compulsive disorder (OCD) and depression, both with respect to symptomatology and at the syndromal level. It has been argued that nonspecific effects on dysphoric mood, anxiety, and depressive symptoms account for the therapeutic efficacy of antidepressants in OCD. However, several controlled studies have shown that neither the presence nor initial severity of depression has any impact on therapeutic improvement in OCD. In particular, studies with the serotonin selective reuptake inhibitors (SSRIs) fluvoxamine and fluoxetine have revealed beneficial effects in OCD, irrespective of the presence of depressive symptoms. The efficacy of the other SSRIs in OCD requires further study. In conclusion, the improvement in OC symptoms seen with fluvoxamine and fluoxetine does not depend on concomitant affective disorder.

Topics: Comorbidity; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Obsessive-Compulsive Disorder; Selective Serotonin Reuptake Inhibitors

Topics: Adult; Comorbidity; Depressive Disorder; Drug Interactions; Female; Fluvoxamine; Half-Life; Health Care Costs; Humans; Lung Diseases, Obstructive; Theophylline

There was elaborated expert models based on computer data base including 42 formalized signs (anamnesis, state of the patients, medical measures and indices of expert estimation of the response to therapy, based on the reduction of scores of Hamilton's scale). The study was carried out in 104 in-patients whose clinical states corresponded according to ICD-10 to category "depressive episode" and "recurrent depressive disorder". The patients were divided into 2 groups: in the first one the treatment was performed by serotoninergic antidepressants (SA)-fluoxetine (20 patients), fluvoxamine (20), sertraline (30). Tricyclic antidepressant (TAD) amitryptiline was administered to 34 patients of the second group. Two data bases were formed: responders to TAD and responders to SA. Natural pair model of classification (error of the model--12.5%) including 9 informative signs, was constructed, that gave chance to define probability sensitivity to TAD and SA. Check-up of computer model revealed that 3 patients of SA group didn't submit to decisive rule, while there were found 2 such patients in TAD application. Application of computer experiment permitted to turn from group prognosis to individual one.

Topics: 1-Naphthylamine; Amitriptyline; Antidepressive Agents, Tricyclic; Depressive Disorder; Fluoxetine; Fluvoxamine; Follow-Up Studies; Humans; Recurrence; Selective Serotonin Reuptake Inhibitors; Sertraline; Severity of Illness Index; Treatment Outcome

We prolonged from 24 to 36 months a follow-up study of unipolar subjects with a high probability of recurrence treated with fluvoxamine (n = 32) or lithium (n = 32). During the extra observation period, two patients developed mania and were excluded from the study. There were no further recurrences in either the lithium or the fluvoxamine group. In our sample, previous prescriptions of tricyclics seem to predict a worse prognosis.

Topics: Adult; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Antimanic Agents; Bipolar Disorder; Depressive Disorder; Female; Fluvoxamine; Follow-Up Studies; Humans; Lithium; Male; Recurrence; Treatment Outcome

We describe the case of a depressive patient who was a rapid metabolizer of CYP2D6 substrates and a heavy smoker, and who did not respond to several courses of treatment with antidepressants, as a result of unusually low drug-plasma levels. During hospitalization, he did not improve after treatment with clomipramine (150-225 mg/day during three weeks), but showed a response within four days after addition of fluvoxamine (100 mg/day). Plasma levels of clomipramine and desmethylclomipramine changed from 58 ng/ml and 87 ng/ml to 223 ng/ml and 49 ng/ml respectively one week after addition of fluvoxamine. Present knowledge of the role of cytochrome P-450 isozymes, such as CYP1A2, CYP2C19, CYP2D6, and CYP3A4, in the metabolism of psychotropic drugs as well as therapeutic drug-plasma level monitoring may thus help to determine individual treatment.

Topics: Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Clomipramine; Combined Modality Therapy; Cytochrome P-450 CYP2D6; Depressive Disorder; Drug Interactions; Drug Resistance; Electroconvulsive Therapy; Fluvoxamine; Humans; Male; Middle Aged; Phenotype; Psychiatric Status Rating Scales; Smoking

Topics: Adult; Antidepressive Agents, Second-Generation; Depressive Disorder; Drug Overdose; Female; Fluvoxamine; Humans; Suicide, Attempted; Trimeprazine

Topics: Adult; Antidepressive Agents, Second-Generation; Depressive Disorder; Female; Fingers; Fluvoxamine; Humans; Infarction; Raynaud Disease; Selective Serotonin Reuptake Inhibitors

Topics: Adult; Comorbidity; Depressive Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluvoxamine; Half-Life; Humans; Obsessive-Compulsive Disorder; Orgasm; Sexual Dysfunctions, Psychological

Topics: Amino Acids; Antidepressive Agents; Biomarkers; Citalopram; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Predictive Value of Tests; Selective Serotonin Reuptake Inhibitors; Tryptophan

A qualitative analysis of studies on the efficacy and side-effects of selective serotonin reuptake inhibitors (SSRIs) for the treatment of elderly people with depression is presented. Only placebo-controlled or comparison studies of SSRI versus other antidepressants were included. The description and methodological quality of the analysed studies were important criteria in the outcome of the analysis. Quality was assessed by means of a blinded review approach. After excluding duplicate publications, 16 studies were analysed, of which six turned out to be of good quality. The results indicated that at the end of the treatment periods (4-8 weeks) all antidepressants were equally effective. Side-effects occurred less frequently with SSRIs than with tricyclics (TCAs), and different side-effect profiles were found. Significantly fewer SSRI-treated patients than TCA-treated patients dropped out both overall and due to side-effects.

Topics: 1-Naphthylamine; Aged; Anorexia; Antidepressive Agents; Depressive Disorder; Diarrhea; Fluoxetine; Fluvoxamine; Humans; Meta-Analysis as Topic; Nausea; Paroxetine; Patient Dropouts; Selective Serotonin Reuptake Inhibitors; Sertraline; Single-Blind Method

Concentrations of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) were similar in patients with major depressive disorder and in those with non-depressive psychiatric problems, although concentrations were significantly lower in suicidal patients (particularly in those attempters who used violent methods) than in non-suicidal patients. In contrast, post mortem CSF 5-HIAA concentrations in suicide victims were significantly higher than in controls. In addition, there appear to be fewer imipramine binding sites in the left frontal cortex of the brain than the right in suicide victims, the converse being true for controls. The serotonergic dysfunction associated with suicidal behaviour is likely to be involved in other conditions such as depression, schizophrenia and anxiety disorder. Thus selective serotonin reuptake inhibitors may be useful in the treatment of various types of psychiatric disease. Fluvoxamine, in particular, is associated with a very low incidence of suicidality compared with other antidepressants.

Topics: Binding Sites; Depressive Disorder; Fluvoxamine; Frontal Lobe; Humans; Hydroxyindoleacetic Acid; Imipramine; Selective Serotonin Reuptake Inhibitors; Suicide; Suicide, Attempted

The serotonin reuptake inhibitors (SSRIs) are generally better tolerated than the traditional tricyclic antidepressants (TCAs) in the treatment of major depression. In particular the SSRIs are relatively free from cognitive and psychomotor effects likely to cause behavioural toxicity. Behavioural toxicity is studied using a battery of psychometric assessments. This paper discusses the effects of the TCAs and SSRIs on two such assessments, choice reaction time (CRT) and critical flicker fusion threshold (CFFT). CRT measures psychomotor speed, and CFFT assesses the information processing capacity of the CNS. The behavioural toxicity associated with the traditional TCAs can lead to an increased accident risk, whereas the SSRIs are not associated with such effects. Clinically relevant differences in the behavioural toxicity of the SSRIs are highlighted.

Topics: Accidents, Traffic; Antidepressive Agents, Tricyclic; Automobile Driving; Cognition Disorders; Depressive Disorder; Dothiepin; Flicker Fusion; Fluvoxamine; Humans; Psychomotor Performance; Reaction Time; Selective Serotonin Reuptake Inhibitors; Time Factors

Topics: Adult; Brain; Depressive Disorder; Female; Fluvoxamine; Humans; Killer Cells, Natural; Male; Middle Aged; Personality Assessment; Serotonin

Topics: Depressive Disorder; Dose-Response Relationship, Drug; Female; Fluvoxamine; Humans; Lupus Erythematosus, Cutaneous; Middle Aged; Myoclonus

Topics: Adult; Depressive Disorder; Dystonia; Female; Fluvoxamine; Humans; Mandibular Diseases; Neurologic Examination; Selective Serotonin Reuptake Inhibitors

Topics: Depressive Disorder; Fluoxetine; Fluvoxamine; Humans

Topics: Cyproheptadine; Depressive Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluvoxamine; Humans; Male; Middle Aged; Orgasm; Patient Compliance; Recurrence

Prescription-event monitoring (PEM) is one of two national systems of drug safety monitoring practised in Britain. The objective of this PEM study was to assess the safety of fluvoxamine and to monitor the occurrence of untoward and other events during treatment. A total of 10,401 patients treated with the drug in general practices throughout England were studied and data were analysed in the Drug Safety Research Unit, Southampton. The main outcome measures were the overall incidence of events per 1000 patients; the incidence during the first month of treatment; the mean incidence for months 2-6 of treatment; and the ratio of these rates as a signal that an event could be drug related. The most commonly reported category of events was neuropsychiatric while the most commonly reported individual events were nausea and vomiting. Fluvoxamine was shown to be a safe drug and no unexpected or previously undetected drug-related events were encountered. There was a relatively high incidence of gastro-intestinal symptoms, but other adverse reactions often encountered during treatment with tricyclic antidepressants were not frequently reported.

Topics: Adolescent; Adult; Aged; Anxiety Disorders; Depressive Disorder; Drug Monitoring; Drug Prescriptions; Drug Therapy, Combination; England; Family Practice; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Pregnancy; Product Surveillance, Postmarketing; Sex Factors

Topics: Bradycardia; Buspirone; Depressive Disorder; Drug Interactions; Drug Overdose; Electrocardiography; Female; Fluvoxamine; Humans; Middle Aged; Suicide, Attempted

We report five cases where fluvoxamine (FLVX) was added to maintenance treatment with methadone (MTD) in addict patients with affective disorders. In view of the implication of FLVX in several metabolic drug interactions, MTD plasma levels were measured before and after treatment with FLVX. A slight increase (approximately 20% of the MTD plasma level/dose ratio) occurred in two cases. In the remaining three patients, the interaction was more pronounced (40-100% increase of the MTD plasma level/dose ratio), with clinical manifestations of opiate withdrawal after stopping FLVX therapy in one case. Caution is needed when starting or stopping treatment with FLVX in patients receiving maintenance treatment with methadone.

Topics: Adult; Depressive Disorder; Drug Interactions; Female; Fluvoxamine; Humans; Male; Methadone; Opioid-Related Disorders

A depressive patient, a non-responder to trimipramine (TRI), was comedicated first with citalopram (CIT) and then with fluvoxamine (FLUV). Both the TRI-CIT and TRI-FLUV combination treatments led to a worsening of the depressive state and to the appearance of panic attacks. The addition of FLUV to TRI resulted in a twofold increase of the plasma levels of TRI and to a slight increase of its N-demethylated and 2-hydroxylated metabolites. These results suggest that the interaction between FLUV and TRI occurred at the level of cytochrome P-450IID6 and cytochrome P-450meph in this patient, phenotyped as an extensive metabolizer of both dextromethorphan and mephenytoin. The adverse effects were possibly due to (a) a pharmacokinetic interaction between CIT and FLUV with TRI and/or (b) alterations in serotonergic and/or dopaminergic neurotransmission.

Topics: Aged; Citalopram; Depressive Disorder; Dextromethorphan; Drug Interactions; Female; Fluvoxamine; Humans; Mephenytoin; Phenotype; Trimipramine

The effect of fluvoxamine maleate, 100 mg/day for 10 days, on plasma concentrations of tricyclic antidepressants was studied in 15 depressed patients on maintenance therapy with imipramine (7 pts.) or desipramine (8 pts.). In the subgroup treated with imipramine, plasma levels of imipramine increased significantly (p < 0.001) during fluvoxamine coadministration, while levels of desipramine were not modified. Addition of fluvoxamine to patients on a stable desipramine dosage regimen resulted in a slight, but statistically not significant, increase in desipramine plasma concentrations. These results suggest that fluvoxamine is a potent inhibitor of imipramine demethylation, while it has a weak effect on the hydroxylation of desipramine.

Topics: Adult; Depressive Disorder; Desipramine; Drug Interactions; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged

Topics: Adult; Depressive Disorder; Dyskinesia, Drug-Induced; Female; Fluvoxamine; Humans; Neurologic Examination; Tongue Habits

Selective serotonin reuptake inhibitors (SSRI) have been established as effective drugs in the treatment of depressive and anxiety disorders. However, there are also reports that they can induce depressive symptoms and suicidal thoughts in patients. Eighty of 230 patients who met the DSM-III-R criteria for panic disorder received, during the course of treatment, fluvoxamine (a selective serotonin reuptake inhibitor) at a dose level between 50-200 mg/day. The patients were clinically evaluated for a history of affective disorder and for the presence of affective symptoms before the treatment and for emergence of depressive symptoms during the treatment. Seven of the 80 patients (9%) developed symptoms of depression despite a good antianxiety response. Five of the 7 patients received fluvoxamine as second choice after tricyclic antidepressants (TCA). These patients had no history of affective disorder, and no symptoms of depression were present before the treatment with fluvoxamine. The depressive symptoms abated after the fluvoxamine was discontinued and TCA or clonazepam was prescribed. The depressive symptoms reappeared when fluoxetine was administered. None of these 7 patients developed depressive symptoms while treated with TCA or clonazepam. Among the 150 patients treated with TCA and benzodiazepines, not a single case of depression was seen in patients without a previous history of depression. These results suggest a vulnerability among some of panic disorder patients to noradrenergic-serotonergic imbalance caused by SSRI, which has to be taken into clinical consideration.

Topics: Adult; Depressive Disorder; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Panic Disorder; Suicide

To report cases of manic-like behavior induced by fluvoxamine, a selective serotonin-reuptake inhibitor; to review pertinent literature; and to encourage replication of our findings in larger patient samples.. Description of a case series of fluvoxamine-induced, manic-like behavior.. Eight patients with depression or obsessive features who developed manic-like behavior after initiation of fluvoxamine therapy.. Manic symptomatology resolved in all eight patients following dosage reduction or withdrawal of fluvoxamine. Four patients still are maintained on low-dose fluvoxamine without recurrent manic symptoms.. Our case series suggests that fluvoxamine may have the ability to induce or unmask manic behavior in depressed patients. Clinicians are alerted to monitor for this "switching" effect, especially in patients previously or currently treated with neuroleptics or lithium, and in those patients exhibiting characteristics of obsessive-compulsive disorder.

Topics: Adult; Bipolar Disorder; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Middle Aged

Topics: Adult; Antisocial Personality Disorder; Depressive Disorder; Dose-Response Relationship, Drug; Fluoxetine; Fluvoxamine; Humans; Impulsive Behavior; Male; Risk Factors; Selective Serotonin Reuptake Inhibitors

Topics: Adult; Depressive Disorder; Drinking; Female; Fluvoxamine; Humans

Topics: Adult; Depressive Disorder; Drug Interactions; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Imipramine; Male; Parasympathetic Nervous System; Stimulation, Chemical

Three cases of blood-letting in association with bulimia nervosa are reported. This association has not previously been described.

Topics: Adult; Bloodletting; Bulimia; Child of Impaired Parents; Combined Modality Therapy; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans; Personality Development; Phenelzine; Phototherapy; Psychotherapy; Psychotherapy, Group; Students, Medical

We evaluated patients abruptly withdrawn from fluvoxamine, a serotonin selective reuptake inhibitor, for evidence of a discontinuation syndrome.. In an open-label study, 14 subjects were abruptly withdrawn from fluvoxamine after treatment lasting 8 months (7 months for 1 patient). Psychological, somatic, and perceptual symptoms were assessed at Day 5, Day 10, and Day 14 postdiscontinuation. Anxiety and depression were assessed using clinician and self-rated scales.. Twelve (86%) of 14 subjects developed new symptoms. The most frequent symptoms reported were dizziness/incoordination, headaches, nausea, and irritability. Symptoms peaked on Day 5 postdiscontinuation. Only 1 subject had a recurrence of panic, but another developed anxiety and depression; both were remedicated.. Abrupt fluvoxamine discontinuation is associated with a characteristic syndrome in many patients.

Topics: Adult; Anxiety Disorders; Depressive Disorder; Dizziness; Female; Fluvoxamine; Follow-Up Studies; Humans; Male; Panic Disorder; Psychiatric Status Rating Scales; Recurrence; Severity of Illness Index; Substance Withdrawal Syndrome; Syndrome

Topics: Adult; Bipolar Disorder; Depressive Disorder; Dose-Response Relationship, Drug; Female; Fluvoxamine; Humans; Male; Middle Aged; Patient Compliance; Platelet Count; Serotonin

The effects of the treatment with fluvoxamine (FVX) on platelet and plasma serotonin (5-HT) have been examined in eleven drug-free major depressive patients. Acute FVX was without effect, whereas the repeated oral treatment (100-150 mg daily, 12 weeks) reduced platelet 5-HT (-89%, P less than 0.001) and plasma 5-HT (-60%, P less than 0.02). Patients who responded to the treatment at 6 weeks (Hamilton score less than or equal to 10) had significantly lower (-39%, P less than 0.02) pretreatment values of platelet 5-HT than the rest. This suggests that 'low 5-HT' patients may have a more rapid improvement after fluvoxamine. Platelet 5-HT and HDRS correlated significantly along the treatment (r = 0.679, P less than 0.01). These data demonstrate a marked action of fluvoxamine as 5-HT uptake inhibitor at therapeutic doses and confirm that this mechanism is relevant for its efficacy as antidepressant drug.

Topics: Adult; Blood Platelets; Depressive Disorder; Extracellular Space; Female; Fluvoxamine; Humans; Hydroxyindoleacetic Acid; Male; Middle Aged; Selective Serotonin Reuptake Inhibitors; Serotonin

A 55-year-old man presented with a 5-year history of Parkinson's disease and a 6-month history of major depression. The patient's depressive symptoms responded to treatment with fluvoxamine, a selective and potent serotonin reuptake inhibitor. Tryptophan depletion testing, which acutely lowers central serotonin levels, caused a brief exacerbation of the depressive illness, which resolved upon tryptophan repletion. Serotonergic dysfunction may be an etiologic factor in depression that occurs in Parkinson's disease.

Topics: Depressive Disorder; Fluvoxamine; Humans; Male; Middle Aged; Neurotransmitter Uptake Inhibitors; Parkinson Disease; Serotonin; Tryptophan

Topics: Depressive Disorder; Female; Fluvoxamine; Humans; Middle Aged; Schizophrenia

We describe four patients in whom the addition of fluvoxamine (100 mg/day) to the treatment with imipramine or desipramine (100-150 mg/day) resulted in a dramatic increase in the plasma concentrations of the tricyclic antidepressants associated with adverse effects. These observations indicate that fluvoxamine inhibits both the demethylation of imipramine and, possibly to a lesser extent, the hydroxylation of desipramine. The combination of fluvoxamine with tricyclic antidepressants should be avoided whenever possible.

Topics: Depressive Disorder; Desipramine; Drug Interactions; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged

Fluvoxamine was administered in an open trial of 50 hospitalized patients with major depression of the melancholic type (DSM-III-R) for an average period of 24.56 days in mean minimal and maximal daily doses of 100-311 mg orally after a wash-out interval of 1-14 days. Treatment achieved complete improvement in 54% and partial improvement in 16% of the patients, significantly more frequently in women than in men. The antidepressant effect of fluvoxamine was confirmed also by a statistically significant reduction of the global HAMD and FKD score, starting on the 7th day of the trial. The therapeutic effect was clinically apparent during the second week of treatment. The best therapeutic effect was achieved in anxiety depressions (65%), to a lesser degree inhibitory depressions (50%) and atypical ones (46%), as apparent from the value of Náhunek's antidepressive index 0.88 which suggests a significant anxiolytic effectiveness of fluvoxamine. Fluvoxamine had a positive effect on the majority of HAMD and FKD items, incl. a depressive mood, anxiety, feelings of guilt, anhedonia, reduced interest and ability, obsession, depressive thoughts and suicidal tendencies. Reduced motor activity, loss of appetite, insight, somatic symptoms, paranoidity and hypochondria were less influenced. At the onset of treatment the preparation did not reduced insomnia and thus in 72% patients hypnotics were added. In the course of fluvoxamine therapy no suicidal attempts were observed although 34 (68%) of the patients initially admitted had suicidal thoughts. Fluvoxamine is well tolerated by patients; as to side-effects gastrointestinal complaints were most frequent (in 28% of the patients).

Topics: Adult; Aged; Antidepressive Agents; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Middle Aged

Two cases of alopecia observed during treatment with lithium and valproate are described, and the recent literature on this subject is reviewed. Our clinical observations confirm earlier reports. These toxic alopecias are characterized by a diffuse but rarely total hair loss. After stopping medication, the hair grows back generally and completely. Two cases of toxic alopecia are presented where hair grew back following a substitution of lithium by valproate in the first case and after stopping valproate in the second. The evaluation and therapeutic attitude in the presence of alopecia in patients needing mood stabilizers are also discussed.

Topics: Adult; Alopecia; Carbamazepine; Clorazepate Dipotassium; Depressive Disorder; Female; Fluvoxamine; Haloperidol; Hospitalization; Humans; Lithium Carbonate; Methotrimeprazine; Middle Aged; Schizophrenia; Valproic Acid

Topics: Biotransformation; Chromatography, High Pressure Liquid; Depressive Disorder; Fluoxetine; Fluvoxamine; Humans

Topics: Aged; Aged, 80 and over; Depressive Disorder; Drug Therapy, Combination; Female; Fluoxetine; Fluvoxamine; Humans; Valproic Acid

Topics: Aged; Basal Ganglia Diseases; Depressive Disorder; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Fluvoxamine; Humans; Neurologic Examination

Topics: Adult; Depressive Disorder; Fluvoxamine; Genital Diseases, Male; Humans; Male; Middle Aged; Pain; Prospective Studies; Psychiatric Status Rating Scales; Serotonin

Topics: Antidepressive Agents; Depressive Disorder; Fluvoxamine; Humans; Oximes

Topics: Adult; Antidepressive Agents; Bipolar Disorder; Depressive Disorder; Drug Interactions; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Lithium; Male; Oximes

Topics: Antidepressive Agents; Depressive Disorder; Fluvoxamine; Humans; Serotonin Antagonists

Specific inhibitors of 5-HT reuptake are reported to have lower proconvulsive activity than other antidepressants. A patient with post-traumatic epilepsy who had remained fit-free for many years until she was given the 5-HT reuptake inhibitor fluvoxamine is reported. Changes in serotonergic function may play a more widespread role in the pathophysiology of seizure disorders than hitherto thought.

Topics: Brain; Depressive Disorder; Electroencephalography; Epilepsy, Generalized; Epilepsy, Post-Traumatic; Female; Fluvoxamine; Humans; Middle Aged; Myoclonus; Receptors, Serotonin

Topics: Antidepressive Agents; Depressive Disorder; Fluvoxamine; Humans; Oximes; Seizures; Serotonin Antagonists

Whole blood serotonin (5-hydroxytryptamine, 5-HT) was assayed, and factors possibly influencing 5-HT content were investigated in healthy controls. No significant circadian rhythm or effect of dexamethasone or meals was observed. After use of fluvoxamine, a specific 5-HT reuptake inhibitor, the whole-blood 5-HT concentration of patients was strongly reduced. After treatment with tranylcypromine, an unspecific monoamine oxidase inhibitor (MAOI), the 5-HT content was increased. Determination of whole blood 5-HT in patients treated with fluvoxamine presents a measure of drug compliance. Furthermore, the method may have clinical potential for finding an adequate dose when a 5-HT reuptake inhibitor or an MAOI is used.

Topics: Adult; Circadian Rhythm; Depressive Disorder; Dexamethasone; Fluvoxamine; Humans; Male; Oximes; Serotonin; Tranylcypromine

Apathy, indifference, loss of initiative, or disinhibition (without concurrent sedation or hypomania) were observed among five patients receiving the serotonin reuptake blocking antidepressants fluvoxamine or fluoxetine. These effects appeared to be dose related. They disappeared rapidly when the dose of fluvoxamine, which has a short half-life, was reduced. Fluoxetine, which has a long half-life, was more difficult to titrate. A possible relationship between mild drug-induced indifference and the therapeutic effects of serotonin reuptake blocking medication in anxiety disorders is discussed.

Topics: Adult; Agoraphobia; Antidepressive Agents; Anxiety Disorders; Arousal; Depressive Disorder; Dose-Response Relationship, Drug; Fatigue; Female; Fluoxetine; Fluvoxamine; Humans; Impulsive Behavior; Male; Middle Aged; Motivation; Oximes; Panic; Serotonin Antagonists

In the treatment of depression, when antidepressant drug choice is made according to alterations of erythrocyte membrane transport of L-tyrosine and L-tryptophan in the individual patient, the clinical results are superior to those obtained when drugs are prescribed according to the physician's judgment. This is demonstrated by comparing three experimental groups: I, 100 patients treated in relation to their L-tyrosine and L-tryptophan transport; II, 30 patients treated according to the clinician's experience; III, 38 subjects treated against the L-tyrosine and L-tryptophan transport indications. In these groups, the frequency of patients improved by more than 70% is 77%, 47%, and 16%, respectively.

Topics: Adult; Aged; Antidepressive Agents; Depressive Disorder; Erythrocyte Membrane; Female; Fluvoxamine; Humans; Imipramine; Male; Mianserin; Middle Aged; Monoamine Oxidase Inhibitors; Oximes; Piperidines; Receptors, Adrenergic; Receptors, Serotonin; Tryptophan; Tyrosine

The development design and reliability of the Yale-Brown Obsessive Compulsive Scale have been described elsewhere. We focused on the validity of the Yale-Brown Scale and its sensitivity to change. Convergent and discriminant validity were examined in baseline ratings from three cohorts of patients with obsessive-compulsive disorder (N = 81). The total Yale-Brown Scale score was significantly correlated with two of three independent measures of obsessive-compulsive disorder and weakly correlated with measures of depression and of anxiety in patients with obsessive-compulsive disorder with minimal secondary depressive symptoms. Results from a previously reported placebo-controlled trial of fluvoxamine in 42 patients with obsessive-compulsive disorder showed that the Yale-Brown Scale was sensitive to drug-induced changes and that reductions in Yale-Brown Scale scores specifically reflected improvement in obsessive-compulsive disorder symptoms. Together, these studies indicate that the 10-item Yale-Brown Scale is a reliable and valid instrument for assessing obsessive-compulsive disorder symptom severity and that it is suitable as an outcome measure in drug trials of obsessive-compulsive disorder.

Topics: Adult; Ambulatory Care; Antidepressive Agents; Anxiety Disorders; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Obsessive-Compulsive Disorder; Oximes; Psychiatric Status Rating Scales; Psychometrics; Sensitivity and Specificity; Severity of Illness Index

The erythrocyte membrane transport (MT) of L-tyrosine (TYR) and L-tryptophan (TRP) and their plasma concentration showed abnormal mean values in 37 depressed patients compared to control subjects before treatment. The pattern of these abnormal values differed according to the clinical subgroup (DSM III criteria). In bipolar disorders the TYR values were all low and the TRP values showed little change, except a low level of plasma TRP. In major depression, MT were abnormal (MT TYR low, MT TRP high) with a very low plasma TRP. In dysthymic disorders the TYR and TRP values were normal. The normalization of the above biochemical variables was significantly correlated with the clinical improvement; however, the plasma concentration of TRP remained abnormal in some patients who had recovered. In contrast, only plasma TYR and TRP were significantly increased in patients without recovery.

Topics: Adult; Aged; Antidepressive Agents; Bipolar Disorder; Depressive Disorder; Desipramine; Erythrocyte Membrane; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Oximes; Psychological Tests; Tryptophan; Tyrosine

Topics: Depressive Disorder; Energy Metabolism; Female; Fluvoxamine; Humans; Middle Aged; Oximes; Weight Loss

Topics: Adult; Aged; Antidepressive Agents; Depressive Disorder; Dexamethasone; Female; Fluvoxamine; Humans; Male; Melatonin; Middle Aged; Oximes

A total of 6258 patients seen in general practice complaining of low mood with or without associated somatic symptoms was studied. The mean patient entry score on the Montgomery-Asberg Depression Rating Scale (MADRS) was 29.69 (moderately severe depressive disorder). Three-quarters (73%) of the patients were female, average age was 46.1 years, and a reactive element was considered to be present in 43%. Patients received fluvoxamine, a novel anti-depressant, over a treatment period of 6 weeks, dosage starting at either 50 or 100 mg at night increasing after the first week, if necessary, to a maximum of 300 mg per day. Results were analyzed for 5625 patients. Efficacy of treatment was assessed using the MADRS, Psychosomatic Symptom Scale and Clinical Global Impression scales. During treatment, there was a marked improvement in mood and a parallel improvement in somatic symptoms; there was no difference in overall response between those with or without somatic symptoms. By Week 6, patients had improved by approximately 65%, with suicidal ideation being most marked at 81%. Patient compliance was good, the most commonly reported unwanted effect being nausea. In overdoses up to 2 g fluvoxamine no lasting toxic effects were observed. In an 'elderly' sub-group of 1096 patients aged 60 years and over, efficacy and the incidence of unwanted effects were similar, but the drop-out rate due to intolerance was greater than in the younger age sub-group.

Topics: Adult; Aged; Aged, 80 and over; Antidepressive Agents; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Middle Aged; Oximes

This was a 1-year study of fluvoxamine in 31 depressed male and female patients with a history of chronic recurring depression of various types. Fluvoxamine has a rapid action with lifting of the mood often within 4-7 days, in a dosage range from 150 to 200 mg/day. Suicidal ideation in 8 patients disappeared within 5-6 days. There were few side effects. This new antidepressant seemed to be very effective especially in endogenous depression.

Topics: Adult; Aged; Antidepressive Agents; Depressive Disorder; Female; Fluvoxamine; Humans; Male; Middle Aged; Oximes; Psychiatric Status Rating Scales; Recurrence