fluvoxamine and Depressive-Disorder--Major

A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to treat adults with major depressive disorder (MDD) in the maintenance phase. This study searched the PubMed, Cochrane Library, and Embase databases and included only double-blind, randomized, placebo-controlled trials with an enrichment design: patients were stabilized on the antidepressant of interest during the open-label study and then randomized to receive the same antidepressant or placebo. The outcomes were the 6-month relapse rate (primary outcome, efficacy), all-cause discontinuation (acceptability), discontinuation due to adverse events (tolerability), and the incidence of individual adverse events. The risk ratio with a 95% credible interval was calculated. The meta-analysis comprised 34 studies (n = 9384, mean age = 43.80 years, and %females = 68.10%) on 20 antidepressants (agomelatine, amitriptyline, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, vilazodone, and vortioxetine) and a placebo. In terms of the 6-month relapse rate, amitriptyline, citalopram, desvenlafaxine, duloxetine, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, and vortioxetine outperformed placebo. Compared to placebo, desvenlafaxine, paroxetine, sertraline, venlafaxine, and vortioxetine had lower all-cause discontinuation; however, sertraline had a higher discontinuation rate due to adverse events. Compared to placebo, venlafaxine was associated with a lower incidence of dizziness, while desvenlafaxine, sertraline, and vortioxetine were associated with a higher incidence of nausea/vomiting. In conclusion, desvenlafaxine, paroxetine, venlafaxine, and vortioxetine had reasonable efficacy, acceptability, and tolerability in the treatment of adults with stable MDD.

Topics: Adult; Amitriptyline; Antidepressive Agents; Citalopram; Depressive Disorder, Major; Desvenlafaxine Succinate; Duloxetine Hydrochloride; Female; Fluoxetine; Fluvoxamine; Humans; Mirtazapine; Network Meta-Analysis; Paroxetine; Randomized Controlled Trials as Topic; Reboxetine; Sertraline; Venlafaxine Hydrochloride; Vortioxetine

Previous studies suggested that the treatment response to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder follows a flat response curve within the therapeutic dose range. The present study was designed to clarify the relationship between dosage and treatment response in major depressive disorder.. The authors searched PubMed for randomized placebo-controlled trials examining the efficacy of SSRIs for treating adults with major depressive disorder. Trials were also required to assess improvement in depression severity at multiple time points. Additional data were collected on treatment response and all-cause and side effect-related discontinuation. All medication doses were transformed into imipramine-equivalent doses. The longitudinal data were analyzed with a mixed-regression model. Endpoint and tolerability analyses were analyzed using meta-regression and stratified subgroup analysis by predefined SSRI dose categories in order to assess the effect of SSRI dosing on the efficacy and tolerability of SSRIs for major depressive disorder.. Forty studies involving 10,039 participants were included. Longitudinal modeling (dose-by-time interaction=0.0007, 95% CI=0.0001-0.0013) and endpoint analysis (meta-regression: β=0.00053, 95% CI=0.00018-0.00088, z=2.98) demonstrated a small but statistically significant positive association between SSRI dose and efficacy. Higher doses of SSRIs were associated with an increased likelihood of dropouts due to side effects (meta-regression: β=0.00207, 95% CI=0.00071-0.00342, z=2.98) and decreased likelihood of all-cause dropout (meta-regression: β=-0.00093, 95% CI=-0.00165 to -0.00021, z=-2.54).. Higher doses of SSRIs appear slightly more effective in major depressive disorder. This benefit appears to plateau at around 250 mg of imipramine equivalents (50 mg of fluoxetine). The slightly increased benefits of SSRIs at higher doses are somewhat offset by decreased tolerability at high doses.

Topics: Citalopram; Depressive Disorder, Major; Dose-Response Relationship, Drug; Fluoxetine; Fluvoxamine; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

Topics: Aged; Antidepressive Agents; Aryl Hydrocarbon Hydroxylases; Aspirin; Clopidogrel; Comorbidity; Cytochrome P-450 CYP2C19; Depressive Disorder, Major; Drug Interactions; Drug Therapy, Combination; Early Diagnosis; Fluoxetine; Fluvoxamine; Gastrointestinal Hemorrhage; Genotype; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Factors; Selective Serotonin Reuptake Inhibitors; Ticlopidine

Agomelatine (Valdoxan) is licensed by the European Medicines Agency for the treatment of major depressive episodes in adults. The objective of this review was to consider how the drug should be used in clinical practice in particular starting, stopping and switching to and from the drug.. The existing clinical evidence was reviewed.. Data suggest that when switching to agomelatine from other antidepressants consideration should be given to tapering the previous antidepressant in order to minimize the risk of the original drug causing discontinuation/withdrawal symptoms. The risk of pharmacological interactions between most antidepressants and agomelatine is low and so tapering the previous antidepressant can usually be done after agomelatine has been started. An exception is fluvoxamine which should not be concurrently prescribed with agomelatine. As agomelatine appears to cause no significant discontinuation symptoms, it can probably be stopped abruptly when treatment is completed or when switching to another antidepressant.. While this guidance may change as clinical evidence and experience grows, currently agomelatine appears to have a good tolerability profile and is relatively easy to use, though prescribers should note the requirement to conduct liver function tests (LFTs) in accordance with the Summary of Product Characteristics (SPC).

Topics: Acetamides; Animals; Antidepressive Agents; Contraindications; Depressive Disorder, Major; Drug Interactions; Drug Monitoring; Fluvoxamine; Humans; Liver; Receptor, Melatonin, MT1; Receptor, Melatonin, MT2; Serotonin 5-HT2 Receptor Antagonists; Substance Withdrawal Syndrome

The purpose of this meta-analysis is to examine the relationship between selective serotonin reuptake inhibitor (SSRI) starting dose and treatment outcome in major depressive disorder (MDD). Medline/Pubmed, EMBASE, the Cochrane database, as well as a number of online clinical trial registries were searched for double-blind, placebo-controlled, fixed-dose trials comparing different starting doses of SSRIs for MDD. Data from nine trials (n=2340) were combined using a random-effects model. Patients randomized to receive the usual starting dose (10 mg escitalopram; 20 mg fluoxetine, paroxetine, citalopram; 50 mg sertraline and fluvoxamine) were less likely to respond than patients who received higher starting doses (RR=0.9; P=0.04; response rate 50.8 vs. 54.8%). The rate of discontinuation due to adverse events was lower among the usual starting dose group (9.8%) compared to the higher starting dose group (16.5%).Initiating treatment with SSRIs at doses higher than those typically used in clinical trials/settings is associated with higher response rates but also higher rates of discontinuation due to intolerance. Developing treatment strategies allowing clinicians to deliver higher initial SSRI doses while enhancing the tolerability of treatment may represent an alternative approach to improving the efficacy of treatment of MDD.

Topics: Citalopram; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Fluoxetine; Fluvoxamine; Humans; Paroxetine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

In a milnacipran study, ninety-six patients with major depressive disorder were treated with milnacipran, 50-100 mg/day, for 6 weeks. Severity of depression was assessed with the Montgomery and Asberg Depression Rating Scale. The purpose of this study was to determine whether norepinephrine transporter (NET) gene and serotonin transporter (5-HTT) gene polymorphisms are associated with the antidepressant response to milnacipran, a serotonin and norepinephrine reuptake inhibitor. Eighty patients completed the study. The presence of the T allele of the NET T-182C polymorphism was associated with a superior antidepressant response. In contrast, no influence of 5-HTTLPR (5-HTT linked polymorphic region) on the antidepressant response to milnacipran was detected. The results suggest that NET but not 5-HTT polymorphisms in part determine the antidepressant response to milnacipran. In a fluvoxamine study, sixty-six patients with major depressive disorder were treated with fluvoxamine, 100-200 mg/day, for 6 weeks. The authors investigated whether 5-HTTLPR was associated with the antidepressant response to fluvoxamine, a selective serotonin reuptake inhibitor. Fifty-seven patients completed the study. The short (s) allele frequency was significantly higher in the responsive individuals than in the nonresponsive ones. The results suggest that fluvoxamine is not less effective in depressive patients carrying the s allele than in those carrying the long (1) allele and it is not less effective in Japanese than in Caucasians.

Topics: Adult; Aged; Alleles; Antidepressive Agents; Cyclopropanes; Depressive Disorder, Major; Fluvoxamine; Forecasting; Humans; Male; Middle Aged; Milnacipran; Norepinephrine Plasma Membrane Transport Proteins; Pharmacogenetics; Polymorphism, Genetic; Promoter Regions, Genetic; Racial Groups; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins; Young Adult

The introduction of antidepressant drugs has revolutionized the treatment of mood disorders. However, even though sufficient doses of ADs have been used to treat depressive symptoms for sufficient periods, the treatment efficacy is considerably incomplete. The genetically determined investigation of pharmacological responses would be helpful to evaluate the best therapeutic tool for each depressed patient. However, the growing body of research in this field and heterogeneity across those studies could make it difficult for these candidates to be translated into treatment recommendations. Among other issues, the variety of ethnicity and therapeutic agents could play an important role as a confounder in pharmacogenetic results. To contribute to personalized medication for depression we should clarify the complicated, effect of these confounders. My colleagues and I reviewed the difference in genetic influence on antidepressant response between Asians and Caucasians based on a meta-analysis of pharmacogenetic studies. My colleagues and I also performed a randomized clinical trial (RCT) in Japanese subjects, "fluvoxamine vs paroxetine vs milnacipran," stratified by interesting genetic factors. The results showed that a pharmacogenetic approach could contribute, at least partially, to predict antidepressant response and personalized medication in depression with consideration of possible confounders.

Topics: Antidepressive Agents; Brain-Derived Neurotrophic Factor; Depressive Disorder, Major; Fibroblast Growth Factor 2; Fluvoxamine; Forecasting; Humans; Meta-Analysis as Topic; Paroxetine; Pharmacogenetics; Polymorphism, Genetic; Precision Medicine; Racial Groups; Randomized Controlled Trials as Topic; Receptor, Serotonin, 5-HT2A; Receptors, Adrenergic, alpha-2; Serotonin Plasma Membrane Transport Proteins

Antidepressants that enhance both serotonergic and noradrenergic neurotransmission may be more effective than selective serotonin reuptake inhibitors (SSRIs) for acute-phase therapy of major depressive disorder. Mirtazapine in particular has been suggested to have a faster onset of action than reuptake inhibitors. The aim of this study is to compare the remission rates and time to remission in patients with major depression taking either mirtazapine or an SSRI in an all-inclusive set of studies. Data were obtained from all eligible randomized controlled studies contrasting mirtazapine and SSRIs. Meta-analyses of remission rates and time to remission, together with a supportive analysis of mean change from baseline Hamilton Depression Rating Scales-17 were performed, using individual patient data from 15 randomized controlled trials of mirtazapine (N = 1484) versus various SSRIs (N = 1487) across 6 weeks of double-blind therapy. Analyses were repeated for the eight studies that lasted at least 8 weeks. Remission rates for patients treated with mirtazapine were significantly higher when compared with those treated with an SSRI after 1 (3.4 vs. 1.6%, P = 0.0017), 2 (13.0 vs. 7.8%, P<0.0001), 4 (33.1 vs. 25.1%, P<0.0001), and 6 weeks (43.4 vs. 37.5%, P = 0.0006) of treatment. Mirtazapine-treated patients had a 74% higher likelihood of achieving remission during the first 2 weeks of therapy compared with patients treated with SSRIs. In conclusion, the findings indicate that mirtazapine may be a more rapidly effective antidepressant than SSRIs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents, Tricyclic; Citalopram; Depressive Disorder, Major; Double-Blind Method; Female; Fluoxetine; Fluvoxamine; Humans; Male; Mianserin; Middle Aged; Mirtazapine; Paroxetine; Patient Dropouts; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Remission Induction; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome; Young Adult

Fluvoxamine, one of the oldest selective serotonin reuptaking inhibitors, is commonly prescribed to patients with major depression. Several studies have reviewed the efficacy and tolerability of fluvoxamine for the treatment of major depression. However, these reviews are outdated, have not been systematic and/or suffered from several methodological weaknesses. We conducted a systematic review to synthesize the best available evidence on the efficacy of fluvoxamine for adult patients suffering from major depression in comparison with other active antidepressive agents. Relevant randomized controlled trials were identified through a comprehensive search. The primary outcome was a relative risk of response, and the secondary outcome was a relative risk of remission. Tolerability and side-effect profile were also examined. Fifty-three trials were included. There were no large differences between fluvoxamine and any other antidepressants in terms of efficacy and tolerability. There is evidence of differing side effect profiles, especially when comparing gastrointestinal side effects between fluvoxamine and tricyclics. Clinicians should focus on practically or clinically relevant differences including those in side-effect profiles.

Topics: Adult; Antidepressive Agents, Second-Generation; Depressive Disorder, Major; Fluvoxamine; Humans; Randomized Controlled Trials as Topic; Treatment Outcome

To compare venlafaxine and selective serotonin reuptake inhibitors (SSRIs; fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram) in the treatment of depression.. Meta-analysis of 34 randomized, double-blind studies identified by a worldwide search of all research sponsored by Wyeth Pharmaceuticals through January 2007. Patients were treated with venlafaxine (n = 4191; mean dose 151 mg/day) or SSRIs (n = 3621); nine studies also included a placebo control group (n = 932). The primary outcome measure was intent-to-treat (ITT) remission rates (Hamilton Rating Scale for Depression

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Citalopram; Cyclohexanols; Depressive Disorder, Major; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Paroxetine; Randomized Controlled Trials as Topic; Remission Induction; Selective Serotonin Reuptake Inhibitors; Sertraline; Venlafaxine Hydrochloride

Topics: Adult; Antidepressive Agents; Bipolar Disorder; Citalopram; Commerce; Compulsive Behavior; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Middle Aged; Panic Disorder

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

Pharmacogenetics may allow for a personalized treatment, but a combination with clinical variables may further enhance prediction. In particular, in the present paper, we investigated early partial improvement (EPI) defined as 20% or more improvement by rating scales 2  weeks after treatment, in combination with selected gene variants as a predictor of treatment outcome in patients with major depressive disorder. Two randomized controlled trials with 168 Japanese depressed patients were used. A stepwise multiple linear regression model with HAM-D score change at week 6 as the dependent variable and genotypes, EPI, baseline HAM-D score, age and sex as independent variables was performed in paroxetine, fluvoxamine and milnacipran, respectively, to estimate the prediction of HAM-D change at week 6. In the paroxetine sample, only EPI (P<0.001) was significantly associated with HAM-D change (n=81, R(2)=0.25, P<0.001). In the fluvoxamine sample, 5-HTTLPR La/Lg, S (P=0.029), FGF2 rs1449683C/T (P=0.013) and EPI (P=0.003) were associated with HAM-D change (n=42, R(2)=0.43, P<0.001). In the milnacipran sample, HTR-1A-1019C/G (P=0.001), ADRA2A-1297C/G (P=0.028) and EPI (P<0.001) were associated with outcome (n=45, R(2)=0.71, P<0.001). EPI in combination with genetic variants could be a useful predictor of treatment outcome and could strengthen the practical use of pharmacogenetic data in clinical practice.

Topics: Age Factors; Antidepressive Agents; Antidepressive Agents, Second-Generation; Cyclopropanes; Depressive Disorder, Major; Female; Fibroblast Growth Factors; Fluvoxamine; Humans; Japan; Male; Middle Aged; Milnacipran; Paroxetine; Psychiatric Status Rating Scales; Receptor, Serotonin, 5-HT1A; Receptors, Adrenergic, alpha-2; Serotonin Plasma Membrane Transport Proteins; Sex Factors; Treatment Outcome

This study was undertaken to examine the long-term effectiveness and safety of switching to sertraline from other selective serotonin reuptake inhibitors (SSRIs) in the treatment of non-remitted or treatment-intolerant major depressive disorder. The study included 25 patients with major depressive disorder according to DSM-IV-TR criteria. None had achieved remission with paroxetine or fluvoxamine, but each had been used in an adequate dose for an adequate time period or had been intolerant of these SSRIs. Most patients (n=22, 88%) were non-remitters. Switching was accomplished by gradual cross-titration and tapering. We conducted assessments at baseline and at weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24. Outcomes were assessed using the Quick Inventory of Depressive Symptomatology-Self-Report, Japanese version (QIDS-SRJ) score (primary outcome), the 17-item Hamilton Depression Rating Scale (HDRS), and the Clinical Global Impressions (CGI) scale. Mean QIDS-SRJ and HDRS scores improved significantly from baseline to week 8 and week 24. At the respective endpoints of weeks 8 and 24, remitters on QIDS-SRJ (≤5) were 2 of 25 (8%) and 4 of 25 (16%). At weeks 8 and 24, 11 of 25 (44%) were responders on QIDS-SRJ (≥50% reduction). Five patients (20%) terminated early, before week 8, because of side effects and/or lack of efficacy. These preliminary data suggest that the switching strategy from paroxetine or fluvoxamine to sertraline might be effective and well-tolerated in patients with non-remitted or treatment-intolerant major depressive disorder.

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

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

The aim of this prospective study was to verify whether magnetostimulation with weak variable magnetic fields with low value of induction could enhance the effects of pharmacological therapy in drug-resistant depression.. Thirty patients, 26 women and 4 men, with drug-resistant depression were enrolled in the study. The subjects from Group No. I (14 patients) were given fluvoxamine and treated with weak variable magnetic field using the VIOFOR JPS device; the subjects from Group No. II (16 patients) were also given fluvoxamine but they were treated with the VIOFOR JPS device in placebo mode. Changes in depressive symptoms were estimated with the 21-point Hamilton Depression Scale (HDRS), Montgomery-Asberg Depression Scale (MADRS) and Beck Depression Inventory (BDI) questionnaire.. After 15 days of treatment highly significant differences were revealed between the patients treated with magnetic field and the patients treated with placebo: the final HDRS score was 53% of the initial value for the group receiving combined treatment, and 86% in the placebo group (p<0.001); for MADRS score the values were 51% and 88% (p<0.001), respectively, and for BDI 60% and 87% (p<0.001). Thus, the average effect of placebo applied with fluvoxamine was a ca. 15% reduction of symptoms, while the concurrent application of magnetic field and SSRI treatment resulted in a 40-50% improvement.. Our study indicates that adding a two-week low-induction variable magnetic field stimulation to a classical pharmacologic therapy reduces the intensity of symptoms in patients with drug-resistant depressive disorders.

Topics: Adult; Antidepressive Agents, Second-Generation; Combined Modality Therapy; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Female; Fluvoxamine; Humans; Male; Middle Aged; Personality Inventory; Prospective Studies; Transcranial Magnetic Stimulation

The aim of this study was to analyze the relation between treatment response and the duration of untreated illness (DUI) in 133 outpatients with the first major depressive disorder (MDD) episode.. A logistic regression was performed with DUI, sex, age at onset, and score for 17 items on the Hamilton Depression Rating Scale at the time of start of fluvoxamine treatment as the explanatory variables, and the response and the remission as the outcome variables.. Regression analysis showed significant association between the response and DUI (P < 0.0001), and between the remission and DUI (P < 0.0001), respectively. The remission rate gradually decreased with longer DUI.. Early treatment of first depressive episodes is important because a shorter DUI implied better remission outcomes.

Topics: Adult; Age of Onset; Aged; Antidepressive Agents; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Middle Aged; Time Factors; Treatment Outcome

Until now no studies have investigated the benefits of adding brief dynamic therapy (BDT) to medication in obsessive-compulsive disorder (OCD), while a number of recent investigations have demonstrated the efficacy of supplemental BDT among patients with major depressive disorders (MDD). The objective of the present study was to explore the efficacy of BDT combined with pharmacotherapy in comparison with pharmacotherapy alone in the treatment of OCD with concurrent MDD.. A 12-month randomized clinical trial compared a standard selective serotonin reuptake inhibitor treatment with (n = 27) or without (n = 30) supplemental BDT in patients with OCD and concurrent MDD. Supplemental BDT was added during the first 16-week trial; all patients continued to be treated with only pharmacotherapy in the following continuation phase. The primary efficacy assessments were the Yale-Brown Obsessive Compulsive Scale and the 17-item Hamilton Rating Scale for Depression; the secondary efficacy measures included the Clinical Global Impression scale and the Global Assessment of Functioning. The data analysis was conducted on the 'intent-to-treat (ITT) efficacy patient sample'.. Fifty patients completed the study. No difference between the 2 treatment groups was found at any point by any assessment method in the ITT study sample.. Supplemental BDT in the treatment of patients with OCD with concurrent MDD who are receiving effective medication has no significant clinical effect on both obsessive and depressive symptoms.

Topics: Adult; Combined Modality Therapy; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Obsessive-Compulsive Disorder; Psychiatric Status Rating Scales; Psychotherapy, Brief; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

Although often necessary for obtaining remission following major depressive disorder, combined antidepressant treatment is frequently associated with drug interactions and enhanced adverse drug effects. We investigated pharmacokinetic interactions following combined fluvoxamine and amitriptyline treatment and their impact on therapeutic efficacy and tolerability. Twenty-two inpatients with major depression [Hamilton Depression Scale (HAM-D) rating > or =18] were treated with either amitriptyline (75 mg/day), fluvoxamine (100 mg/day) or both. Blood samples, for determination of amitriptyline, its major metabolite nortritpyline, and fluvoxamine, were obtained after single dose administration and in steady-state. Therapeutic efficacy was evaluated using HAM-D and adverse drug effects were evaluated using the clinical global impression scale. Following combined treatment, steady-state plasma levels of nortriptyline were significantly decreased compared to monotherapy. HAM-D scores after two-week treatment showed that there was a better response to combined treatment. There was no significant difference in severity of adverse effects among groups. We observed a pharmacokinetic interaction between fluvoxamine and amitritpyline resulting in impaired metabolism of the later. However, no significant impact of the interaction on treatment safety was observed. Moreover, concomitant use of amitriptyline at 75 mg/day and fluvoxamine at 100 mg/day was well tolerated with a more prompt and stronger onset of clinical response compared to monotherapy in patients with major depression.

Topics: Adult; Amitriptyline; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Depressive Disorder, Major; Drug Interactions; Drug Therapy, Combination; Female; Fluvoxamine; Half-Life; Humans; Male; Middle Aged; Psychiatric Status Rating Scales

The efficacy of SSRIs in relapse prevention in major depression has been extensively demonstrated. Considering published data, the relapse rate during a psychopharmacological continuation treatment ranges from 10% to 30%. Since the reasons of depressive relapses could be heterogeneous, we have tested the effect of clinical, psychosocial and genetic variables in sustained remission from an index depressive episode during continuation treatment with fluvoxamine over a 6-month follow-up period. 101 patients maintained the same full dosage treatment after remission from a depressive episode efficaciously treated with fluvoxamine. During the follow-up period, they were clinical assessed monthly by an experienced psychiatrist and SASS was administered, to assess their psychosocial adjustment. From a genetical point of view, SERTPR and CLOCK polymorphisms were analyzed for each patients, using PCR-based techniques. At the end of follow-up period, the 57.4% of the patients maintained remission during fluvoxamine continuation treatment; the 8.9% relapsed within the first 2 months of continuation; the 7.9% switched and the 25.8% dropped-out for poor compliance. Relapsed subjects presented a significantly longer mean duration of the index depressive episode than non-relapsed subjects and a subjective poor social adjustment than non-relapsed also in the euthymia period. None of the analyzed polymorphisms significantly appear to influence the outcome of the whole sample. The present data confirm that patients with severe depression and a long duration of the episode have a major risk of psychosocial disability. These patients could need a different psychopharmacological strategies and peculiar psychological intervention.

Topics: Adult; Aged; Analysis of Variance; Antidepressive Agents, Second-Generation; Depressive Disorder, Major; DNA Mutational Analysis; Female; Fluvoxamine; Follow-Up Studies; Humans; Italy; Logistic Models; Male; Middle Aged; Psychiatric Status Rating Scales; Retrospective Studies; Secondary Prevention; Treatment Outcome

To investigate whether the addition of triiodothyronine (T3) helps relieve depressive symptoms in non-hypothyroid major depressive disorder patients who failed to respond to an adequate course of standard SSRI antidepressant treatments.. Patients who fulfilled the DSM-IV criteria for non-psychotic major depression, able to give informed consent, and failed to show satisfactory antidepressant response after a minimum of six weeks adequate treatment were recruited. To enter the study their Hamilton Depression (17-item HAMD) score had to be 18 or more, thyroid-stimulating hormone (TSH) value within the normal range, and a normal thyrotropin releasing hormone-stimulation test (TRH-ST). All patients continued taking the same SSRI which they had been taking before they entered the study. At the completion of TRH-SH they were all started on 25 microg of T3 and the dose was increased to 50 microg within a week when tolerated; they continued the combination of T3 and the SSRI for a minimum of three weeks.. Twelve patients, comprising eight females and four males, entered the study. One female patient withdrew during the first week of side effects, eleven patients completed the trial. The patients ranged from 26 to 77 years of age, with the mean age for males and females being 52.3 and 45.1 years, respectively. Five patients were taking sertraline (mean dose = 130 mg/day) and 4 were taking citalopram (mean dose = 50 mg/day), two were on fluvoxamine (150 mg/day) and one patient was on 40 mg of paroxetine. The women took a mean daily dose of 40.6 microg of T3 for a mean duration of 3.75 weeks, while the men were on a mean daily dose of 43.8 mug of T3 for 3.5 weeks. T3 augmentation was associated with a statistically significant drop (p < .003) in the mean HAMD at end of the three weeks compared to baseline scores. Five patients (42%) showed >or=50% improvement on HAMD scores, with three achieving full remission (HAMD scores

Topics: Adult; Aged; Citalopram; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Drug Administration Schedule; Drug Resistance; Female; Fluvoxamine; Humans; Male; Middle Aged; Paroxetine; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Triiodothyronine

Lithium augmentation of antidepressant effects in patients unimproved on antidepressants is well documented. We hypothesized that phenytoin, reported to have antimanic, antidepressant and prophylactic effects on affective disorder, might also augment in SSRI failures.. Twenty five patients were recruited and twenty had data sufficient for analysis between phenytoin and placebo in depression ratings.. No effect was found.. This study was a small study.. Lithium's ability to augment in antidepressant failures may not be shared with the anticonvulsant mood stabilizers.

Topics: Adult; Aged; Anticonvulsants; Depressive Disorder, Major; Double-Blind Method; Drug Resistance; Drug Therapy, Combination; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Paroxetine; Personality Inventory; Phenytoin; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Topics: Antidepressive Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Blood Pressure; Depressive Disorder, Major; Double-Blind Method; Drug Resistance; Female; Fluvoxamine; Humans; Hypotension, Orthostatic; Imipramine; Male; Middle Aged; Monoamine Oxidase Inhibitors; Phenelzine; Psychiatric Status Rating Scales; Tranylcypromine; Treatment Outcome

A part (60% to 70%) of those who are going to act out their suicide consult a doctor the month before. Studies have shown the need to improve the practitioner's capacity to diagnose depression. The assessment of the suicidal risk is crucial. The search for suicidal risk factors helps to define the populations at risk. However, it doesn't provide information concerning the possibility of acting out in the short term. And how does one react when faced with those who do not present any of the risk factors? Psychometric instruments attempt to help the therapist in his/her reasoning. SUICIDAL RISK ASSESSMENT: Among them, the suicidal risk assessment scale RSD should be mentioned. Its objective is to estimate the seriousness of the suicidal risk, with 11 levels. It is built around a possible will to commit suicide rather than a single assessment of the frequency of suicidal ideas. Its construction in hierarchical order permits the progressive assessment of the suicidal risk, in the form of a semi-structured interview. Hence, the suicidal risk assessment scale RSD looks for the existence of death wishes (levels 1-2), of suicide ideations and its frequency (levels 3-4-5), and of a passive desire to die (level 6). Level 7 shows the onset of a decision making process, except that the patient is still inhibited by various important factors in his/her life. More often, the fear of inflicting immense suffering to his/her loved ones or for religious beliefs, is found. From level 8, determination has made way to hesitation. An active death wish exists, and although the plan remains undefined, the act is decided on. At level 9 the methods of application are developed and a plan is established. The ultimate level exists when there is a start in the preparation of the act of suicide (level 10). This hierarchical order has been confirmed by some epidemiological studies.. The inclusion of the suicidal risk assessment scale RSD in a double-blind, placebo-controlled study, which tested the efficacy of fluvoxamine in reducing the risk of recurrence of depression over 18 months, appears of particular interest. In this multicentre study, patients of both sexes were included, aged between 18 and 70 years, presenting a major depressive episode with a MADRS equal to a minimum of 25, and having had a minimum of two episodes of major depression within the last five years.. The resulting analysis carried out on 103 patients showed a satisfactory concurrent validity between the suicidal risk assessment scale RSD and the items "suicide" of the MADRS (rho=0.79; p=0.0001) and the Hamilton Depression Scale (rho=0.70; p=0.0001), and fairly satisfactory concurrent validity with the depression degree assessed by the MADRS overall score (rho=0.40; p=0.0001). The short-term follow-up under treatment revealed enhanced sensitivity of the RSD versus the MADRS. The improvement in suicidal risk, assessed by the RSD, was faster than the improvement in depression, which is interesting from a clinical point of view. The medium-term follow-up tested the predictive validity of RSD and confirmed a greater level of suicidal risk from a score of 7 on the RSD, with the death by suicide of 2 subjects among the 15 who exhibited a score between 7 and 10 on the RSD on inclusion. On the other hand, no acting out, no attempted suicides, and no suicides were noted in the group of 88 subjects whose RSD was lower or equal to 6 on inclusion (p=0.02 using Fisher's exact test).. Thus, the RSD appears of interest, from a clinical point of view, by providing a -diagnostic, or a scientific approach.

Topics: Adult; Antidepressive Agents, Second-Generation; Depressive Disorder, Major; Double-Blind Method; Female; Fluvoxamine; Follow-Up Studies; Humans; Interview, Psychological; Male; Middle Aged; Personality Assessment; Personality Inventory; Psychometrics; Reproducibility of Results; Risk Assessment; Secondary Prevention; Suicidal Ideation; Suicide; Suicide Prevention

Vesicle-associated membrane protein 2 (VAMP2) is a key component of the synaptic vesicle docking/fusion machinery and its mRNA reportedly increases in the frontal cortex of rats following chronic antidepressant and electroconvulsive treatment. VAMP2 is therefore thought to be involved in the mechanism of action of antidepressants and may alter their efficacy. The purpose of this study was to investigate whether the VAMP2 gene is associated with clinical responses to a specific antidepressant, fluvoxamine.. A total of 106 patients with major depressive disorder were given fluvoxamine (50-200 mg/day) for 8 weeks and assessed for severity of depression using the Semi-Structured Interview Guide of the Hamilton Depressive Scale (SIGH-D; 17 items) at 0 and 8 weeks. We defined a clinical response as more than a 50% reduction in baseline SIGH-D within 8 weeks, and defined clinical remission as a SIGH-D score of less than 7 at 8 weeks. Genotyping was performed by PCR-RFLP.. Analysis of haplotype tagging single nucleotide polymorphisms as well as haplotype analysis did not reveal any significant associations.. Our results suggest that the VAMP2 gene is unlikely to play a major role in the efficacy of fluvoxamine.

Topics: Adult; Chi-Square Distribution; Depressive Disorder, Major; Female; Fluvoxamine; Gene Frequency; Genotype; Humans; Japan; Male; Middle Aged; Polymorphism, Single Nucleotide; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Vesicle-Associated Membrane Protein 2

The aim of this study was to compare the efficacy and safety profiles between fluvoxamine and nortriptyline in Japanese patients with major depression.. The efficacy and safety profiles of fluvoxamine, a selective serotonin-reuptake inhibitor, and nortriptyline were compared under a single-blind fashion in 74 Japanese patients with major depression. The efficacy was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impression Scale (CGI) severity and improvement scores, while the safety profiles were assessed using the UKU Side Effect Rating Scale at baseline, and on days 7, 14, 28 and 56. Moreover, with the aim of determining the distinct efficacy profiles of each drug, the effects on each of the factor scores extracted by the principal component analysis performed for HAM-D scores were compared between drugs.. Both drug groups showed significant amelioration of depressive symptomatology over the trial period lasting for 8 weeks. Statistical analyses revealed no significant between-group differences regarding the efficacy assessed by either HAM-D or CGI scores; however, the efficacy of nortriptyline tended to appear earlier than that of fluvoxamine. Moreover, no significant differences were obtained for the factor scores, representing 'depressed mood', 'physical symptoms' or 'sleep disturbances', although 'sleep disturbances' appeared to improve earlier in the nortriptyline group than in the fluvoxamine group. As for the safety profiles, the nortriptyline group scored a significantly higher incidence of adverse events such as dysarthria or orthostatic dizziness, as well as increased heart rate.. These findings suggest that fluvoxamine is generally comparable to nortriptyline in its efficacy and superior in its safety profile, in accordance with findings obtained in previous comparative clinical trials conducted in Caucasian populations.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Depressive Disorder, Major; Double-Blind Method; Female; Fluvoxamine; Humans; Japan; Male; Middle Aged; Nortriptyline; Psychiatric Status Rating Scales

Imipramine has often been used as positive control in studies investigating the efficacy of new antidepressants. Imipramine-controlled studies in general employ a fixed-dose design. It is unclear how many patients would achieve effective plasma levels with such a design.. The objectives of this study were to assess the range of doses necessary to attain a therapeutic plasma level in the imipramine arms of two double-blind, fixed-plasma-level studies and to compare them with doses administered in efficacy studies with imipramine as a positive control.. During two double-blind studies, imipramine doses were adjusted to a predefined fixed plasma level. Here we report an analysis of the range of doses necessary to attain that level in the imipramine arms of the studies. We also computed the cumulative percentage of patients with therapeutic plasma levels (> or = 200 ng/ml) at various imipramine doses in order to compare them with doses administered in efficacy studies with imipramine as a positive control.. Target plasma levels were attained with a mean daily dose of 248 mg, with a dose range of 50-450 mg. We calculated a possible increase in efficacy of imipramine of about 20% if doses had been adjusted to therapeutic plasma levels in clinical trials using it as a positive control.. The absence of significant differences in efficacy between selective serotonin re-uptake inhibitors (SSRIs) and imipramine in these trials is at least in part due to improper dosing of the latter; imipramine with therapeutic drug monitoring may be more effective than SSRIs.

Topics: Adult; Aged; Antidepressive Agents, Tricyclic; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluvoxamine; Humans; Imipramine; Male; Metabolic Clearance Rate; Mianserin; Middle Aged; Mirtazapine; Treatment Outcome

Major depression is a common psychiatric disorder in the elderly population. The efficacy of tricyclic antidepressants is well established, and selective serotonin reuptake inhibitors appear to have a similar effectiveness along with advantages in terms of tolerability and safety. Given the lack of literature data regarding fluvoxamine in the treatment of depressed elderly patients, the aim of the present study was to compare its efficacy and tolerability with those of sertraline in a sample of elderly patients.. Under double-blind conditions, 93 hospitalized patients older than 59 years, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a major depressive episode, were randomly assigned to receive sertraline (150 mg daily) or fluvoxamine (200 mg daily) for 7 weeks. The clinical response was defined as a reduction on the Hamilton Rating Scale for Depression score to 8 or below.. At study completion, the response rates were 55.6% (25/45) and 71.8% (28/39) for sertraline and fluvoxamine, respectively. No significant difference in final response rates was found between the 2 treatment groups (P = 0.12). A repeated-measures analysis of variance on Hamilton Rating Scale for Depression scores revealed a significantly different decrease of depressive symptoms between the 2 treatment groups, favoring fluvoxamine (P = 0.007). The overall safety profile of sertraline and fluvoxamine was favorable with no differences between the 2 drugs.. The results of this double-blind trial show that sertraline and fluvoxamine may be effective compounds in the treatment of elderly depression with the latter showing some advantage in terms of speed of response. These findings warrant further replication in placebo-controlled studies.

Topics: Aged; Antidepressive Agents, Second-Generation; Depressive Disorder, Major; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Sertraline

To evaluate the safety, tolerability, and benefit of fluvoxamine for the treatment of major depressive disorder or anxiety disorders in children and adolescents with cancer.. The study was conducted from 2001 to 2004 at a pediatric hematology-oncology center. Fifteen children and adolescents with cancer were treated with fluvoxamine 100 mg/day in an open prospective 8-week trial. Safety and tolerability were evaluated at baseline and at weeks 4 and 8 by blood tests and the Side Effects Checklist. Clinical benefit was assessed with the Clinical Global Impressions-Improvement, the Children's Depression Rating Scale-Revised, and the Pediatric Anxiety Rating Scale.. Fluvoxamine was well tolerated by all subjects. Psychiatric symptoms improved significantly.. In this open trial, fluvoxamine appeared to be well tolerated and was associated with a promising reduction in the depression and anxiety symptoms of pediatric patients with cancer.

Topics: Adolescent; Anti-Anxiety Agents; Antidepressive Agents, Second-Generation; Anxiety Disorders; Child; Depressive Disorder, Major; Fluvoxamine; Follow-Up Studies; Humans; Neoplasms; Pilot Projects; Selective Serotonin Reuptake Inhibitors; Sick Role

Diminished HR variability is considered to be associated with depression and the increased risk of cardiovascular disease. The pharmacological effects of antidepressants and depressive mood itself may contribute to alterations in autonomic cardiac functioning, but a limited amount of data is available. We studied the effects of two different types of antidepressant treatments (imipramine and fluvoxamine), in addition to the effect of depressive mood, on the cardiovascular system in depressed patients.. Depressed inpatients were studied during a drug-free period and after 4 weeks of adequate treatment with imipramine (n = 17) or fluvoxamine (n = 24). Heart rate variability, blood pressure variability, and a baroreflex sensitivity index during supine rest and orthostatic challenge were analyzed by means of spectral techniques to obtain noninvasive parameters of sympathetic and parasympathetic activity.. Both imipramine and fluvoxamine reduced sympathetic and parasympathetic activity, although the effects of imipramine were much more pronounced. Severity of depression was positively related to mean levels of heart rate and blood pressure in the total patient group. There was no convincing evidence that these relationships differed between depressed patients treated with imipramine and those treated with fluvoxamine.. Our findings suggest that alterations in mean heart rate and blood pressure in depressed patients after antidepressant treatment are the result of a combined effect of pharmacological actions of antidepressants and improvement of depressive mood state. The present study did not confirm the relationship between clinical state and cardiovascular variability or baroreflex sensitivity.

Topics: Adult; Affect; Aged; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Autonomic Nervous System; Blood Pressure; Depressive Disorder, Major; Double-Blind Method; Electrocardiography; Female; Fluvoxamine; Heart; Heart Rate; Humans; Imipramine; Male; Middle Aged; Personality Inventory; Treatment Outcome

To compare the efficacy of imipramine and fluvoxamine in inpatients from two centers suffering from a depressive disorder according to DSM IV criteria.. The study included 141 patients with a depressive disorder according to DSM IV criteria. After a drug-free and placebo run-in period of 1 week, patients were randomized to imipramine or fluvoxamine; doses of both drugs were adjusted to a predefined target blood level. Efficacy was evaluated 4 weeks after attaining predefined adequate plasma level.. The mean age of the study group (47 males, 94 females) was 51.8 (range 19-65) years. Of these 141 patients, 56 had episode duration longer than 1 year, 48 had mood congruent psychotic features, and 138 patients received medication. Seven patients did not complete the medication trial. The total number of patients using concurrent medication was 12/138 (8.6%). On the primary outcome criteria patients on imipramine improved significantly better on the change of illness severity score of the CGI (chi2 exact trend test=4.089, df=1, P=-0.048). There was no significant difference in 50% or more reduction on the HRSD, the other primary outcome criterion. On the secondary outcome criteria the mean reduction of the HRSD scores was significantly larger in the imipramine group than in the fluvoxamine group (mean difference=3.1, standard error (SE)=1.4, t=2.15, df=136, P=0.033). There was no significant difference in the number of patients with an HRSD < or =7 at the final evaluation.. In depressed inpatients imipramine is more efficacious than fluvoxamine. Both drugs were well tolerated by all patients.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Depressive Disorder, Major; Double-Blind Method; Female; Fluvoxamine; Humans; Imipramine; Inpatients; Male; Middle Aged; Patient Compliance; Patient Dropouts; Psychiatric Status Rating Scales; Treatment Outcome

Fluvoxamine 200 mg was administered for 3 months to a group of 43 interferon beta-1b treated patients affected by major depression associated with multiple sclerosis. Despite a 16.3% attrition rate, 79% of patients achieved response. The drug was well tolerated.

Topics: Adjuvants, Immunologic; Adult; Depressive Disorder, Major; Drug Administration Schedule; Female; Fluvoxamine; Follow-Up Studies; Humans; Interferon beta-1b; Interferon-beta; Male; Mental Status Schedule; Middle Aged; Multiple Sclerosis; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Treatment Outcome

This study was designed to compare the efficacy of two two-phase pharmacological treatment strategies for inpatients with DSM-IV major depressive disorder.. During phase I, patients participated in a double-blind study of the effects of imipramine versus fluvoxamine, with final evaluation of response 4 weeks after patients attained the target plasma level. In phase II, for patients without treatment response or with partial response in phase I, lithium was added to imipramine or fluvoxamine. Final evaluation of response was made 3 weeks after the patients attained the target plasma level of lithium (0.6-1.0 mmol/liter).. One hundred thirty-eight patients were enrolled in the study. At the end of phase I, remission, defined as a final Hamilton Depression Rating Scale score < or =7, was achieved by 16 (23%) of 70 imipramine-treated patients and 10 (15%) of 68 fluvoxamine-treated patients. At the end of phase II, 41 (59%) of 70 imipramine-treated patients versus 27 (40%) of 68 fluvoxamine-treated patients qualified for remission, a significant difference in favor of the imipramine strategy. Only a small minority of both groups received concomitant medication. In both phase I and phase II, the discontinuation rate was low (5% and 10%, respectively).. Imipramine with subsequent lithium addition is superior to a similar strategy with fluvoxamine for treatment of severely depressed inpatients. Both strategies were well tolerated.

Topics: Adult; Aged; Antidepressive Agents, Tricyclic; Depressive Disorder, Major; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluvoxamine; Hospitalization; Humans; Imipramine; Lithium; Male; Middle Aged; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Treatment Outcome

Inhibitors of steroid synthesis have been reported to exert antidepressive effects, according to preliminary findings.. To test whether the addition of metyrapone to standard antidepressants induces a more rapid, more efficacious, and sustained treatment response in patients with major depression.. Double-blind, randomized, placebo-controlled trial.. Hospitalized care.. Sixty-three inpatients with a DSM-IV diagnosis of major depression and a baseline score 18 points or higher on the Hamilton Rating Scale for Depression.. Random allocation to 2 treatment groups receiving either placebo or metyrapone (1 g/d) for the first 3 weeks during a 5-week treatment with standard serotonergic antidepressants (nefazodone or fluvoxamine).. Primary outcome criteria were the number of responders and the time to onset of action. Responder rates were considered twice after 3 and 5 weeks with a definition of treatment response as 30% and 50% reduction, respectively, of baseline Hamilton Rating Scale for Depression scores. Onset of action was defined as the time point at which at least a 20% reduction of baseline Hamilton Rating Scale for Depression scores occurred.. Using intention-to-treat analysis, we found that a higher proportion of patients receiving metyrapone showed a positive treatment response at day 21 (23 of 33 patients) and at day 35 (19 of 33 patients) compared with placebo patients (day 21: 13 of 30 patients; Fisher exact P = .031; day 35: 10 of 30 patients; Fisher exact P = .047). The clinical course of patients treated with metyrapone showed an earlier onset of action (Kaplan-Meier analysis; log-rank test P<.006) beginning in the first week. The plasma concentrations of corticotropin and deoxycortisol were significantly higher during metyrapone treatment (multivariate analysis of covariance, P<.05), whereas cortisol remained largely unchanged. Metyrapone treatment was well tolerated without serious adverse effects.. Metyrapone is an effective adjunct in the treatment of major depression, accelerating the onset of antidepressant action. A better treatment outcome compared with standard treatment and a sustained antidepressive effect were observed.

Topics: Adrenocorticotropic Hormone; Adult; Antidepressive Agents; Cortodoxone; Dehydroepiandrosterone; Depressive Disorder, Major; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Enzyme Inhibitors; Female; Fluvoxamine; Humans; Male; Metyrapone; Middle Aged; Piperazines; Placebos; Psychiatric Status Rating Scales; Treatment Outcome; Triazoles

The aim of the study was to compare the efficacy and tolerance of fluvoxamine (FL) and amitriptyline (AM) in the treatment of patients hospitalized for moderate and severe depression and to evaluate the spectrum of antidepressive activity in FL. The study was open, randomized and comparative. Sixty patients (mean age 41 +/- 2.9 years) diagnosed as having recurrent depressive disorder, a moderate or severe depressive episode (ICD-10 F33.1, F33.2) were divided into two equal groups treated with FL or AM. The efficacies of FL and AM were comparable, with AM exhibiting an earlier clinical effect and FL having a better tolerance. FL was defined as an antidepressant with the predominantly sedative effect comparable to that of AM, but being better tolerated.

Topics: Adolescent; Adult; Aged; Amitriptyline; Antidepressive Agents, Tricyclic; Depressive Disorder, Major; Drug Tolerance; Female; Fluvoxamine; Hospitalization; Hospitals, Psychiatric; Humans; International Classification of Diseases; Male; Middle Aged; Selective Serotonin Reuptake Inhibitors

An investigation of the characteristics of patients being treated with antidepressants would seem to be useful in determining which patients would be most likely benefit from antidepressant medication.. The purpose of this preliminary study was to examine the possible predictors of response to fluvoxamine for depression.. A retrospective cohort analysis was carried out among depression patients treated in the Department of Psychiatry, Kawasaki Medical School Hospital, Kurashiki, Japan, in 2000. Seventy two patients were identified who were receiving fluvoxamine to treat depression.. A variety of clinical factors including age, gender, type of depression, frequency of episodes, family history and daily dose of fluvoxamine were examined as possible predictors of the response to fluvoxamine. A Weibull regression analysis showed age, frequency of episodes and daily dose to be the independent predictive factors of improvement in fluvoxamine treatment. The most influential factor was age (ecoef = 2.109), followed by daily dose (ecoef = 0.648) and frequency of episode (ecoef = 0.512). An age of 49 years or younger (chi(2) = 6.767, df = 1, p = 0.0093), a first episode (chi(2) = 9.079, df = 1, p = 0.0026) and a daily dose of 100-150 mg (chi(2) = 5.353, df = 1, p = 0.02) were significantly better predictors of improvement.. Age, the frequency of episodes and the daily dose of fluvoxamine may be considered as predictors of the response to fluvoxamine treatment for depression. This result should be examined in future prospective study.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents, Second-Generation; Cohort Studies; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Middle Aged; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

The relationship between clinical effects of fluvoxamine (FLV) and the steady-state plasma concentrations (Css) of FLV and its major metabolite fluvoxamino acid (FLA) was studied.. The subjects were 49 Japanese patients with major depressive disorder receiving FLV 200 mg/day for 6 weeks. Depressive symptoms and side effects were evaluated by the Montgomery Asberg Depression Rating Scale (MADRS), and the UKU Side Effect Rating Scale, respectively. The Css of FLV and FLA were measured by HPLC, and the CYP2D6 genotyping was performed by PCR methods.. The Css of FLV and FLV+FLA showed significant negative correlations with the final MADRS score. The Css of FLV, FLA and FLV+FLA were significantly higher in the responders (final MADRS score < or =10) than in non-responders. The proportion of responders was significantly higher in the patients with the Css of FLV, FLA and FLV+FLA above 150, 55 and 180 ng/ml, respectively. In the multiple regression, the Css of FLV+FLA showed a significant negative correlation with the final MADRS score. In the logistic regression, the Css of FLA had a significant effect on the differentiation of responders from non-responders. The incidence of side effects was low, and the development of nausea, the most frequent one, was not dependent on any Css. The number of mutated CYP2D6 alleles causing absent or decreased enzyme activity was not related to the therapeutic response or development of nausea.. The present study suggests that there is a therapeutic threshold for the Css of FLV and probably also for the Css of FLA, and the Css of FLV+FLA above 180 ng/ml best predicts a good therapeutic response.

Topics: Adult; Aged; Amino Acids; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6; Depressive Disorder, Major; Dose-Response Relationship, Drug; Female; Fluvoxamine; Humans; Japan; Male; Middle Aged; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Smoking; Treatment Outcome

A double-blind, multinational study was conducted to compare the efficacy and safety of fluvoxamine and fluoxetine in outpatients with major depressive episode; 184 patients were randomised to fluvoxamine (100 mg/day) or fluoxetine (20 mg/day) for 6 weeks. Both drugs were effective and there were no statistically significant differences between them in the area under the curve of change from baseline in the Hamilton depression rating scale (HAMD) total score. However, the percentage of HAMD responders (>or= 50% decrease in HAMD total score) at week 2, the clinical global improvement severity of illness score at week 2 and the depression subscale of the irritability, depression and anxiety scale at weeks 1, 2 and 4, all showed significant advantages for fluvoxamine. During the last 2 weeks, fluvoxamine was significantly more effective in improving the HAMD sleep disturbance scale. Both drugs were well tolerated and there were no marked differences in their side effect profiles which were typical of SSRIs. Fluvoxamine and fluoxetine have similar efficacy and safety profiles in the treatment of major depressive episode; the findings of this study indicate that fluvoxamine may have a faster onset of action with respect to resolution of depressive symptoms and result in a better improvement in sleep quality.

Topics: Adolescent; Adult; Aged; Depressive Disorder, Major; Double-Blind Method; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors

We investigated the association between serotonergic polymorphisms and incidence of nausea, which is the most frequent side-effect of selective serotonin reuptake inhibiters (SSRIs), in 66 patients treated with fluvoxamine in a protocolized-dosing method. We focused on three polymorphisms of serotonin (5-HT) neuronal systems such as 5-HT transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR), a variable number of tandem repeat (VNTR) polymorphism in the second intron of the 5-HTT gene (STin2) and tryptophan hydroxylase (TPH) gene polymorphism in intron 7 (TPH-A218C), which have been reported to possess positive association with treatment response to SSRIs. In addition to this, the relationship between development of nausea and treatment response was also analyzed. Results suggested that these three polymorphisms did not affect the development of fluvoxamine-induced nausea, and that incidence of nausea was not a phenomenon that predicts the treatment response to fluvoxamine.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Carrier Proteins; Chi-Square Distribution; Depressive Disorder, Major; Female; Fluvoxamine; Gene Frequency; Genotype; Humans; Introns; Linkage Disequilibrium; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Minisatellite Repeats; Nausea; Nerve Tissue Proteins; Polymorphism, Genetic; Serotonin Plasma Membrane Transport Proteins; Tryptophan Hydroxylase

We investigated the relationships between the changes in plasma catecholamine metabolites obtained from depressed patients before and after administration of sulpiride, a benzamide compound, or fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), and between clinical responses to treatment with each of these drugs. Responders to sulpiride had significantly lower plasma homovanillic acid (pHVA) levels before administration of sulpiride than did non-responders or controls (responders: 4.5 +/- 3.1 ng/ml, non-responders: 11.1 +/- 5.9 ng/ml, controls: 10.9 +/- 5.3 ng/ml). Positive relationships were observed between changes in pHVA levels and improvement rates in the 17-item Hamilton Depression Rating Scale (Ham-D). In contrast, responders to fluvoxamine had significantly higher plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels before administration of fluvoxamine than did non-responders or controls (responders: 8.5 +/- 1.8 ng/ml, non-responders: 5.9 +/- 2.I ng/ml, controls: 5.2 +/- 2.9 ng/ml). Negative relationships were observed between changes in pMHPG levels and improvement rates in Ham-D. These results suggest that lower pretreatment pHVA levels and higher pretreatment levels of pMHPG might be predictors of response to sulpiride and fluvoxamine, respectively, and that sulpiride might produce a functional increase in the dopaminergic system, resulting in improvement in some depressive symptoms; fluvoxamine, on the other hand, might produce a functional decrease in the noradrenergic system via serotonergic neurons, resulting in improvement of those symptoms.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Biomarkers; Depressive Disorder, Major; Dopamine Antagonists; Female; Fluvoxamine; Homovanillic Acid; Humans; Male; Methoxyhydroxyphenylglycol; Middle Aged; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Sulpiride; Treatment Outcome

Genetic polymorphism of the serotonin 5-HT(2A) receptor seems to be associated with therapeutic response to selective serotonin reuptake inhibitors (SSRIs). The present study investigated whether a novel -1438G/A polymorphism in the promoter region of the 5-HT(2A )receptor gene is associated with therapeutic response to fluvoxamine (an SSRI) in 66 Japanese patients with major depressive disorder. Fluvoxamine (50 to 200 mg) was administered twice daily for 6 weeks. Fifty-four patients completed this study. The genotype distribution and the allele frequencies showed no significant difference between responders and non-responders. The time-course of the Montgomery-Asberg Depression Rating Scale scores showed no significant difference among -1438G/G, -1438G/A, and -1438A/A genotype groups. The results demonstrated that the -1438G/A promoter polymorphism in the 5-HT(2A) receptor gene was unlikely to have a major role in therapeutic response to fluvoxamine in Japanese patients with major depressive disorder.

Topics: Adult; Aged; Chi-Square Distribution; Depressive Disorder, Major; Dose-Response Relationship, Drug; Female; Fluvoxamine; Gene Frequency; Genotype; Humans; Japan; Male; Middle Aged; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Psychiatric Status Rating Scales; Receptor, Serotonin, 5-HT2A; Receptors, Serotonin; Selective Serotonin Reuptake Inhibitors; Time Factors; 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

Although increasing evidence suggests that selective serotonin reuptake inhibitor (SSRI) treatment may be effective for anxiety in addition to depression, SSRI anxiolysis has not been definitively related to the inhibition of serotonin (5-HT) transport. The gene that encodes for the human serotonin transporter (5-HTT) expresses its protein in neurons and in blood platelets, and both tissues respond to transport inhibition similarly in response to SSRI treatment. This study examined the relationship between the change in the 5-HTT's apparent affinity for 5-HT and the anxiolytic response in a group of 18 fluvoxamine-treated patients meeting Structured Clinical Interview for DSM-IV criteria for both generalized anxiety disorder and major depression. Significant decreases were found in both Hamilton anxiety and Hamilton depression scores over a 2-month treatment period. Robust increases were found in the apparent affinity constant (Km) for platelet 5-HT transport with treatment, and the increases covaried significantly with the decrease in anxiety (F = 4.97, p < 0.03). The pretreatment 5-HTT Km significantly correlated with the improvement in depression scores (r = 0.53, p < 0.03), consistent with the Hypothesis of Initial Conditions. These results suggest that the therapeutic effect of SSRI treatment can be linked to the magnitude and time-course of 5-HT transport inhibition effected with fluvoxamine, a drug that seems to have an antianxiety effect of the same magnitude as its effect on depression.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Anti-Anxiety Agents; Anxiety Disorders; Carrier Proteins; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Membrane Glycoproteins; Membrane Transport Proteins; Mental Status Schedule; Middle Aged; Nerve Tissue Proteins; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins; Treatment Outcome

The antidepressant efficacy and tolerability of milnacipran, a dual action serotonin-noradrenaline reuptake inhibitor, were compared with those of the selective serotonin reuptake inhibitor, fluvoxamine, in 113 patients with moderate to severe major depression. Treatment with milnacipran, 50 mg b.d. for 6 weeks, produced a significantly greater reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores than fluvoxamine, 100 mg b.d. (P = 0.007; 65.4% versus 49.9%, respectively); significantly greater decreases were also seen on days 7 (P = 0.04) and 28 (P = 0.03). The response rate (the proportion of patients showing a decrease in MADRS scores of at least 50%) was 78.9% in patients receiving milnacipran, compared with 60.7% in fluvoxamine-treated patients (P = 0.04). Milnacipran also produced greater improvements in 24-item Hamilton Depression Rating Scale scores (P = 0.05). On the Clinical Global Impression Improvement scale, 77.2% of milnacipran-treated patients were rated as considerably or markedly improved, compared with 60.7% of patients receiving fluvoxamine (P = 0.06 chi-squared). Both treatments were well tolerated; the only significant difference between the two groups was a higher incidence of tremor and drowsiness in patients treated with fluvoxamine. It is concluded that milnacipran may offer some advantages over selective serotonin reuptake inhibitors, such as fluvoxamine, in the treatment of moderate to severe major depression.

Topics: Adult; Aged; Antidepressive Agents; Cyclopropanes; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Middle Aged; Milnacipran; Treatment Outcome

It has been recently reported that the short variant of the serotonin transporter (5-HTT) gene-linked functional polymorphic region (5-HTTLPR) influences the antidepressant response to certain selective serotonin reuptake inhibitors. The aim of the present study was to test this finding in a sample of major and bipolar depressives, with or without psychotic features.. One hundred fifty-five 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. Allelic variation of 5-HTTLPR in each subject was determined using a polymerase chain reaction-based technique.. 5-HTTLPR short variant was associated with a poor response to fluvoxamine treatment, independently from the recorded clinical variables. More specifically, the diagnosis, the presence of psychotic features, and the severity of depressive symptomatology did not influence this association. Conversely, pindolol augmentation may ameliorate the rate of response in 5-HTTLPR short variant subjects, thus reducing the difference in the response rate among the genotype variants.. If confirmed, these results may improve patient care by helping the clinician to individualize treatment according to the patient's genetic 5-HTTLPR pattern.

Topics: Adult; Antidepressive Agents; Bipolar Disorder; Carrier Proteins; Delusions; Depressive Disorder, Major; Double-Blind Method; Drug Therapy, Combination; Female; Fluvoxamine; Genetic Variation; Genotype; Humans; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Pindolol; Polymorphism, Genetic; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins; Treatment Outcome

This study investigates the effect of chronic treatment with Fluvoxamine, a potent and specific serotonin reuptake sites inhibitor (SSRI), on 5HT(2) serotonin and D(2) dopamine receptors in the brain of drug naive unipolar depressed patients. Drug effect was evaluated in different cortical areas and in the basal ganglia by positron emission tomography (PET) and fluoro-ethyl-spiperone ([(18)F]FESP), an high affinity 5HT(2) serotonin and D(2) dopamine receptors antagonist. Patients underwent a PET study at recruitment and after clinical response to Fluvoxamine treatment. Nine of the 15 patients recruited completed the study. Fluvoxamine treatment significantly improved clinical symptoms and modified [(18)F]FESP binding in the frontal and occipital cortex of all of the nine patients who completed the study; in these regions a mean 31% increase in the in vivo [(18)F]FESP binding was found (P < 0.01). On the contrary, no significant changes in the in vivo [(18)F]FESP binding were found in the basal ganglia where [(18)F]FESP binds mainly to D(2) dopamine receptors. Chronic treatment with Fluvoxamine significantly increases the in vivo binding of [(18)F]FESP in the frontal and occipital cortex of drug naive unipolar depressed patients. The increase of the in vivo binding of [(18)F]FESP may reflect a modification in 5HT(2) binding capacity secondary to changes in cortical serotonin activity.

Topics: Adult; Antidepressive Agents, Second-Generation; Brain; Depressive Disorder, Major; Female; Fluorine Radioisotopes; Fluvoxamine; Humans; Male; Middle Aged; Selective Serotonin Reuptake Inhibitors; Spiperone; Tissue Distribution; Tomography, Emission-Computed

Topics: Adolescent; Adult; Aged; Cognitive Behavioral Therapy; Combined Modality Therapy; Depressive Disorder, Major; Family Practice; Female; Fluvoxamine; Humans; Male; Middle Aged; Paroxetine; Patient Care Team; Personality Inventory; Problem Solving; Treatment Outcome

This is a non-randomized exploratory study showing the sensitivity of neurophysiological parameters for autonomic side-effects during the application of antidepressant drugs. Inpatients on tricyclic antidepressants (TCA: amitriptyline or doxepine), inpatients on serotonine-reuptake inhibitors (SSRI: fluvoxamine or paroxetin) and a control group of healthy volunteers underwent neurophysiological examination. The treatment group was investigated after at least 7 days of continuous treatment with the final dose. Adjustment of the autonomic nervous system was studied, first, by measuring latency and amplitude of the sympathetic skin response (SSR), elicited by electric stimuli and by deep inspiration, and second, by analysis of the heart rate variation (HRV) during rest and inspiration. Relevant affections of the peripheral parts of the reflex arc under discussion were excluded by taking the nerve conduction velocity (NCV) and F-wave referring to cervical segment C7. In total, 48 individuals were examined. The TCA group showed delayed latencies and smaller amplitudes of the SSR in comparison with the controls. In the SSRI group, these parameters did not differ significantly from those of the controls. Analysis of HRV put further emphasis on the impaired adjustment of the autonomic nervous system in the TCA group. To sum up, our test battery indicated a specific vegetative alteration due to TCA.

Topics: Adult; Aged; Amitriptyline; Antidepressive Agents, Tricyclic; Autonomic Nervous System; Depressive Disorder, Major; Doxepin; Female; Fluvoxamine; Heart Rate; Humans; Male; Middle Aged; Neural Conduction; Paroxetine; Psychometrics; Reaction Time; Reflex; Selective Serotonin Reuptake Inhibitors

It has been reported that patients with major depressive disorder (MDD) are prone to developing ventricular arrhythmias. Moreover, the Sigma-1 receptor not only plays a crucial role in MDD but has also been shown to have antiarrhythmic properties. The Sigma-1 receptor is a common receptor related to depression and ventricular arrhythmias.. We analyzed the effects of the Sigma-1 receptor on depression and ventricular repolarization-related ion remodeling in MDD rats.. MDD was induced in rats by chronic unpredictable mild stress (CUMS), and 28 days later, the rats were subjected to behavior tests. Protein expression was measured by western blotting, and cardiac morphological changes were observed by Masson staining. Electrophysiological measurement of the myocardium was performed with the whole-cell patch-clamp technique.. Compared with the control rats, the MDD rats exhibited lower transient outward potassium current (Ito) and L-type calcium current (I. Taken together, our results indicate that Sigma-1 receptor modulates the functions of Ito and I

Topics: Action Potentials; Animals; Antidepressive Agents, Second-Generation; Arrhythmias, Cardiac; Behavior, Animal; Calcium Channels; Depressive Disorder, Major; Disease Models, Animal; Fluvoxamine; Heart Ventricles; Ligands; Male; Myocardium; Patch-Clamp Techniques; Potassium Channels; Rats; Receptors, sigma; Sigma-1 Receptor

Previous studies have shown that cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of fluvoxamine, the activity of which is highly dependent, inter alia, on the polymorphism of the gene encoding it. The objective of our study was to investigate the effect of 1846G>A polymorphism of the CYP2D6 gene on the efficacy and safety of fluvoxamine, using findings on CYP2D6 enzymatic activity and on CYP2D6 expression level in patients with depressive disorders comorbid with alcohol use disorder.. Efficacy and safety of fluvoxamine depend on the polymorphism of CYP2D6 gene in patients with major depressive disorder.. Our study enrolled 96 male patients with depressive disorders comorbid with alcohol use disorder. Patients were examined on days 1, 9, and 16 of fluvoxamine therapy.. Treatment efficacy was evaluated using the validated 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 CYP2D6 was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of given isoenzyme and its metabolite in urine (6-hydroxy-1,2,3,4-tetrahydro-β-carboline/pinoline ratio).. Our study revealed the statistically significant results for the treatment efficacy evaluation [the Hamilton Depression Rating Scale scores at the end of the treatment course: (GG) 2.0 (1.0-4.0) and (GA) 5.0 (4.0-7.0), P < 0.001]. Analysis of the results of the pharmacotranscriptomic part of the study did not show the statistically significant difference in the hsa-miR-370-3p plasma levels in patients with different genotypes: (GG) 26.9 (15.0-32.2), (GA) 31.8 (22.7-33.7), P = 0.247. In addition, we evaluated the relationship between the CYP2D6 enzymatic activity (as evaluated by 6-hydroxy-1,2,3,4-tetrahydro-β-carboline/pinoline ratio measurement) and the hsa-miR-370-3p plasma concentration: rs = -0.243, P = 0.017.. The effect of genetic polymorphism of the CYP2D6 gene on the efficacy and safety profiles of fluvoxamine was demonstrated in a group of 96 patients with depressive disorders comorbid with alcohol use disorder.

Topics: Cytochrome P-450 CYP2D6; Depressive Disorder, Major; Fluvoxamine; Genotype; Humans; Male; MicroRNAs; Polymorphism, Genetic; Tandem Mass Spectrometry

Topics: Antidepressive Agents; Anxiety; Citalopram; Depressive Disorder, Major; Fluoxetine; Fluvoxamine; Follow-Up Studies; Humans; Least-Squares Analysis; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

Glycogen synthase kinase-3β (GSK-3β) polymorphisms are known to influence hippocampal brain tissue volume in individuals with major depressive disorder (MDD). However, the effects of the GSK-3β gene single nucleotide polymorphisms (SNPs) in those receiving antidepressant therapy are unknown.. In the present study, we examined the relationship between brain volume-related SNPs of the GSK-3β gene and antidepressant treatment effects in patients with MDD.. Paroxetine, fluvoxamine, or milnacipran was administered to 143 Japanese patients with MDD. Two SNPs of the GSK-3β gene (rs6438552 and rs12630592) that influence brain volume in the hippocampus were genotyped. For the primary outcome, the relationship between genetic variations in the SNPs and the percent change in the Hamilton Rating Scale for Depression (HAM-D) score at week 6 was examined. In addition, rs334558, which has been reported repeatedly, was also genotyped.. There was a significant correlation between the two SNPs and the percent change in the HAM-D scores at week 6 (rs6438552 A/A vs. A/G + G/G: p = 0.016; rs12630592 G/G vs. G/T + T/T: p = 0.016). There was high linkage disequilibrium between the rs6438552 and rs12630592 SNPs. The correlation between high therapeutic response over time and the two SNPs were also confirmed (rs6438552 A/A vs. others: p = 0.031; rs12630592 G/G vs. others: p = 0.031).. Our results suggest that two GSK-3β variants that influence brain volume were associated with changes in the HAM-D scores at week 6 in patients with MDD.

Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Female; Fluvoxamine; Genetic Predisposition to Disease; Genotype; Glycogen Synthase Kinase 3 beta; Hippocampus; Humans; Linkage Disequilibrium; Male; Middle Aged; Paroxetine; Polymorphism, Single Nucleotide

Topics: Adult; Anti-Anxiety Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Anxiety Disorders; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Lamotrigine; Mirtazapine; Obsessive-Compulsive Disorder; Serotonin and Noradrenaline Reuptake Inhibitors; Tic Disorders; Venlafaxine Hydrochloride

There is insufficient serotonergic neuronal function in the pathophysiology of major depressive disorder (MDD). Serotonin transporter (SERT) plays a critical role in terminating the function of serotoninergic neurons. SERT is linked to vulnerability to MDD and is an important target for antidepressants. The expression of SERT in lymphocytes and platelets is associated with their expression in central nervous system. Most of the clinical studies that have analyzed the role of SERT in depression have focused on absolute expression of SERT in the brain or peripheral tissue. Our study has shown that the SERT protein is ubiquitinated, which has been implicated through the SERT stability and depressive behaviors in mice. In our study, we have used lymphoblasts derived from the peripheral blood lymphocytes to quantitatively examine SERT protein expression and ubiquitination in fluvoxamine-responsive and fluvoxamine-resistant MDD patients. We found that the protein levels of SERT were higher in the fluvoxamine-resistant MDD patients. Ubiquitinated protein levels of SERT were lower in the fluvoxamine-resistant MDD patients. The proteasome inhibitor failed to increase the protein levels of SERT in both fluvoxamine-responsive and fluvoxamine-resistant MDD patients. In sum, these findings suggest that the downregulation of the ubiquitination of SERT protein induces insufficient degradation of SERT by proteasome, which resulted in the upregulation of SERT protein in fluvoxamine-resistant MDD patients. Although further studies with various populations will be required to generalize results, SERT protein expression, ubiquitination, and the responsiveness of SERT expression to proteasome inhibitor are potential biomarkers for the diagnosis of MDD and antidepressant efficacy.

Topics: Adult; Antidepressive Agents; Cells, Cultured; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Leupeptins; Lymphocytes; Male; Middle Aged; Proteasome Inhibitors; Serotonin Plasma Membrane Transport Proteins; Treatment Failure; Ubiquitination; Young Adult

Dose equivalence of antidepressants is critically important for clinical practice and for research. There are several methods to define and calculate dose equivalence but for antidepressants, only daily defined dose and consensus methods have been applied to date. The purpose of the present study is to examine dose equivalence of antidepressants by a less arbitrary and more systematic method.. We used data from all randomized, double-blind, flexible-dose trials comparing fluoxetine or paroxetine as standard drugs with any other active antidepressants as monotherapy in the acute phase treatment of unipolar depression. We calculated the ratio of the mean doses for each study and weighted it by the total sample size to find the weighted mean ratio for each drug, which was then used to define the drug׳s dosage equivalent to fluoxetine 40mg/d.. We included 83 studies (14 131 participants). In the primary analysis, fluoxetine 40mg/day was equivalent to paroxetine dosage of 34.0mg/day, agomelatine 53.2mg/day, amitriptyline, 122.3mg/day, bupropion 348.5mg/day, clomipramine 116.1mg/day, desipramine 196.3mg/day, dothiepin 154.8mg/day, doxepin 140.1mg/day, escitalopram 18.0mg/day, fluvoxamine 143.3mg/day, imipramine 137.2mg/day, lofepramine 250.2mg/day, maprotiline 118.0mg/day, mianserin, 101.1mg/day, mirtazapine 50.9mg/day, moclobemide 575.2mg/day, nefazodone 535.2mg/day, nortriptyline 100.9mg/day, reboxetine 11.5mg/day, sertraline 98.5mg/day, trazodone 401.4mg/day, and venlafaxine 149.4mg/day. Sensitivity analyses corroborated the results except for doxepin.. The number of studies for some drugs was small. The current method assumes dose response relationship of antidepressants.. Our findings can be useful for clinicians when they switch antidepressants and for researchers when they compare various antidepressants in their research.

Topics: Adult; Amitriptyline; Antidepressive Agents; Bupropion; Citalopram; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Evidence-Based Medicine; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Moclobemide; Nortriptyline; Paroxetine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

We investigated the association between remission of depressive symptoms in fluvoxamine treatment and catechol-O-methyltransferase (COMT) gene. Sixteen SNPs in the COMT gene were investigated in 123 outpatients with major depression. Three single nucleotide polymorphisms located in the 5' region were associated with remission in fluvoxamine-treated outpatients with moderate to severe depression.

Topics: Antidepressive Agents, Second-Generation; Catechol O-Methyltransferase; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Middle Aged; Promoter Regions, Genetic; Treatment Outcome

Polymorphisms in the glucocorticoid receptors (GRs) have been widely studied with rather less emphasis on relating their differences with possible pharmacological treatment outcomes. The purpose of this study was to investigate whether Bcl1 polymorphisms of GRs are associated with the antidepressant effect of milnacipran, a serotonin noradrenaline reuptake inhibitor (SNRI), and fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), in Japanese patients with depression.. Patients were prescribed either milnacipran (n = 98) or fluvoxamine (n = 95). The severity of depression was assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) at 0, 1, 2, 4 and 6 weeks of treatment.. Both agents were similarly effective in reducing MADRS scores in 6 weeks. In all subjects receiving milnacipran or fluvoxamine, our data showed no significant interaction between Bcl1 polymorphisms and therapeutic effects. However, when milnacipran- and fluvoxamine-treated subjects were analyzed independently, patients with G allele in Bcl1 polymorphism had a significantly better response to fluvoxamine than those with C/C genotype. On the other hand, no significant relationship was found between treatment response to milnacipran and Bcl1 polymorphism.. Bcl1 polymorphism may be one of the genetic factors in predicting treatment response to SSRI but not SNRI in Japanese patients with depression.

Topics: Antidepressive Agents; Asian People; Cyclin D1; Cyclopropanes; Depressive Disorder, Major; Female; Fluvoxamine; Genotype; Humans; Male; Middle Aged; Milnacipran; Polymorphism, Single Nucleotide; Receptors, Glucocorticoid; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Treatment Outcome

There is growing evidence that individual differences among patients with major depressive disorder (MDD) on psychological and demographic measures may predict the therapeutic response to selective serotonin reuptake inhibitors (SSRIs). In this retrospective chart review, 108 outpatients with current major depressive episodes were treated with citalopram, paroxetine, or fluvoxamine. The Hamilton Depression Rating Scale and the Minnesota Multiphasic Personality Inventory-2 were administered before and after 8 weeks of SSRIs treatment. Clinical response was defined as a 50% or greater decrease in the 17-item Hamilton Depression Rating Scale total score (final visit minus baseline). This naturalistic short-term follow-up outcome study demonstrates that among depressive outpatients who responded to an 8-week trial, 57.4% achieved a good response to SSRIs. Statistical analysis showed that SSRI treatment may be 3.03 times more advantageous for MDD outpatients who are younger than 39 years. The patients with an elevated score of above 66T on the Social Introversion Minnesota Multiphasic Personality Inventory-2 scale are approximately 0.37 times as likely to be SSRI responders as are patients with a Social Introversion score less than 66T. Thus, it seems that in MDD outpatient age is the strongest predictor of response to SSRIs.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Ambulatory Care; Antidepressive Agents, Second-Generation; Chi-Square Distribution; Citalopram; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Israel; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Paroxetine; Patient Selection; Personality Assessment; Predictive Value of Tests; Psychiatric Status Rating Scales; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Time Factors; Treatment Outcome; Young Adult

Sexual dysfunction is a major side effect of selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs). We conducted a genome-wide association study to identify the genetic factors contributing to the risk of SSRI/SNRI-induced sexual dysfunction by testing 186 320 single nucleotide polymorphism (SNP) markers in a cohort of 201 Japanese major depression patients including 36 with sexual dysfunction induced by SSRI (paroxetine or fluvoxamine) or SNRI (milnacipran). The Cochran-Armitage trend test showed that 11 SNPs, tightly clustered in a distinct region on chromosome 14q21.3, were associated with SSRI/SNRI-induced sexual dysfunction at a genome-wide significance level after false discovery rate (FDR) correction, and the strongest SNP association was with rs1160351 (P=3.04 × 10(-7), risk ratio=2.92, 95% confidence interval (CI)=1.79-4.76). These SNPs mapped to the intronic region of the MDGA2 gene. A Manhattan plot showed that the strong association peak remained in MDGA2 after adjustment for sex and age in a multivariable logistic regression analysis although P values increased slightly and became non-significant. Replication studies with larger sample sizes are required to validate this exploratory study, but our findings may provide insights into the genetic basis of sexual dysfunction induced by SSRI/SNRI.

Topics: Adrenergic Uptake Inhibitors; Adult; Aged; Aged, 80 and over; Asian People; Cohort Studies; Cyclopropanes; Depressive Disorder, Major; Female; Fluvoxamine; Genome-Wide Association Study; Genotype; GPI-Linked Proteins; Humans; Male; Middle Aged; Milnacipran; Neural Cell Adhesion Molecules; Paroxetine; Polymorphism, Single Nucleotide; Selective Serotonin Reuptake Inhibitors; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological

Tetrahydrobiopterin (BH4) plays an important role in the biosynthesis of serotonin, melatonin and catecholamines, all of which are implicated in the pathophysiology of mood disorders (MDs), including major depressive disorder (MDD) and bipolar disorder (BP). Production of BH4 is regulated by GTP cyclohydrolase transcription and activity. Thus, we considered the GTP cyclohydrolase gene (GCH1) to be a good candidate gene in the pathophysiology of MDs and of the serotonin selective reuptake inhibitors (SSRIs) response in MDD, and conducted a case-control study utilizing three SNPs (rs8007267, rs3783641 and rs841) and moderate sample sizes (405 MDD patients, including 262 patients treated by SSRIs, 1022 BP patients and 1805 controls).. A multiple logistic regression analysis was carried out to compare the frequencies of each SNP genotype for the target phenotype across patients and controls in several genetic models, while adjusting for possible confounding factors. A clinical response was defined as a decrease of more than 50% from the baseline score on the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) within 8 weeks, and clinical remission as a SIGH-D score of less than 7 at 8 weeks.. No associations between three SNPs in GCH1 and MDD or BP were observed; however, GCH1 was associated with SSRI therapeutic response in MDD in all the marker's haplotype analysis (Global P value=0.0379).. Results suggest that GCH1 may predict response to SSRI in MDD in the Japanese population. Nevertheless, a replication study using larger samples may be required for conclusive results, since our sample size was small.

Topics: Adult; Antidepressive Agents; Asian People; Bipolar Disorder; Case-Control Studies; Depressive Disorder, Major; Female; Fluvoxamine; Gene Frequency; Genotype; GTP Cyclohydrolase; Haplotypes; Humans; Logistic Models; Male; Middle Aged; Phenotype; Polymorphism, Single Nucleotide; Selective Serotonin Reuptake Inhibitors

Several investigations have reported that abnormalities in circadian rhythms might be related to the pathophysiology of major depressive disorder (MDD) and the therapeutic response to selective serotonin reuptake inhibitors (SSRIs). Recently, ubiquitin-specific peptidase 46 (USP46), a new molecule related to the circadian clock system, has been described. We conducted a case control study between seven tagging SNPs (rs10517263, rs17675844, rs6554557, rs12646800, rs2244291, rs10034164, rs346005) in the USP46 gene, MDD, and the SSRI therapeutic response in MDD in the Japanese population.. We recruited 432 MDD patients (202 males and 230 females) and 792 healthy controls (319 males and 473 females). Two hundred sixty-one of 432 MDD patients were treated with SSRIs (fluvoxamine, sertraline or paroxetine).. We detected an association between the USP46 gene and MDD in a haplotype analysis (rs2244291-rs10034164-rs346005 and rs12646800-rs2244291-rs10034164-rs346005). However, we did not find any association between the USP46 gene and SSRI response or remission in MDD in the Japanese population.. A replication study using larger samples may be required for conclusive results, since our sample size was small.. Our results suggest that the USP46 gene might play a role in the pathophysiology of MDD in the Japanese population.

Topics: Adult; Asian People; Case-Control Studies; Circadian Clocks; Depressive Disorder, Major; Endopeptidases; Female; Fluvoxamine; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Male; Paroxetine; Polymorphism, Single Nucleotide; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome; Ubiquitin

Several investigations have reported that the translin-associated factor X gene (TSNAX)/disrupted-in-schizophrenia-1 gene (DISC1) was associated with major psychiatric disorders including schizophrenia, bipolar disorder (BP), and major depressive disorder (MDD). TSNAX is located immediately upstream of DISC1, and has been shown to undergo intergenic splicing with DISC1. It thus may also be influenced by translocation. To our knowledge, there are no reported gene-based association analyses between TSNAX and mood disorders in the Japanese population. We conducted a case-control study of Japanese samples (158 bipolar patients, 314 major depressive disorder patients, and 811 controls) with three tagging SNPs in TSNAX, selected using HapMap database. In addition, we performed an association analysis between TSNAX and the efficacy of fluvoxamine treatment in 120 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 rs766288 in TSNAX and female MDD in the allele/genotype analysis. However, we did not find any association between TSNAX and BP or the fluvoxamine therapeutic response in MDD in the allele/genotype analysis or haplotype analysis. Our results suggest that rs766288 in TSNAX may play a role in the pathophysiology of female MDD in the Japanese population. A replication study using larger samples may be required for conclusive results, since our sample size was small.

Topics: Adult; Antidepressive Agents, Second-Generation; Asian People; Case-Control Studies; Depressive Disorder, Major; DNA-Binding Proteins; Female; Fluvoxamine; Genetic Predisposition to Disease; Genotype; Haplotypes; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Psychiatric Status Rating Scales; Young Adult

Several recent investigations reported that the serotonin 2A receptor gene (HTR2A) was associated with selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder. There have also been two reported association analyses of HTR2A with SSRI response in Japanese MDD patients, but the results were rather inconsistent and both studies had the problem of small sample sizes. Therefore, we conducted a replication association study using a sample larger than those in the two original Japanese studies (265 MDD patients), and found that four SNPs, two functional SNPs (-A1438G: rs6311 and T102C: rs6313) and two SNPs (rs7997012 and rs1928040) in HTR2A, were associated with the therapeutic response to SSRIs. HTR2A was associated with the therapeutic response SSRIs in Japanese MDD patients in a haplotype-wise analysis (P(all markers) = 0.0136), and a significant association between rs1928040 in HTR2A and SSRI response was detected in MDD (P(allele-wise analysis) = 0.0252). However, this significance disappeared after Bonferroni correction (P(allele-wise analysis) = 0.101). In conclusion, we suggest that HTR2A may play an important role in the pathophysiology of the therapeutic response to SSRIs in Japanese MDD patients. However, it will be important to replicate and confirm these findings in other independent studies using large samples.

Topics: Asian People; Depressive Disorder, Major; Fluvoxamine; Genotype; Haplotypes; Humans; Linkage Disequilibrium; Paroxetine; Polymorphism, Single Nucleotide; Receptor, Serotonin, 5-HT2A; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome

Nitric oxide has been reported to play a role in neural transmitter release and N-methyl-D-aspartate receptor activation, as well as to be related to oxidative stress. Abnormalities in both of these mechanisms are thought to be involved in the pathophysiology of mood disorders including major depressive disorder (MDD) and bipolar disorder (BP). In addition, several lines of evidence support an association between abnormalities in neuronal nitric oxide synthases (nNOS) and mood disorders. Therefore, we studied the association of nNOS gene (NOS1) and mood disorders and the efficacy of fluvoxamine treatment in Japanese MDD patients.. Using a single nucleotide polymorphism (SNP; rs41279104, also called ex1c), we conducted a genetic association analysis of case-control samples (325 MDD patients, 154 BP patients and 807 controls) in the Japanese population. In addition, we performed an association analysis between NOS1 and the efficacy of fluvoxamine treatment in 117 MDD patients. We defined a clinical response as a decrease of more than 50% in baseline SIGH-D (Structured Interview Guide for the Hamilton Rating Scale for Depression) score within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks.. We did not detect a significant association between NOS1 and MDD, BP or the fluvoxamine therapeutic response in MDD in allele/genotype-wise analysis.. We did not detect an association between only one marker (rs41279104) in NOS1 and Japanese mood disorder patients and fluvoxamine response, but sample sizes were probably too small to allow a meaningful test. Moreover, because we did not perform an association analysis based on linkage disequilibrium and a mutation scan of NOS1, a replication of the study using a larger sample and based on linkage disequilibrium may be required for conclusive results.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Chi-Square Distribution; Depressive Disorder, Major; Female; Fluvoxamine; Gene Frequency; Genome-Wide Association Study; Genotype; Humans; Japan; Male; Middle Aged; Nitric Oxide Synthase Type I; Pharmacogenetics; Polymorphism, Single Nucleotide

Several investigations have suggested the possible involvement of sigma 1 non-opioid intracellular receptor 1 (sigma 1 receptor) in the pathophysiology of major depressive disorder (MDD). Sigma 1 receptors are also one of the major pharmacological therapeutic targets of selective serotonin reuptake inhibitors (SSRIs). To evaluate the association of sigma 1 receptor gene (SIGMAR1) and MDD and SSRIs therapeutic response in MDD, we conducted a case-control study of Japanese samples (466 MDD patients, 516 controls and 208 MDD patients treated by fluvoxamine or sertraline).. We defined a clinical response as a decrease of more than 50% in baseline the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) within 8 weeks, and clinical remission as an SIGH-D score of less than 7 at 8 weeks. Therefore, we selected rs1800866 in SIGMAR1 for the following association analysis.. In the logistic regression analysis, we detected an association of the phenotypes (MDD or controls) with rs1800866 genotype. However, we did not detect an association between rs1800866 and SSRI therapeutic response in Japanese MDD. In addition, remission with SSRI was not associated with rs1800866. Also, we did not detect a novel polymorphism in SIGMAR1 when we performed a mutation search using MDD treated by SSRIs samples.. Our results suggest that rs1800866 in SIGMAR1 may play a role in the pathophysiology of MDD in the Japanese population. Also, SIGMAR1 does not play a role in the therapeutic response to SSRI in Japanese MDD patients. However, because our sample was small, a replication study using another population and larger sample will be required for conclusive results.

Topics: Adult; Case-Control Studies; Depressive Disorder, Major; Female; Fluvoxamine; Genetic Association Studies; Genotype; Humans; Japan; Logistic Models; Male; Middle Aged; Phenotype; Polymorphism, Single Nucleotide; Psychiatric Status Rating Scales; Receptors, sigma; Remission Induction; Selective Serotonin Reuptake Inhibitors; Sertraline; Sigma-1 Receptor; Time Factors; Treatment Outcome

Selective serotonin reuptake inhibitors (SSRIs) are first line drugs for treating not only depressive disorder but also anxiety disorder. Fluvoxamine, a SSRI, is mainly metabolized by cytochrome P450 (CYP) 2D6 and 1A2. However, paroxetine, an another SSRI is potent inhibitor for CYP 2D6. We report a case with depression whose plasma fluvoxamine level rapidly increased after the addition of paroxetine while switching from fluvoxamine to paroxetine. The case indicates that emerging adverse effects via the pharmacokinetic interaction of these drugs when switching patients from fluvoxamine to paroxetine can occur.

Topics: Adult; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Depressive Disorder, Major; Drug Interactions; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Paroxetine

Topics: Accidental Falls; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Delirium; Depressive Disorder, Major; Diclofenac; Drug Interactions; Female; Fluid Therapy; Fluvoxamine; Follow-Up Studies; Haloperidol; Humans; Lithium Carbonate; Pain

Recent studies have shown that selective serotonin reuptake inhibitors (SSRIs) have circadian properties, suggesting that the antidepressive action of SSRIs may also be attributable to circadian mechanisms. Another study reported an association between clock gene (CLOCK) and improvements in insomnia symptoms from SSRIs treatment. Therefore, we examined the association between CLOCK and the efficacy of fluvoxamine treatment in 121 patients with Japanese major depressive disorder (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 therapeutic response as a decrease of more than a 50% in baseline SIGH-D within 8 weeks, and clinical remission as a SIGH-D score of less than seven at 8 weeks. We selected three tagging SNPs in CLOCK for the subsequent statistical association analysis. We detected a significant association between rs3736544, a synonymous polymorphism in exon 20, and the fluvoxamine therapeutic response in MDD in the allele/genotype-wise analyses. In addition, remission with fluvoxamine was also significantly associated with rs3736544. These associations remained significant after Bonferroni correction. Moreover, haplotype analysis findings supported these significant associations, which appeared to be due mainly to rs3736544, in the fluvoxamine therapeutic remission. Our results indicate that CLOCK genotype may be a predictor of fluvoxamine treatment response in Japanese MDD. However, our sample size was small, and a replication study using larger samples may be required for conclusive results.

Topics: Adult; Asian People; Biological Clocks; Circadian Rhythm; CLOCK Proteins; Depressive Disorder, Major; Female; Fluvoxamine; Genetic Variation; Genotype; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Trans-Activators; Treatment Outcome

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

Sleep-wake disturbance, frequently observed in major depressive disorder (MDD), negatively influences clinical status. Treatment with antidepressants also reportedly affects circadian rhythms. In a recent in vitro study, the nuclear receptor Rev-erbalpha was reported to be related to circadian rhythms, and was shown to be involved in the biological action of lithium therapy. Therefore, we examined the association between the orphan nuclear receptor Rev-erbalpha gene (NR1D1) and the efficacy of fluvoxamine treatment in 118 Japanese patients with major depressive disorder.. The scores of the MDD patients in this study on the 17 items of the Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-D) were 12 or higher. We defined a clinical response as a decrease of more than 50% in baseline SIGH-D within 8 weeks and clinical remission as a SIGH-D score of less than 7 at 8 weeks. We selected 3 'tagging SNPs' in NR1D1 for the following association analysis.. We did not detect a significant association between NR1D1 and the fluvoxamine therapeutic response in MDD in allele/genotype-wise analysis or haplotype-wise analysis.. Our results suggest that NR1D1 does not play a major role in the therapeutic response to fluvoxamine in Japanese MDD patients. However, because our sample was small, a replication study using another population and a larger sample will be required for conclusive results.

Topics: Adult; Antidepressive Agents, Second-Generation; Depressive Disorder, Major; Female; Fluvoxamine; Gene Frequency; Genotype; Haplotypes; Humans; Japan; Linkage Disequilibrium; Male; Middle Aged; Nuclear Receptor Subfamily 1, Group D, Member 1; Polymorphism, Single Nucleotide; Receptors, Cytoplasmic and Nuclear; Remission Induction; Sequence Analysis, DNA; Severity of Illness Index; Treatment Outcome

Fluvoxamine, a selective serotonin reuptake inhibitor, is widely used to treat major depression. However, the symptomatological predictors of the response to fluvoxamine have not been studied.. This study included 100 Japanese patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for the diagnosis of major depressive disorders and whose score on the Montgomery and Asberg Depression Rating Scale (MADRS) was 21 or higher. Eighty-one patients were included. Patients with a pretreatment MADRS score of >or=31 were defined as 'severe' (n = 32) and the rest were defined as 'non-severe' (n = 49). The three-factor model of MADRS was used for analysis: the first factor was defined by three items, the second factor was defined by four items, and the third factor was defined by three items representing dysphoria, retardation, and vegetative symptoms, respectively. Fluvoxamine (100-200 mg/day) was administered twice daily for 6 weeks.. In the non-severe patients, the mean factor 3 score of the non-responders at pretreatment was significantly higher than that of the responders. However, a significant difference was observed in the mean factor 3 scores from 1 week onwards between the non-severe responders and non-responders. Furthermore, the fluvoxamine response rate in the severe patients was 75% and higher than that of the non-severe patients (65.3%).. This study suggested that a low factor 3 score at pretreatment was a good predictor of the response to fluvoxamine in non-severe patients. The marked efficacy of fluvoxamine in the treatment of severe patients was also confirmed.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Middle Aged; Personality Inventory; Prognosis; Psychometrics; Reproducibility of Results

Patient satisfaction with antidepressants (ADs) depends on various factors whose individual contributions are incompletely understood.. An online survey was conducted of 1199 Japanese individuals being treated for major depressive disorder. Satisfaction for each AD was quantified using a 5-point scale. The average of all agents was calculated for each subject and defined as the Satisfaction Score (SS). Those on a single AD medication (n=667) were divided into four subgroups based on their medication: fluvoxamine (n=165), milnacipran (n=91), paroxetine (n=196), and tricyclic antidepressant (TCA; n=103). Among those with higher SS (>or==4.0), their satisfaction reasons were elicited by three multiple-choice responses: efficacy, fewer side effects, and lower dosing frequency. To compare the responses to these three questions among the four subgroups, one-way analysis of variance and post-hoc comparison tests were performed. Logistic regression was done to determine whether these three responses predict higher satisfaction.. The number of ADs taken by an individual was negatively correlated with the SS (r=-.074, p=.011). SS did not correlate with demographic features. SS was similar among the four subgroups but their satisfaction reasons differed. Predictors of higher SS (SS=5.0 versus 4.0) were reporting "efficacy" and "fewer side effects" as satisfaction reasons.. Web-based surveys have a selection bias, and diagnoses were based on self-reports.. SS waned as the number of ADs increased. Among users of four ADs, SS was similar but their satisfaction reasons differed. Perceived efficacy and fewer side effects predicted higher drug satisfaction.

Topics: Analysis of Variance; Antidepressive Agents; Antidepressive Agents, Tricyclic; Cyclopropanes; Data Collection; Depressive Disorder, Major; Fluvoxamine; Humans; Internet; Japan; Logistic Models; Milnacipran; Paroxetine; Patient Satisfaction; Selective Serotonin Reuptake Inhibitors; Surveys and Questionnaires

The G-protein beta3 subunit (GNB3) gene is a key modulator of signal transduction and is a major candidate for SSRIs response. The aim of the present study is to test a possible effect of the C825T polymorphism on the antidepressant response and intolerance to selective serotonin reuptake inhibitors (SSRIs) in 146 Japanese samples with major depression treated with paroxetine or fluvoxamine for 6 weeks. The severity of depression symptom was assessed using the 21-item Hamilton Rating Scale for Depression (HAM-D) and adverse drug reactions were evaluated bi-weekly. No association with SSRIs treatment response was observed in 107 completers also including HAM-D baseline scores, SSRI type or/and 5-HTTLPR variants in the model as covariates. Furthermore, no significant association could be observed with intolerance to SSRIs in the whole subjects. The result suggests that C825T variants of GNB3 cannot play a major role as a predictor of treatment response as well as intolerance to SSRIs in Japanese patients with major depression.

Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Female; Fluvoxamine; Genotype; Heterotrimeric GTP-Binding Proteins; Humans; Japan; Male; Middle Aged; Paroxetine; Polymorphism, Genetic; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors

The aim of this study was to examine the effects of negative cognition on PBI score before and after treatment for depression. Forty major depressive disorder outpatients were assessed with the PBI scale and Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D) at the time of the first medical examination (baseline) and 8 weeks later. The SIGH-D scores decreased by about 50% from baseline to 8 weeks, but there was no significant change in the PBI scores of the depressed outpatients from baseline to 8 weeks. Analysis of covariance with the SIGH-D scores as covariate was conducted for PBI scores between baseline and 8 weeks to remove effects of MDD. No significant differences were found on any of the PBI scales. Even though the therapeutic values on the SIGH-D of the depressed patients indicated that depressive symptoms were reduced by about 50%, depression level did not influence the PBI scores. This study provides evidence for the stability of parental representations throughout treatment, as measured by the PBI.

Topics: Adult; Child; Cognition; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Object Attachment; Parent-Child Relations; Selective Serotonin Reuptake Inhibitors; Social Perception; Surveys and Questionnaires

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

Artificial neural networks (ANN) represent a promising tool for combining multiple predictors in complex diseases. Antidepressant response in mood disorders is a typical complex phenomenon were a number of predictors influence outcome under non-linear interactions. In the present study we tested a neural network strategy for antidepressant outcome in subjects affected by major depression. One hundred and forty-five never reported depressed inpatients were included in this study (major depressives/bipolars: 111/34). A multi layer perceptron network composed of 1 hidden layer with 13 nodes was chosen. The network was performed on the sample of 145 cases divided as follows: train 73+verify 36+test 36. Correlation of predicted versus observed response was 0.46 in the test (independent) sample that corresponds to 21% of variance explained. Number of episodes, side effects, delusional features, baseline HAM-D, length of current episode, lithium augmentation, current medical condition and personality disorders were the main factors identified by the model. Sex, age at onset, polarity, plasma level and baseline VAS score were part of the model but with a lower rank. Overall, our findings suggest that neural networks could be a valid technique for the analysis of psychopharmacology studies. The complex interactions modelled through ANN may be eventually applied at the clinical level for the individualized therapy.

Topics: Antipsychotic Agents; Bipolar Disorder; Delusions; Demography; Depressive Disorder, Major; Dose-Response Relationship, Drug; Female; Fluvoxamine; Humans; Incidence; Lithium Carbonate; Male; Middle Aged; Nerve Net; Personality Disorders; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Topics: Aged; Depressive Disorder, Major; Fluvoxamine; Humans; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors

It is often stated that depressive phenomenology and prognosis differ between elderly and younger depressed patients, in the direction of more severe symptoms and a poorer outcome in elderly individuals. However, studies addressing the topic remain largely inconclusive, and it has been suggested that potential biases connected with age may have confounded previous assessments. In this work we evaluated a sample of 93 elderly depressed individuals (>60 years) and 186 younger patients. All patients were assessed with the 21-item Hamilton Depression Rating Scale at intake and prospectively followed for 6 weeks during treatment with antidepressants. A number of clinical and demographic features were taken into account to investigate depressive phenomenology and outcome in late-life depression. We found that the high likelihood of medical disorders in elderly patients explained the more severe depressive symptomatology observed in this population. However, independently from physical problems, recovery was slightly slower in elderly compared with younger individuals. Finally, patients who developed their first lifetime episode late in life (>60 years) showed a form of symptomatology similar to that in elderly patients with an earlier onset, but they showed a more positive outcome. In conclusion, the present work suggests that depression in old age is similar to depression in other ages, except for a slightly slower response to pharmacotherapy. Minor health problems increase the severity of depression, but they do not interfere crucially with the efficacy of antidepressant treatment. Finally, late-onset depression is associated with a positive outcome.

Topics: Adult; Age Factors; Aged; Antidepressive Agents; Anxiety Disorders; Bipolar Disorder; Cyclohexanols; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Middle Aged; Paroxetine; Personality Inventory; Sertraline; Treatment Outcome; Venlafaxine Hydrochloride

Predicting the outcome of antidepressant treatment by pre-treatment features would be of great usefulness for clinicians as up to 50% of major depressives may not have a satisfactory response in spite of adequate trials of antidepressant drugs. In the present article we compared a linear multivariate model of predictors with a few artificial neural network (ANN) models differing from one another by outcome definition and validation procedure. The sample consisted of a reanalysis of 116 inpatients with a major depressive episode included in a 6-week open-label trial with fluvoxamine. With the original outcome definition (responders/non-responders), ANN performed better than logistic regression (90% of correct classifications in the training sample vs. 77%). However only 62% of new patients were correctly predicted by ANN for their outcome class. Length of the index episode, psychotic features and suicidal behavior emerged as outcome predictors in both models, while demographic characteristics, personality disorders and concomitant somatic morbidity were pointed to only by ANN analysis. Increase of classes in the outcome field resulted in a more elevated error: 46.4% for three classes, 60.4% for four classes and 70.3% for five classes. Overall, our findings suggest that antidepressant outcome prediction based on clinical variables is poor. The ANN approach is as valid as traditional multivariate techniques for the analysis of psychopharmacology studies. The complex interactions modelled through ANN may eventually be applied at the clinical level for individualized therapy. However, the accuracy of prediction is still far from satisfactory from a clinical point of view.

Topics: Adult; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Neural Networks, Computer; Prospective Studies; Selective Serotonin Reuptake Inhibitors

Topics: Aged; Depressive Disorder, Major; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Raloxifene Hydrochloride; Remission Induction; Selective Estrogen Receptor Modulators; Selective Serotonin Reuptake Inhibitors

Gender differences in the treatment response to fluvoxamine (selective serotonin re-uptake inhibitor) and milnacipran (serotonin/norepinephrine re-uptake inhibitor) were investigated in Japanese major depressive patients. A total of 125 Japanese patients was included in the present study. Sixty-six patients received fluvoxamine treatment. The daily dose was 50 mg/day for the first week and increased to 100 mg after 1 week, up to 200 mg after another week. Fifty-nine patients were given milnacipran. The daily dose was 50 mg/day for the first week, and up to 100 mg/day thereafter. Patients were divided into three groups: younger women (<44 years of age), older women (> or =44 years of age) and men. Depressive symptoms were evaluated using the Montgomery and Asberg Depression Rating Scale (MADRS) before treatment and at 1, 2, 4 and 6 weeks after the beginning of the study. In comparison with other groups, younger women treated with fluvoxamine demonstrated a significant difference in the time course of MADRS score change. However, these gender/age-related differences of antidepressant response were not observed in the patients treated with milnacipran. The results suggest that fluvoxamine is more effective in younger female patients than older female patients and male patients, while milnacipran is generally effective irrespective of gender or age.

Topics: Aging; Antidepressive Agents, Second-Generation; Cyclopropanes; Data Collection; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Japan; Male; Menopause; Middle Aged; Milnacipran; Psychiatric Status Rating Scales; Sex Characteristics

There is convincing evidence of interactions between serotonergic and dopaminergic systems and it seems that an increase of dopamine concentration in the whole brain could be a limiting factor for the antidepressant like effect of antidepressants. The COMT gene might be a good candidate for explaining some aspects of the pharmacological response to SSRIs.. The aim of our study was to analyse the Val 158 Met functional polymorphism on COMT gene and clinical response (4 weeks) and clinical remission (6/8 and 12 weeks) in two samples of depressive patients (DSM-IV) treated with SSRIs of Italian and Spanish origin. Clinical outcome was measured using 21 items Hamilton scale, weekly in the Italian sample (along 6 weeks) and monthly in the Spanish one (along 12 weeks).. No overall effect of genotype or genotypextime interaction was detected. However, we observed a genotypextime interaction on HDRS decrease for citalopram treatment (F((4.6,317.5)) = 3.38, P = 0.007) in the Spanish sample. No clear effect was observed in the Italian sample. The three samples were pooled in order to test if carrying the Met/Met genotype confers an increased risk for non-remission at 6-8 weeks. The results showed that Met/Met carriers have an odds ratio of 2.21 (95% CI [1.20-4.12]) for non-remission (chi(2) = 7.43, df = 2, P = 0.006). The Met/Met effect was not observed in response at 4th week (for all SSRI treatments) or in remission at 12th week (citalopram treatment).. COMT gene could have a small and indirect effect of clinical response to SSRIs by slowing-down the antidepressant action along the follow-up, basically in citalopram treatment.

Topics: Antidepressive Agents, Second-Generation; Biological Availability; Catechol O-Methyltransferase; Citalopram; Depressive Disorder, Major; Dopamine; Ethnicity; Female; Fluvoxamine; Follow-Up Studies; Frontal Lobe; Genetic Carrier Screening; Genotype; Humans; Male; Methionine; Paroxetine; Personality Inventory; Polymorphism, Genetic; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Valine

Recently, tricyclic antidepressants (TCAs) have been used mainly for treatment-resistant depression (TRD) because of their significant side effects . We report a patient whose prolonged depressive symptoms dramatically improved after the cessation of TCAs. TCAs may cause deterioration of depressive symptoms due to their neurotoxicity.

Topics: Adult; Antidepressive Agents, Tricyclic; Cabergoline; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Ergolines; Female; Fluvoxamine; Humans; Imipramine; Substance Withdrawal Syndrome; Treatment Outcome

Several studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) elicits moderate antidepressant effects. Several previous studies suggested that the dopaminergic system might be related to this therapeutic action of rTMS. We attempted to determine the effects of chronic rTMS on central dopaminergic function in depression using positron emission tomography (PET) with [11C]raclopride.. Nine patients with depression were treated with 10 daily sessions of rTMS (10 Hz, 5 s train, 20 trains at 100% motor threshold per session) over the left dorsolateral prefrontal cortex (DLPFC). Each patient underwent two [11C]raclopride PET scans and neuropsychological tests - before rTMS and 1 day after rTMS.. In five patients, the Hamilton Rating Scale for Depression (HRSD) significantly decreased. Patients showed significant improvement in verbal memory following rTMS. There were no changes in [11C]raclopride binding in the caudate nucleus and putamen after rTMS treatment.. Our sample size was limited, and our study was an open trial lacking sham-treated controls.. This study suggests that rTMS may be effective for the treatment of depression and also may improve verbal memory function. We observed no changes in [11C]raclopride binding, suggesting that there was no measurable increase in the release of dopamine at the second PET scan. Several animal studies and healthy human studies have indicated that dopamine can be released soon after acute rTMS. Our results suggest that release of striatal dopamine induced by rTMS may be only transient, or that dopamine release may be attenuated following chronic rTMS.

Topics: Adult; Antidepressive Agents, Second-Generation; Cognition; Depressive Disorder, Major; Dopamine; Dopamine Antagonists; Female; Fluvoxamine; Humans; Male; Neuropsychological Tests; Positron-Emission Tomography; Raclopride; Severity of Illness Index; Transcranial Magnetic Stimulation

Topics: Aged, 80 and over; Amnesia; Antidepressive Agents, Second-Generation; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Drug Therapy, Combination; Female; Fluvoxamine; Hallucinations; Humans; Hypnotics and Sedatives; Pyridines; Zolpidem

To present a case of improvement of paroxetine-induced dry mouth by substitution of fluvoxamine and analyze this case based on receptor occupancy theory.. A 66-year-old woman with major depressive disorder had been treated with brotizolam 0.5 mg/day, flunitrazepam 2 mg/day, sulpiride 100 mg/day, bromazepam 2 mg/day, trazodone 25 mg/day, and paroxetine hydrochloride 10 mg/day. Although her psychological symptoms improved gradually, she complained of dry mouth. Paroxetine was replaced with fluvoxamine maleate 50 mg/day, and the dryness disappeared within a month.. We calculated the time courses of muscarinic acetylcholine (mACh) receptor occupancy after oral administration of paroxetine and fluvoxamine at the treatment doses by using pharmacokinetic parameters obtained from the literature. The mACh receptor occupancy was estimated to be decreased from 0.22% to 0.020% by replacing paroxetine with fluvoxamine.. The improvement of dry mouth observed after the replacement of paroxetine with fluvoxamine in this patient may have been due to a decrease in the mACh receptor occupancy.

Topics: Aged; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Paroxetine; Receptors, Muscarinic; Selective Serotonin Reuptake Inhibitors; Xerostomia

The effect of amitriptyline on hypothalamic-pituitary-adrenocortical (HPA) axis activity was compared with that of fluvoxamine in 38 patients suffering from DMS-IV major depressive disorder. Basal plasma adrenocorticotropic hormone and cortisol levels were determined in the so-called "observation window" of an hour (08:00-09:00 h), and cortisol levels were determined again at 20:00 h. Clinical and biochemical assessments were performed before therapy (T0), at day 14 (T14), and at day 42 (T42) of the course of antidepressant treatment. At T0, neuroendocrine parameters did not differ in patients from those in controls, except for the ratio between cortisol levels at 20:00 h and the mean level of the "window" (ratio F20/F8), which was significantly higher, suggesting a dysregulation of the circadian pattern of cortisol. Although a decrease in the ratio F20/F8 was already apparent at T14 of both treatments, the repeated measures analysis of variance failed to demonstrate a significant variation with time (T0, T14, and T42) and with treatment (amitriptyline and fluvoxamine) for any hormonal measure. At T42, both treated groups showed a similar level of clinical improvement. Our results did not demonstrate any effect of antidepressant therapy on the cortisol circadian rhythm abnormality.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Amitriptyline; Circadian Rhythm; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Female; Fluvoxamine; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Schizophrenia; Selective Serotonin Reuptake Inhibitors

Topics: Antipsychotic Agents; Depressive Disorder, Major; Dibenzothiazepines; Drug Therapy, Combination; Fluvoxamine; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors

Topics: Adult; Antidepressive Agents, Second-Generation; Depressive Disorder, Major; Disorders of Excessive Somnolence; Drug Therapy, Combination; Fluvoxamine; Humans; Lithium; Male

This study compared the stabilized duloxetine dose through approximately 12 weeks of treatment in patients initiating duloxetine therapy with that in patients switching to duloxetine from selective serotonin reuptake inhibitors or venlafaxine. All patients met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depressive disorder. Patients (n = 112) exhibiting suboptimal response or poor tolerability to their current antidepressant medication (citalopram, escitalopram, fluvoxamine, paroxetine, sertraline, or venlafaxine) were switched to duloxetine 60 mg once daily (QD) without intermediate tapering or titration ("switching" group). A comparator group (n = 137), comprising patients not currently receiving antidepressant medication, was randomized to receive duloxetine 30 or 60 mg QD ("initiating" group). At the end of week 1, patients receiving 30 mg QD had their dose increased to 60 mg QD. During the remainder of the study, each patient's duloxetine dose could be titrated on the basis of degree of response within a range from 60 to 120 mg QD, with 90 mg QD as an intermediate dose. At the study end point, approximately one third of the patients in each treatment group were stabilized at each of the 3 studied duloxetine doses (60, 90, and 120 mg QD), and the distribution of stabilized doses among patients initiating duloxetine therapy did not differ significantly from that observed in patients switching to duloxetine. The efficacy of duloxetine in patients switching from selective serotonin reuptake inhibitor/venlafaxine did not differ significantly from that observed in untreated patients initiating duloxetine therapy (baseline-to-end point mean changes: 17-Item Hamilton Rating Scale for Depression total score, -13.1 vs. -13.5; Hamilton Rating Scale for Anxiety, -10.6 vs. -10.3; and Clinical Global Impression of Severity, -2.22 vs. -2.38, respectively). The rate of discontinuation caused by adverse events among patients switched to duloxetine was significantly lower than that in patients initiating duloxetine therapy (6.3% vs. 16.1%, P = 0.018). Treatment-emergent adverse events occurring in more than 10% of patients in both treatment groups were nausea, headache, dry mouth, insomnia, diarrhea, and constipation. In the first week of therapy, patients switched to duloxetine reported significantly lower rates of headache and fatigue compared with patients initiating duloxetine. Thus, the efficacy of duloxetine in switch

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents; Citalopram; Cyclohexanols; Depressive Disorder, Major; Dose-Response Relationship, Drug; Duloxetine Hydrochloride; Female; Fluvoxamine; Humans; Male; Middle Aged; Paroxetine; Sertraline; Thiophenes; Treatment Outcome; Venlafaxine Hydrochloride

Topics: Antipsychotic Agents; Citalopram; Delayed-Action Preparations; Depressive Disorder, Major; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Injections, Intramuscular; Middle Aged; Psychotic Disorders; Risperidone

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Dibenzothiazepines; Female; Fluvoxamine; Humans; Olanzapine; Quetiapine Fumarate; Weight Gain

Fluorine magnetic resonance spectroscopy (19F MRS), spectroscopic imaging (MRSI) and proton anatomical magnetic resonance imaging (1H MRI) were performed on brains and lower extremities of six subjects in vivo concurrently with HPLC of serum to investigate tissue and plasma drug localization and withdrawal kinetics in humans treated with fluvoxamine or fluoxetine. 19F MRS signal was unexpectedly detected in the lower extremities months after complete disappearance of signal from plasma and brain. MRSI suggested that the lower extremity fluvoxamine signal originated mainly from bone marrow. Results suggest long-term sequestration of these drugs or their metabolites mainly in bone marrow and possibly in surrounding tissue and demonstrate the usefulness of MRS to reveal drug-trapping compartments in the body.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Bone Marrow; Brain; Chromatography, High Pressure Liquid; Depressive Disorder, Major; Female; Fluorine Radioisotopes; Fluoxetine; Fluvoxamine; Humans; Hydrogen-Ion Concentration; Kinetics; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Protons; Selective Serotonin Reuptake Inhibitors; Time Factors

The purpose of this retrospective analysis was to estimate the cost and effectiveness of venlafaxine extended-release (VXR) compared with selective serotonin reuptake inhibitors in the outpatient treatment of major depressive disorder.. Pooled data from 8, 8-week, randomized, double-blind studies comparing treatment of major depressive disorder with venlafaxine/venlafaxine XR (n = 851), selective serotonin reuptake inhibitors (fluoxetine, paroxetine, fluvoxamine; n = 748), or placebo (4 studies; n = 446) were retrospectively analyzed to determine the economic implications of symptom remission from the perspective of a US third party payer and that of an employer. A decision modeling approach was used to determine cost and effectiveness ratios.. Patients on VXR were associated with 22.8 depression-free days versus 18.6 depression-free days with the studied selective serotonin reuptake inhibitors, based on the decision model. Productive and quality-adjusted days were also expected to increase for VXR patients (22.06 vs. 19.34 and 4.56 to 9.36 vs. 3.72 to 7.63), as was the percentage of patients achieving full activity (25.9% vs. 19.6%). The expected cost per patient achieving remission of symptoms was US 1303.94 dollars and US 1514.96 dollars, and the cost per depression-free days was US 25.66 dollars and US 28.25 dollars, for the VXR and selective serotonin reuptake inhibitors groups, respectively.. Treatment with VXR is not only expected to increase the rate of remission of symptoms but is also associated with achievement of full activity, higher number of depression-free days, productive days, and quality-adjusted days. VXR is a cost-effective treatment option for major depressive disorder.

Topics: Activities of Daily Living; Acute Disease; Ambulatory Care; Cost-Benefit Analysis; Cyclohexanols; Decision Support Techniques; Delayed-Action Preparations; Depressive Disorder, Major; Double-Blind Method; Drug Costs; Female; Fluoxetine; Fluvoxamine; Humans; Male; Paroxetine; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Venlafaxine Hydrochloride

The purpose of the present paper was to determine the suitable dose and appropriate trial duration of fluvoxamine to treat for depression. A retrospective cohort analysis was performed among depression patients who were treated in the Department of Psychiatry, Kawasaki Medical School Hospital, Kurashiki, Japan, in 2000. A total of 72 patients received fluvoxamine to treat depression. The dose-response was compared and the initial significant clinical action was examined. The percentage showing improvement after receiving a high daily dose (100-150 mg) of fluvoxamine was 73.7%, but that showing improvement on a low daily dose (50-75 mg) was 47.1%. A significant difference between the two groups was seen on Kaplan-Meier analysis and log-rank test (chi2 = 4.814; d.f. = 1; P = 0.0282). The cumulative percentage of responder patients was more than 80% at the end of a 6-week period. Fluvoxamine is recommended at a daily dose of 100 mg or 150 mg as the initial dose. If a patient does not show improvement by the end of 6 weeks the treatment regimen of fluvoxamine should be altered.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents, Second-Generation; Cohort Studies; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluvoxamine; Humans; Male; Middle Aged; Product Surveillance, Postmarketing; Retrospective Studies; Treatment Outcome

Selective serotonin reuptake inhibitors (SSRIs) and dual serotonin and noradrenaline reuptake inhibitors (SNRIs) are the most commonly prescribed class of antidepressants, yet it is not known whether one is superior to another.. The purpose of this clinical practice was to compare the periods of onset of action of fluvoxamine, paroxetine and milnacipran.. A retrospective cohort analysis was carried out among out-patients with depression treated in the Department of Psychiatry, Kawasaki Medical School Hospital, Kurashiki, Japan, in 2000 and 2001. A total of 206 patients receiving fluvoxamine, paroxetine and milnacipran were identified.. The cumulative percentage of responders receiving milnacipran reached over 80% after 4 weeks, but it did reach this level for fluvoxamine or paroxetine until after 6 weeks.. The differential period of onset of action should help guide clinicians in determining a suitable duration of antidepressants for depression.

Topics: Antidepressive Agents; Bipolar Disorder; Cyclopropanes; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Middle Aged; Milnacipran; Outpatients; Paroxetine; Psychiatric Status Rating Scales; Retrospective Studies; Time Factors; Treatment Outcome

Although it is well established that the diagnosis and treatment of depression in the elderly are major health care problems, the relative efficacy of antidepressant treatment in the elderly compared with younger adults has not been definitively established. In this study, we analyzed antidepressant response in 528 nondemented consecutive inpatients affected by a major depressive episode. The sample was divided based on a cut-off of 60 years (< or = 60 n = 354; mean age 46.6 +/- 10.4 years; > 60 n = 174; mean age 66.1 +/- 4.2 years); all the patients were treated with fluvoxamine for at least 6 weeks and they were assessed weekly by using the Hamilton Rating Scale for Depression. Fluvoxamine proved to be effective in our elderly sample, even if antidepressant response was lower in the elderly compared with that of younger subjects (chi2 = 6.27, P = 0.01). Moreover, when compared with younger subjects, the older ones showed significantly slower reduction of depressive symptoms (P = 0.0006). This difference between the 2 age groups was evident since the 2nd week of treatment, and it appeared to be independent of other clinical variables.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antidepressive Agents, Second-Generation; Bipolar Disorder; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Middle Aged; Psychological Tests; Retrospective Studies; Time Factors; Treatment Outcome

Topics: Adrenergic Uptake Inhibitors; Adult; Antidepressive Agents, Second-Generation; Bipolar Disorder; Cohort Studies; Cyclopropanes; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Middle Aged; Milnacipran; Paroxetine; Personality Inventory; Psychometrics; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Sex Factors; Treatment Outcome

Psychomotor dysfunction in depression is related to alterations in the 24-h pattern of motor activity. After antidepressant treatment the diurnal pattern may be changed due to improvement of clinical state or pharmacological actions. The purpose of this study was to evaluate in 52 depressed in-patients the effects of imipramine (tricyclic antidepressant) and fluvoxamine (SSRI) on the 24-h motor activity. Motor activity was monitored by wrist-actigraphy during a medication-free period and after 4 weeks of treatment. Clinical improvement was not different after imipramine or fluvoxamine treatment. The Hamilton depression score decreased in patients treated with imipramine, as well as in patients treated with fluvoxamine. The clinical retardation score was also reduced in both treatment groups. However, patients treated with imipramine showed higher motor activity levels during the wake period in comparison to the medication-free period, and more fragmentation of motor activity during sleep. Treatment with fluvoxamine did not result in alterations in the 24-h pattern of motor activity. The improvement of depressive mood and retardation seems to play a minor role in the change of the pattern of motor activity after imipramine.

Topics: Adult; Antidepressive Agents; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Imipramine; Male; Middle Aged; Motor Activity; Time Factors

A variable number of tandem repeats (VNTR) in the second intron of the serotonin transporter gene (STin2) has been studied in association with the susceptibility to affective disorders. Recently, it was reported that selective serotonin reuptake inhibitors were more effective in patients with major depressive disorder having the homozygous allele pair (12-copy/12-copy) of VNTR in the STin2 than in ones having other allele combinations. As the study had methodological problems, further studies are needed to confirm the above finding. Therefore, the authors investigated whether the allelic variation of VNTR in the STin2 was associated with the antidepressant response to fluvoxamine in 66 patients with major depressive disorder. Fluvoxamine was prescribed up to 200 mg/day in the dosing protocol for 6 weeks. The present study showed no significant association between the polymorphism of VNTR in the STin2 and the treatment response to fluvoxamine.

Topics: Adult; Alleles; Carrier Proteins; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluvoxamine; Gene Frequency; Genotype; Humans; Introns; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Minisatellite Repeats; Nerve Tissue Proteins; Selective Serotonin Reuptake Inhibitors; Serotonin Plasma Membrane Transport Proteins; Treatment Outcome

We examined the relationships between plasma fluvoxamine concentrations and plasma levels of cotinine and caffeine, respectively, under steady-state conditions in 30 patients who met DSM-IV criteria for a major depressive disorder and who were being treated with fluvoxamine. The daily dosages of fluvoxamine ranged from 50 to 200 mg (mean +/- SD 108 +/- 42 mg). Eleven patients were smokers and the remaining 19 were nonsmokers. The plasma fluvoxamine concentrations were significantly higher in nonsmokers (0.92 +/- 0.40 ng/ml/mg) than in smokers (0.56 +/- 0.28 ng/ml/mg); in addition, a trend towards negative correlations was observed between the plasma fluvoxamine concentrations and the plasma cotinine levels, although it was not significant. Significant positive correlations were found between the plasma fluvoxamine concentrations and the plasma caffeine levels. These findings are compatible with those in earlier reports that cytochrome P450 1A2 plays a major role in fluvoxamine metabolism.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Caffeine; Central Nervous System Stimulants; Cotinine; Cytochrome P-450 CYP1A2; Depressive Disorder, Major; Drug Interactions; Female; Fluvoxamine; Humans; Male; Middle Aged; Smoking

The presence of the long (l) variant of the serotonin (5-hydroxytryptamine: 5-HT) transporter gene-linked polymorphic region (5-HTTLPR) is reported to be associated with a more favorable and faster antidepressant effect of selective serotonin reuptake inhibitors in Caucasians. The frequency of the l allele is lower in Japanese than in Caucasians; therefore, the antidepressant effect of fluvoxamine can be not as good in Japanese as in Caucasians. The authors investigated whether 5-HTTLPR was associated with the antidepressant response to fluvoxamine in 66 Japanese patients with major depressive disorder in a protocolized-dosing 6-week study. The short (s) allele frequency was significantly higher in the responsive individuals than in the nonresponsive ones (P = .010). The present study suggests that fluvoxamine is not less effective in depressive patients carrying the s allele than in the ones carrying the l allele and it is not less effective in Japanese than in Caucasians.

Topics: Adult; Aged; Alleles; Analysis of Variance; Antidepressive Agents; Carrier Proteins; Chi-Square Distribution; Depressive Disorder, Major; Female; Fluvoxamine; Gene Frequency; Genetic Linkage; Genotype; Humans; Japan; Male; Membrane Glycoproteins; Membrane Transport Proteins; Middle Aged; Nerve Tissue Proteins; Polymorphism, Genetic; Serotonin Plasma Membrane Transport Proteins

To determine whether alpha(2)-adrenergic receptor (alpha2AR) subsensitivity is a state or a trait marker of depression, we consecutively challenged 32 drug-free depressed patients with a clonidine REM suppression test (CREST). We then treated the patients with fluvoxamine, a selective serotonin reuptake inhibitor, or mirtazapine, a selective alpha(2)-adrenergic receptor antagonist. The first 10 patients from each treatment group who recovered were given a second challenge test. The CREST values of the two treatment groups at each time point were compared, and also compared with the CREST values of a group of 10 normal subjects. Before treatment, the REM sleep response to clonidine in the two groups of patients was significantly blunted compared with the REM sleep response in the healthy subjects. After treatment, there was still an abnormal REM sleep response to clonidine in the fluvoxamine-treated patients, despite clinical recovery, but there was a normalized REM sleep response in the mirtazapine-treated patients. These results are compatible with the hypothesis that alpha2AR subsensitivity is a trait marker of depression and suggest that the effects of these two antidepressants on alpha2AR sensitivity may not be linked to the alleviation of depression.

Topics: Adrenergic alpha-Agonists; Antidepressive Agents, Tricyclic; Clonidine; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Mianserin; Mirtazapine; Receptors, Adrenergic, alpha-2; Selective Serotonin Reuptake Inhibitors; Sleep, REM

The present report describes the behavioural and psychological changes in a 55-year-old depressed male who displayed hypomania after the use of fluvoxamine in addition to other antidepressant medications. The patient experienced his first major depressive episode after the bankruptcy of his company. When fluvoxamine was prescribed at a dose of 50 mg/day in addition to sulpiride at 150 mg/day and a 50 mg dose of trazodone before sleep seven months after admission, grinning and a violation of ward rules occurred repeatedly. The patient became verbally aggressive to the staff and addicted to gambling and alcohol. Six days after the cessation of fluvoxamine, his condition remitted. None of the neuromuscular abnormalities indicative of serotonin syndrome appeared during the episode. Upon review of previous reports on manic switches induced by SSRIs and other antidepressants, we speculate that the fluvoxamine accounted for his hypomania.

Topics: Bipolar Disorder; Depressive Disorder, Major; Drug Administration Schedule; Fluvoxamine; Humans; Male; Middle Aged; Selective Serotonin Reuptake Inhibitors

Sixteen outpatients (mean age +/- SD 50.18 +/- 11.55 years; 11 females and 5 males) affected by major depression without melancholia (DSM-IV) were included in the study. The control group consisted of 11 healthy volunteers (mean age +/- SD 39.90 +/- 13.39 years; 2 females and 9 males). Patients were treated with fluvoxamine (FVX) 100-300 mg daily. Clinical assessment was performed using the Hamilton Rating Scales for Anxiety and Depression (HRS-A; HRS-D) and the Clinical Global Impression Scale (CGI) at basal time (T(0)), after 4 weeks and after 8 weeks (T(8)). Plasma and platelet amino acid levels were determined at T(0) in all the subjects and also at T(8) in depressed patients. A significant clinical improvement was observed in depressed patients according to the HRS-A (p = 0.004), HRS-D (p = 0.008) and CGI (p = 0.002). A negative correlation (r = -0.53, p = 0.049) was found between platelet levels of valine and HRS-D improvement rate. Patients showed significantly higher tyrosine/large neutral amino acids (LNAAs) and lower tryptophan/LNAAs, ratios which could represent an index of good response to a serotonergic drug like FVX.

Topics: Adult; Aged; Amino Acids; Analysis of Variance; Blood Platelets; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Middle Aged; Predictive Value of Tests; Selective Serotonin Reuptake Inhibitors

The possible association of the dopamine receptor D(2) (Ser 311Cys) and D(4) exon 3 (48 base pair repeat) gene variants with the antidepressant activity of selective serotonin reuptake inhibitors (SSRIs) was investigated in a sample of 364 inpatients affected by a major depressive episode treated with fluvoxamine, 300 mg/day (n=266), or paroxetine, 20-40 mg/day (n=98). The severity of depressive symptoms was assessed weekly with the Hamilton Rating Scale for Depression. Dopamine receptor D(2) (DRD2) and dopamine receptor D(4) (DRD4) allelic variants were determined in each subject by polymerase chain reaction. We observed that DRD2 and DRD4 variants were not associated with response to SSRI treatment. Possible stratification factors, such as sex, diagnosis, presence of psychotic features, depressive symptoms at baseline, paroxetine and fluvoxamine plasma levels, and pindolol augmentation did not significantly influence the observed results. The investigated DRD2 and DRD4 gene variants therefore do not seem to play a major role in the antidepressant activity of SSRIs, at least in the present sample.

Topics: Depressive Disorder, Major; Exons; Female; Fluvoxamine; Gene Expression; Gene Frequency; Humans; Male; Middle Aged; Paroxetine; Receptors, Dopamine D2; Receptors, Dopamine D4; Selective Serotonin Reuptake Inhibitors

We investigated the association between fluvoxamine and nausea from various viewpoints. The incidence of nausea induced by fluvoxamine was 29% (12/41). Plasma 5-hydroxyindoleacetic acid (p5-HIAA) levels after fluvoxamine administration were significantly higher in patients with nausea (6.6+/-3.4 ng/ml) than in those without nausea (3.5+/-2.7 ng/ml). On the other hand, no significant differences were found between patients with and patients without nausea in terms of sex, age, initial and maximum dosages of fluvoxamine and its plasma concentrations, and clinical response to fluvoxamine. However, the incidence of nausea in patients who were initially administered fluvoxamine at under 50 mg/day was significantly lower than in those who were started at above 50 mg/day. In addition, mosapride, a member of the benzamide family, was effective in alleviating fluvoxamine-induced nausea. These results suggest that fluvoxamine-induced nausea is associated with hyperactivity in serotonergic neurons.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Benzamides; Depressive Disorder, Major; Dose-Response Relationship, Drug; Female; Fluvoxamine; Humans; Hydroxyindoleacetic Acid; Male; Middle Aged; Morpholines; Nausea; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index

Topics: Attention Deficit and Disruptive Behavior Disorders; Child; Depressive Disorder, Major; Fluvoxamine; Humans; Male; Paroxetine; Suicide, Attempted

We assessed the pattern of changes in depressive symptoms in delusional depressed inpatients treated openly with 300 mg/day of fluvoxamine for 6 weeks. We studied 59 inpatients affected by bipolar (n=23) and major depressive (n=36) disorders with psychotic features (DSM-IV) who showed complete responses to fluvoxamine treatment. Responses were evaluated using the Hamilton Rating Scale for Depression (HAMD-21, divided into: Core, Activity, Psychic anxiety, Somatic anxiety and Delusion clusters) administered at baseline and weekly until the 6th week. Random Regression Model (RRM) analysis was used to investigate the longitudinal time course of HAMD clusters. HAMD depressive symptom clusters decreased in a parallel manner from baseline to the end of the 6-week trial. The RRM analysis revealed no significant difference between HAMD clusters and the time course of the total HAMD score during treatment. Our data indicate that there is a simultaneous decrease in depressive symptoms during antidepressant treatment of delusional depressives.

Topics: Adult; Antidepressive Agents, Second-Generation; Bipolar Disorder; Delusions; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Longitudinal Studies; Male; Middle Aged; Personality Inventory; Psychiatric Status Rating Scales; Treatment Outcome

A reversed-phase high-performance liquid chromatography (HPLC) method with fluorimetric detection, which allows the simultaneous determination of plasma concentrations of four selective serotonin reuptake inhibitors (SSRIs) is presented. Fluvoxamine, paroxetine, sertraline, and fluoxetine were extracted from plasma with ethyl acetate and then derivatized with dansyl chloride. The analytes were separated using Hypersyl ODS C18 (5 microm) 250 x 4.6 mm column (ThermoQuest, Runcorn, UK). For continuous gradient separation, the mobile phase consists of two eluents, acetonitrile and potassium phosphate buffer (10 mmol/L, pH 7.2) at total flow rate of 1.5 mL/min. Detection was carried out at lambda exc = 366 nm and lambda em = 490 nm. The authors found recoveries of 90% to 95% for fluvoxamine, 94% to 100% for paroxetine, 88% to 95% for sertraline, 93% to 100% for fluoxetine, and 97% to 100% for internal standard (nortriptyline). Imprecision of the method ranged from 2.5% to 8.9%. The assay was linear from 10 to 1500 ng/mL for sertraline, and from 5 to 1500 ng/mL for the other drugs. The authors conclude that this method is suitable for monitoring antidepressant therapy. In addition, the authors report the effects of adding paroxetine to fluvoxamine on plasma levels in a group of patients in combined drug therapy.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Chromatography, High Pressure Liquid; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Interactions; Drug Therapy, Combination; Female; Fluorometry; Fluoxetine; Fluvoxamine; Humans; Linear Models; Male; Middle Aged; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sensitivity and Specificity; Sertraline

The effects of antidepressants on sleep in depression have been extensively investigated, although to date there have been relatively few studies of newer drug classes such as specific serotonin reuptake inhibitors (SSRIs). All reported studies on SSRIs have been conducted in patients admitted to sleep laboratories and very few longitudinal studies have continued to measure sleep beyond 5 weeks of treatment. The growing trend towards outpatient and community care has highlighted the need for studies of sleep in depression in a more naturalistic setting, and during longer periods of treatment in line with recommended clinical practice.. To establish if the changes in sleep architecture and continuity described during early treatment with SSRIs persist after 3 months, to relate these changes to clinical state, and to establish whether home recordings would yield similar results to previous laboratory studies.. We have recorded objective sleep parameters in 12 depressed patients before and during 12-week treatment with an SSRI, fluvoxamine. All the sleep recordings were performed in the patients' own homes, using the Oxford Medilog system.. At 12 weeks, 7/12 patients had responded (HAM-D decreased by > 50%). REM latency showed the expected increase early in treatment; this change was less obvious at weeks 3 and 12. Amount of REM sleep was decreased at day 2 and week 3, but returned to baseline by week 12. Slow wave sleep was slightly increased at day 2 and decreased at week 12. Of the sleep continuity measures, the only significant change was in sleep onset latency, which was increased at week 3; the other measures showed non-significant worsening at night 2 and week 3, but most were better than baseline by 12 weeks. Subjective sleep (the three sleep items on the HAM-D) showed a progressive improvement over time, especially in the responders.. The effects of the SSRI fluvoxamine on objective sleep measures are in the direction predicted by its pharmacological actions and some persist for at least 12 weeks. In addition subjective appraisal of sleep is strongly affected by mood state. All patients found the home recording procedure acceptable and only minimally disruptive.

Topics: Adult; Affect; Analysis of Variance; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Middle Aged; Polysomnography; Selective Serotonin Reuptake Inhibitors; Sleep, REM

The cytochrome enzyme P450 2D6 (CYP2D6) is thought to play a role in the human metabolism of fluvoxamine. Levomepromazine is a potent inhibitor of CYP2D6. We coadministered a low dosage of levomepromazine and fluvoxamine in 15 patients and found that the low dosage of levomepromazine was effective in counteracting the fluvoxamine-induced insomnia and did not increase plasma fluvoxamine levels. These results suggest that the inhibition of CYP2D6 by levomepromazine has little effect on fluvoxamine metabolism. Therefore, a low dosage of levomepromazine, used as a hypnotic agent, appears to be effective and safe when coadministered with fluvoxamine. Since this was a pilot study without a placebo control, a double-blind placebo-controlled study is needed to confirm our preliminary findings.

Topics: Adult; Aged; Aged, 80 and over; Cytochrome P-450 CYP2D6 Inhibitors; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Male; Methotrimeprazine; Middle Aged; Panic Disorder; Sleep Initiation and Maintenance Disorders; Treatment Outcome

Topics: Adult; Creatine Kinase; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Administration Schedule; Fluvoxamine; Humans; Male; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome; Stress Disorders, Post-Traumatic

This investigation of fluvoxamine and fluoxetine-norfluoxetine distributions in vivo at steady-state and of quantitative kinetics in brain and plasma after drug therapy interruption was performed by fluorine nuclear magnetic resonance spectroscopy (19F MRS), spectroscopic imaging (MRSI), and plasma HPLC on 12 subjects treated for depression. MRSI suggests a homogeneous distribution of 19F MRS visible fluvoxamine mainly in brain. Fluvoxamine steady-state brain concentrations (12 +/- 5 microM; n = 13) and brain-to-plasma concentration ratios (10 +/- 2; n = 12) were similar to those of combined fluoxetine-norfluoxetine (CF-norfluoxetine) (13 +/- 6 microM; n = 4 and 10 +/- 6; n = 4). Fluvoxamine brain elimination half-life (79 +/- 24 hours; n = 4) was significantly shorter than that of CF-norfluoxetine (382 +/- 48 hours; n = 2). Fluvoxamine brain-to-plasma-half-life-ratio was 2.2 +/- 0.3 (n = 4), contrarily to CF-norfluoxetine (1.0 +/- 0.3; n = 2). This study shows that quantitative pharmacokinetics in target organs by 19F MRS in vivo should prove useful for understanding and investigating outcome of treatment modifications and side effects.

Topics: Adult; Aged; Brain; Depressive Disorder, Major; Female; Fluorine Radioisotopes; Fluoxetine; Fluvoxamine; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Selective Serotonin Reuptake Inhibitors

Topics: Aged; Antidepressive Agents, Second-Generation; Depressive Disorder, Major; Fluvoxamine; Humans; Libido; Male; Sexual Behavior

We recently reported that fluoxetine or paroxetine, two selective serotonin reuptake inhibitors (SSRIs), when administered to rats, increase the brain content of the neurosteroid 3alpha-hydroxy-5alpha-pregnane-20-one (3alpha5alpha-ALLO) without altering the brain content of other neurosteroids. ALLO (3alpha5alpha and 3alpha5beta isomers) binds with high affinity to various gamma-aminobutyric acid (GABA) receptor A subtypes and facilitates the action of GABA at these receptors. We hypothesized that the increase of ALLO brain content induced by treatment with SSRIs could contribute to alleviating the anxiety and dysphoria associated with the symptomatology of major unipolar depression. We measured ALLO content in four cisternal-lumbar fractions of cerebrospinal fluid (CSF) before and 8-10 weeks after treatment with fluoxetine or fluvoxamine in 15 patients with unipolar major depression. The concentration of ALLO ( approximately 40 fmol/ml in each CSF fraction of three control subjects) was about 60% lower in patients with major unipolar depression. However, in the same patients, fluoxetine or fluvoxamine treatment normalized the CSF ALLO content. Moreover, a statistically significant correlation (r = 0.58; P < 0.023; n = 15) existed between symptomatology improvement (Hamilton Rating Scale for Depression scores) and the increase in CSF ALLO after fluoxetine or fluvoxamine treatment. The CSF content of PREG and PROG remained unaltered after treatment and failed to correlate with the SSRI-induced increase of CSF ALLO. The normalization of CSF ALLO content in depressed patients appears to be sufficient to mediate the anxiolytic and antidysphoric actions of fluoxetine or fluvoxamine via its positive allosteric modulation of GABA type A receptors.

Topics: Adult; Depressive Disorder, Major; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Pregnanolone; Psychometrics; Selective Serotonin Reuptake Inhibitors; Stereoisomerism

Plasma and platelet levels of 18 amino acids were measured in 29 outpatients (mean age +/- SD 47.41 +/- 10.85 years; 14 F, 15 M) affected by major depression (DSM IV) and in 28 healthy volunteers (mean age 42.46 +/- 14.19 years; 12 F, 16 M). Plasma and platelet levels of amino acids tended to be higher in depressed patients than in healthy controls. In particular, glutamate, taurine and lysine plasma levels and aspartate, serine and lysine platelet levels were significantly higher. Tryptophan/large neutral amino acids ratio (trp/LNAAs) was significantly lower in depressed patients. Fluvoxamine treatment did not influence plasma and platelet levels of amino acids or trp/LNAAs ratio.

Topics: Adult; Aged; Amino Acids; Antidepressive Agents, Second-Generation; Blood Platelets; Depressive Disorder, Major; Female; Fluvoxamine; Humans; Male; Middle Aged; Reference Values; Tryptophan

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

Depressive illness has been reported to interfere with effortful processing, which requires conscious attention. The aim of this study was to evaluate divided attention in depressed patients, as a function of the degree of difficulty of the task performed. Tasks designed to measure unimodal and bimodal reaction times were presented to 10 patients with major depression and 10 normal control subjects. Performance was evaluated both before treatment when the patients were depressed and after treatment when they had recovered. Unlike the unimodal trials, the bimodal reaction time tasks were designed to evaluate decision-making under conditions in which attention was divided between two perceptual channels. Reaction times were measured under two different conditions in order to assess the extent of the response delay induced by divided attention, modality shifting, and decision processing. During simple response tasks, the depressed patients displayed significantly greater lengthening of reaction times when their attention was divided between two perceptual channels. This cross-modal delay effect occurred both for stimuli of the same modality and when shifting between modalities. The cross-modal delay effect was evident only for the choice tests in both the depressed and the recovered patients, but only the recovered patients were as accurate as the control subjects. These results suggest that the need for decision processing in depressed patients results in a failure to allocate the mental resources required to complete interchannel shifting, when attention is divided between two perceptual channels. These data are consistent with the hypothesis that attentional regulation is impaired in major depression.

Topics: Adult; Antidepressive Agents, Second-Generation; Attention; Decision Making; Depressive Disorder, Major; Female; Fluoxetine; Fluvoxamine; Humans; Male; Mianserin; Middle Aged; Reaction Time