fluvoxamine and Mood-Disorders

Although the selective serotonin reuptake inhibitor (SSRI) class of antidepressants shares a common primary pharmacology, namely the inhibition of serotonin reuptake, their secondary pharmacology is remarkably heterogeneous. Inhibition of serotonin reuptake and the consequent increase in serotonin availability are responsible for the relief of depressive symptoms and for some of the adverse effects of this class of drugs. Transsynaptic effects such as modulation of signalling cascades, gene expression processes and neuroplasticity are also important in the mechanism of action of antidepressants. However, this review shows that secondary properties of the SSRIs may contribute to the differences in efficacy and tolerability between members of the class. For example, fluvoxamine has affinity for sigma(1)-receptors -- a property likely to be responsible for its particular efficacy in delusional depression. By understanding the properties of SSRIs and employing careful selection of agents for individual patients, physicians are more able to tailor antidepressant treatments to their patients' particular circumstances.

Topics: Antidepressive Agents, Second-Generation; Citalopram; Fluoxetine; Fluvoxamine; Humans; Mood Disorders; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline

Pathological gambling is a disabling disorder that affects at least 2 1/2 million Americans and their families. Although pathological gambling has been characterized as an impulse control disorder, it has also been associated with compulsivity. Essential features of pathological gambling include constantly recurring gambling behavior that is maladaptive, in that personal, familial, and/or vocational endeavors are disrupted. Affective disorders and substance abuse often co-occur. Incidence of suicidality is extremely high. Despite the fact that this disorder is a widespread public health problem, few controlled studies of causes or treatment have been conducted. Preliminary neurobiological studies implicate serotonergic dysfunction in pathological gamblers. Treatment with serotonin reuptake inhibitors, such as clomipramine and fluvoxamine, may be effective in treating this disorder. Well-defined and controlled clinical trials in large samples of pathological gamblers are needed.

Topics: Adolescent; Adult; Comorbidity; Compulsive Behavior; Disruptive, Impulse Control, and Conduct Disorders; Female; Fluvoxamine; Gambling; Humans; Lithium Carbonate; Male; Middle Aged; Mood Disorders; Obsessive-Compulsive Disorder; Placebo Effect; Psychotherapy; Selective Serotonin Reuptake Inhibitors; Self-Help Groups; Serotonin; Substance-Related Disorders; Treatment Outcome

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

Sudden gains are robust predictors of outcome in psychotherapy. However, previous attempts at predicting sudden gains have yielded inconclusive findings. The aim of the present study was to examine a novel, transdiagnostic, transtherapeutic predictor of sudden gains that would replicate in different settings and populations. Specifically, we examined intraindividual variability in symptoms.. We examined data from a randomized controlled trial (RCT) of prolonged exposure therapy for posttraumatic stress disorder (PTSD) in children and adolescents (n = 63), an RCT of cognitive and behavioral therapies for obsessive-compulsive disorder (OCD) in adults (n = 91), and psychodynamic therapy delivered under routine clinical conditions in a naturalistic setting for diverse disorders (n = 106). In all 3 data sets, we examined whether a measure of variability in symptoms occurring during the first sessions could predict sudden gains.. Variability in symptoms was found to be independent of total change during treatment. Variability in symptoms significantly predicted sudden gains in all 3 data sets and correctly classified 81.0%, 69.2%, and 76.9% of individuals to sudden gain or nonsudden gain status, respectively.. The present study represents the first examination of variability in symptoms as a predictor of sudden gains. Findings indicated that sudden gains are significantly predicted by intraindividual variability in symptoms, in diverse settings, contexts, and populations. Advantages of this predictor, as well as clinical and research implications are discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Topics: Adaptation, Psychological; Adolescent; Adult; Child; Cognitive Behavioral Therapy; Combined Modality Therapy; Female; Fluvoxamine; Humans; Implosive Therapy; Individuality; Male; Middle Aged; Mood Disorders; Obsessive-Compulsive Disorder; Psychotherapy, Psychodynamic; Stress Disorders, Post-Traumatic; Treatment Outcome; Young Adult

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

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

Sleep disturbances are commonly observed in mood disorders, and sleep manipulations can influence the clinical status. In the present study, we investigated the possible effect of the 3111 T/C circadian locomotor output cycles kaput (CLOCK) gene polymorphism on insomnia symptomatology during antidepressant treatment. One hundred seventy-eight inpatients were treated with fluvoxamine 300 mg/day (n = 147) or paroxetine 20-40 mg/day (n = 31), 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 (HAM-D). We observed a significantly higher presence of insomnia throughout the trial in homozygotes for the C variant (P = 0.026). Other demographic and clinical features were found not to be related with CLOCK polymorphisms. Overall, our findings may suggest that CLOCK genotype influences the time course of insomnia during antidepressant treatment. This, together with previous findings on this polymorphism could lead to a further dissection of the complexity of mood disorders.

Topics: Adult; Aged; Antidepressive Agents; CLOCK Proteins; Double-Blind Method; Drug Therapy, Combination; Female; Fluvoxamine; Gene Frequency; Genotype; Humans; Male; Middle Aged; Mood Disorders; Multivariate Analysis; Paroxetine; Pindolol; Polymorphism, Genetic; Serotonin Antagonists; Sleep Initiation and Maintenance Disorders; Time Factors; Trans-Activators; Treatment Outcome

We reported an independent association of the short variant of the serotonin transporter gene-linked polymorphic region (SERTPR) and tryptophan hydroxylase (TPH) genes with antidepressant response to selective serotonin reuptake inhibitors (SSRIs). The aim of the present study was to confirm the effect of the SERTPR and TPH gene variants on the SSRIs antidepressant activity in a new sample of major and bipolar depressives. Two hundred and twenty one inpatients (major depressives = 128, bipolar disorder = 93) were treated with SSRIs (fluvoxamine or paroxetine) for 6 weeks; the severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression (HAMD). SERTPR and TPH variants were determined using PCR-based techniques, 220 subjects genotyped for SERTPR and 221 for TPH that were never included in previous studies. SERTPR*s/s variant association with a poor response to SSRI treatment was confirmed, even if with less significant P values (P = 0.034), independently from clinical variables; pooling the present sample with previous ones we observed a highly significant effect (P < 0.000001). TPH*A/A variants showed higher HAMD scores throughout the trial but with only a trend in the same direction of our previous study in terms of a worse response of A/A genotypes. Thus, the previous positive association was not fully replicated for TPH. The present independent replication confirms SERTPR variants as a liability factor for antidepressant efficacy while the TPH effect is not unequivocal.

Topics: Adult; Analysis of Variance; Chi-Square Distribution; DNA; Double-Blind Method; Drug Therapy, Combination; Female; Fluvoxamine; Gene Frequency; Genotype; Humans; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Mood Disorders; Nerve Tissue Proteins; Paroxetine; Polymorphism, Genetic; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins; Treatment Outcome; Tryptophan Hydroxylase

Several studies have demonstrated the involvement of 5-HT1A receptors in the pathogenesis of depression and in the antidepressant response to SSRIs. A functional new variant in the promoter region of the 5-HT1A gene was recently reported (-1019 C>G). The aim of this study is to investigate a possible association between this 5-HT1A receptor variant and antidepressant response to fluvoxamine in a sample of 262 mood-disorder subjects (151 major depressed and 111 bipolars) treated with fluvoxamine for 6 wk. The severity of depressive symptoms was assessed weekly with the Hamilton Rating Scale for Depression (HAMD). 5-HT1A variants did not influence antidepressant response in the whole sample and in unipolar subjects. In bipolars, 5-HT1A*C/C genotype carriers showed a better response to fluvoxamine (p=0.036), independently from clinical variables. The 5-HT1A polymorphism effect on antidepressant response was independent from the previously reported effect of the 5-HTTLPR polymorphism. In conclusion, 5-HT1A variants could influence the antidepressant efficacy in bipolar subjects, even if results must be verified on larger samples.

Topics: Antidepressive Agents, Second-Generation; DNA; Female; Fluvoxamine; Genotype; Humans; Male; Middle Aged; Mood Disorders; Promoter Regions, Genetic; Psychiatric Status Rating Scales; Receptor, Serotonin, 5-HT1A

Co-morbidity of mood and anxiety disorders is often ignored in pharmacotreatment outcome studies and this complicates the interpretation of treatment response. The clinical trials are usually based on single categories from the Diagnostic and Statistical Manual of Mental Disorders (DSM).. The present study is a first attempt to differentiate the responses to antidepressants using a design that differs from that used in previous clinical trials. To avoid bias due to co-morbidity, we included patients with any DSM-III-R diagnosis of mood or anxiety disorder for which antidepressant treatment was indicated. We also explored the role of the diagnosis at the first episode in the efficacy of the different antidepressants.. A total of 92 outpatients with a mood and/or anxiety disorder were randomly assigned to treatment with imipramine or fluvoxamine in a 6-week study. The diagnosis at the first episode--or primary diagnosis--was available for 78 patients, 40 with a primary depression and 38 with a primary anxiety disorder.. Analyses using the MIXED procedure for repeated measures showed no general differences between treatment with imipramine and treatment with fluvoxamine. When the primary diagnoses were taken into consideration, differentiation occurred. Patients with primary depression showed better responses to imipramine than to fluvoxamine. The assumption that patients with primary anxiety disorder would respond better to fluvoxamine than imipramine was observed for only the Clinical Global Impression.. The results suggest that the nature of the first illness episode may be more valuable than the DSM categories of mood or anxiety disorders, which may lend support to the concept of primary versus secondary depression for purposes of differentiating treatment responses. Given the exploratory nature of the study, however, replication of our finding is needed.

Topics: Adult; Aged; Antidepressive Agents; Antidepressive Agents, Tricyclic; Anxiety Disorders; Diagnosis, Differential; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Mood Disorders; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Twenty women with premenstrual complaints were treated in a double-blind placebo controlled trial during two consecutive menstrual cycles with fluvoxamine, a selective serotonin uptake blocker. A beneficial effect was found on somatic and affective symptoms in both treatment groups, the effect of fluvoxamine being not different from placebo. The results of this study do not support a role for serotonin in menstrually related affective symptoms.

Topics: Antidepressive Agents; Anxiety; Double-Blind Method; Female; Fluvoxamine; Humans; Luteal Phase; Menstruation; Mood Disorders; Oximes

Fluvoxamine is commonly administered to patients with recurrent depressive disorder. Some of these patients do not show adequate response to the therapy with fluvoxamine, whereas many of them experience dose-dependent adverse drug reactions. Previous research revealed that CYP2D6 is involved in the metabolism of fluvoxamine, the activity of which is highly dependent on the polymorphism of the gene encoding it.. The objective of this study was to investigate the effect of polymorphisms of the CYP3A4, CYP2C9, CYP3A5, ABCB1, CYP2C19, SCL6A4, and 5-HTR2A genes on the concentration/dose indicator of fluvoxamine and on the CYP3A expression level obtained by measuring the miR-27b plasma concentration levels in patients suffering from a recurrent depressive disorder.. Our study included 105 patients with recurrent depressive disorder (average age - 37.5 ± 13.2 years). The treatment regimen included fluvoxamine in an average daily dose of 117.6 ± 44.3 mg per week. Therapy efficacy was assessed using the international psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels, we performed the real-time polymerase chain reaction. The activity of CYP3A was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of the given isoenzyme and its metabolite in urine (6b-HC/cortisol). Therapeutic drug monitoring has been performed using HPLC-MS/MS.. Our study didn't reveal any statistically significant results in terms of the treatment efficacy and safety of the therapy. We also didn't reveal a statistical significance for the concentration/dose indicator of fluvoxamine in patients with different genotypes. Analysis of the results of the pharmacotranscriptomic part of the study didn't demonstrate the statistically significant difference in the miR-27b plasma levels in patients with different genotypes. At the same time, correlation analysis didn't reveal a statistically significant relationship between the fluvoxamine efficacy profile evaluated by changes in HAMD scale scores and the miR-27b plasma concentration: r. Thus, the effect of genetic polymorphism of the CYP3A4, CYP2C9, CYP2C9, CYP3A5, ABCB1, CYP2C19, CYP2C19, CYP2C19, SCL6A4, 5-HTR2A gene on the efficacy and safety profiles of fluvoxamine was not demonstrated in a group of 105 patients with depressive disorder and alcohol use disorder.

Topics: Alcoholism; Biomarkers; Comorbidity; Cytochrome P-450 CYP3A; Fluvoxamine; Humans; MicroRNAs; Mood Disorders; Tandem Mass Spectrometry

Sigma1-receptors are an independent class of intracellular receptors which are implicated in the regulation of cell bioenergetics that suggest their involvement in different neuropsychiatric diseases. Sigma1-receptors regulate different ion channels, including calcium channels, NMDA-receptors, and are involved in the neurotransmitter release, neurogenesis and synaptogenesis. These receptors recognize with a different affinity a variety of ligands of different structural classes with different therapeutic applications. High affinity to sigma1-receptors may play an important role in the mechanism of action of some antidepressants, in particular fluvoxamine.

Topics: Antidepressive Agents; Central Nervous System; Fluvoxamine; Humans; Learning; Ligands; Mood Disorders; Receptors, sigma; Sigma-1 Receptor

There is evidence that combining selective serotonin reuptake inhibitor (SSRI) antidepressant and antipsychotic drugs may improve negative symptoms in schizophrenia and resistant symptoms in obsessive-compulsive and affective disorders. To examine the mechanism of action of this treatment we investigated the molecular modulation of γ-aminobutyric acid-A (GABA(A)) receptor components and biochemical pathways associated with GABA(A) receptor function following administration of the SSRI fluvoxamine (Flu) combined with the first-generation antipsychotic haloperidol (Hal) and compared it to the individual drugs and the atypical antipsychotic clozapine (Clz). We analysed prefrontal cortices of Sprague-Dawley rats injected intraperitoneally (i.p.) with the combination of Flu (10 mg/kg) and Hal (1 mg/kg), each drug alone, or Clz (10 mg/kg) after 30 min and 1 h. We found that haloperidol plus fluvoxamine (Hal-Flu) co-administration, and Clz, decreased the level of GABAAβ2/3 receptor subunit in the cytosolic fraction, and increased it in the membrane compartment in rat PFC. Flu or Hal alone did not produce changes in GABAAβ2/3 receptor protein expression. Additionally, Hal-Flu and Clz regulated molecular signalling pathways that modulate GABA(A) receptor function, including protein kinase C (PKC) and extracellular signal-regulated kinase-2 (ERK2). In primary cortical culture, short-term treatment (15 min) with Hal-Flu combination and Clz increased GABAAβ subunit phosphorylation levels. Pretreatment of the cells with PKC inhibitor abolished the effect of the combined treatment, or Clz on phosphorylation of GABA(A) receptor. Inhibition of ERK2 did not alter the effect of drugs on GABA(A) receptor phosphorylation levels. Our findings provide evidence that the combined treatment regulates GABA(A) receptor function and does so via a PKC-dependent pathway.

Topics: Animals; Antidepressive Agents; Antipsychotic Agents; Cells, Cultured; Clozapine; Dopamine; Drug Therapy, Combination; Fluvoxamine; Haloperidol; Male; Mitogen-Activated Protein Kinase 1; Mood Disorders; Obsessive-Compulsive Disorder; Phosphorylation; Prefrontal Cortex; Protein Kinase C; Rats; Rats, Sprague-Dawley; Receptors, GABA-A; Schizophrenia; Selective Serotonin Reuptake Inhibitors

A polymorphism within the serotonin transporter gene (SERTPR) has been repeatedly associated to mood disorders and response to SSRIs treatment. Recent evidence suggested that influence of genetic effect of SERTPR might be modulated by stress, particularly as regard the development of anxious-depressive symptoms. Nevertheless, there is no information about the role of stressors as potential modulator of SERTPR effects on depressive outcome during pharmacological treatment. In a sample of 159 mood disorder patients treated with fluvoxamine, we found stressors preceding the onset of the illness significantly influencing the genetic effect exerted by SERTPR on response after 6 weeks of treatment. This preliminary finding supports the idea of complex interaction between biological and environmental factors underlying the efficacy of biological treatments, other than liability for mood disorders. Nevertheless, many limitations characterize the present investigation and well-funded studies on larger samples are required.

Topics: Antidepressive Agents; Antidepressive Agents, Second-Generation; Bipolar Disorder; DNA; Fluvoxamine; Humans; Mood Disorders; Psychiatric Status Rating Scales; Serotonin Plasma Membrane Transport Proteins; Stress, Psychological

Several lines of evidence implicate abnormalities in glutamate neural transmission in the pathophysiology of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BP). Preclinical antidepressant effects were also reported for group II metabotropic glutamate receptor (Group II mGluRs) antagonists show dose-dependent antidepressant-like effects in murine models of depression. Also, it has been suggested that abnormalities in the hypothalamic-pituitary-adrenal axis and serotonergic neural transmission are important mechanisms in the pathophysiology of mood disorders. Group II mGluRs play an important role in regulating the function of these mechanisms. From these results, it has been suggested that abnormalities in Group II mGluRs might be involved in the pathophysiology of mood disorders, including MDD) and BP, and may influence the clinical response to treatment with SSRIs in MDD. Therefore, we studied the association between Group II mGluR genes (GRM2 and GRM3) and mood disorders and the efficacy of fluvoxamine treatment in Japanese MDD patients.. Using three tagging SNPs in GRM2 and an SNP (rs6465084) reported functional variant in GRM3, we conducted a genetic association analysis of case-control samples (325 MDD patients, 155 BP patients and 802 controls) in the Japanese population. In addition, we performed an association analysis of GRM2 and GRM3 and the efficacy of fluvoxamine treatment in 117 Japanese patients with MDD. The MDD patients in this study had scores of 12 or higher on the 17 items of the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D). We defined a clinical response as a decrease of more than 50% in baseline SIGH-D within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks.. We found an association between rs6465084 in GRM3 and MDD in the allele-wise analysis after Bonferroni's correction (P-value=0.0371). However, we did not find any association between GRM3 and BP or the fluvoxamine therapeutic response in MDD in the allele/genotype-wise analysis. We also did not detect any association between GRM2 and MDD, BP or the fluvoxamine therapeutic response in MDD in the allele/genotype-wise or haplotype-wise analysis.. We detected an association between only one marker (rs6465084) in GRM3 and Japanese MDD patients. However, because we did not perform an association analysis based on LD and a mutation scan of GRM3, a replication study using a larger sample and based on LD may be required for conclusive results.

Topics: Adult; Asian People; Case-Control Studies; Female; Fluvoxamine; Gene Frequency; Genome-Wide Association Study; Genotype; Haplotypes; Humans; Male; Middle Aged; Mood Disorders; Receptors, Metabotropic Glutamate; Young Adult

This preliminary study was performed to investigate the prevalence and severity of the serotonin-related symptoms for a group of patients in a clinical setting during fluvoxamine (FLU) using the Japanese version of the Serotonin Syndrome Scale (JSSS).. The subjects for the present study were 37 patients (20 and 17 patients with mood and anxiety disorders, respectively), meeting a diagnosis of DSM-IV. Each subject gave informed consent for the research involved in this study. Presence and severity of the serotonin-related symptoms were determined by Sternbach's criteria and the JSSS, respectively.. (1) At the time of assessment, none of the patients fulfilled the diagnostic criteria of SS proposed by Sternbach, or none of the total JSSS scores of the patients was sufficient to reach the cutoff point of 7. (2) Sixteen of the 37 patients (43.2%) showed at least one symptom in the JSSS. (3) Spearman's rank correlations showed that there was a positive but nonsignificant correlation between the total JSSS scores and dosages of FLU.. This preliminary study suggested that milder forms of the serotonin syndrome may exist for a group of patients in a clinical setting during FLU therapy.

Topics: Adult; Dose-Response Relationship, Drug; Female; Fluvoxamine; Humans; Male; Middle Aged; Mood Disorders; Prevalence; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome; Severity of Illness Index

We report nine cases where fluoxetine (FX) (20 mg/day) was added to maintenance treatment with methadone (MTD) (dose range: 30-100 mg) in addicts with affective disorders. MTD plasma levels were measured before and after treatment with FX under steady-state conditions. Among the nine patients, two also received fluvoxamine (FLVX) at different times. Although it is possible that in some patients a moderate FX-MTD interaction occurs, resulting in increased plasma levels of MTD, this interaction is certainly less marked than that between FLVX and MTD and unlikely to have clinical consequences.

Topics: Adult; Analgesics, Opioid; Antidepressive Agents, Second-Generation; Drug Interactions; Female; Fluoxetine; Fluvoxamine; Humans; Male; Methadone; Mood Disorders; Selective Serotonin Reuptake Inhibitors; Substance-Related Disorders

1 Plasma levels and platelet 5-HT uptake characteristics were determined at baseline and at various times during a long-term study comparing fluvoxamine and lithium prophylaxis. 2 In the fluvoxamine-treated patients after 12 and 24 weeks of treatment, Km was significantly increased and y, the mean overall uptake, significantly decreased compared to the patients' own baseline values and to lithium treatment. No significant change was noted for Vmax. 3 For fluvoxamine, significant negative relationships were established between the Vmax of platelet 5-HT uptake and plasma levels. 4 The trial had to be discontinued prematurely for some patients due to apparent lack of efficacy, unwanted effects or a combination of both in the fluvoxamine-treated patients. Low plasma levels of fluvoxamine may have contributed to the apparent lack of prophylactic efficacy of the drug. 5 Reference is made to the activity of receptor systems in patients receiving lithium and the consequent changes occurring after the administration of a potent 5-HT re-uptake inhibitor.

Topics: Antidepressive Agents; Blood Platelets; Double-Blind Method; Female; Fluvoxamine; Humans; Kinetics; Lithium; Male; Mood Disorders; Oximes; Serotonin