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To evaluate whether serotonin reuptake inhibition is critical to the treatment of obsessive-compulsive disorder, 40 outpatients with a principal diagnosis of obsessive-compulsive disorder were randomized in a double-blind fashion to 8 weeks of treatment with either the serotonin reuptake inhibitor fluvoxamine maleate (n = 21) or the norepinephrine reuptake inhibitor desipramine hydrochloride (n = 19). Fluvoxamine was significantly better than desipramine in reducing the severity of obsessive-compulsive symptoms, as measured by the Yale-Brown Obsessive Compulsive Scale and by the global response rate ("responder" equaling "much improved"). Eleven of 21 patients were responders with fluvoxamine compared with 2 of 19 patients with desipramine. Fluvoxamine, but not desipramine, was also effective in reducing the severity of "secondary" depression. Fluvoxamine-induced improvement in symptoms of obsessive-compulsive disorder was not correlated with the severity of baseline depressive symptoms. This study provides additional evidence that the acute serotonin reuptake properties of a drug are predictive of its anti-obsessive-compulsive efficacy. It is hypothesized that the mechanism of action of serotonin reuptake inhibitors in obsessive-compulsive disorder may be related to chronic treatment-induced adaptive changes in presynaptic serotonin receptor function (eg, autoreceptor desensitization) and/or indirect influences on dopaminergic function (eg, in the basal ganglia).
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PMID:Specificity of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder. Comparison of fluvoxamine and desipramine. 202 4

One hundred and sixty patients with a primary diagnosis of obsessive-compulsive disorder were enrolled in a multicentre, randomized, double-blind, placebo-controlled study of fluvoxamine. After a placebo washout phase, patients were randomized to treatment with placebo or fluvoxamine (100-300 mg/day) for 10 weeks. Seventy-eight patients in each group were evaluable for efficacy. Fluvoxamine was significantly more effective than placebo as assessed by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the National Institute of Mental Health Obsessive-Compulsive (NIMH-OC) scale and the Global Improvement item of the Clinical Global Impression (CGI) scale. The percentage of patients classified as "responders" (much or very much improved according to the Global Improvement item) was also significantly higher in the fluvoxamine group from Week 6 onwards, with 33.3% of fluvoxamine-treated patients and 9.0% of those given placebo classified as "responders" at endpoint. The "responders" to fluvoxamine experienced a substantial clinical benefit as reflected in decreases in their Y-BOCS and NIMH-OC scores. Fluvoxamine was well tolerated with the majority of adverse events considered mild or moderate.
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PMID:Treatment of obsessive-compulsive disorder with fluvoxamine: a multicentre, double-blind, placebo-controlled trial. 873 10

Obsessive-Compulsive (OC) symptoms are observed in a substantial proportion of schizophrenic patients and pose a significant therapeutic challenge. Based on findings of the benefit of the anti-obsessive agent clomipramine, we designed an open-label study to examine the effect of adding the serotonin-selective reuptake inhibitor (SSRI) fluvoxamine to the ongoing antipsychotic regimen of schizo-obsessive patients. The study population consisted of ten neuroleptic-stabilized chronic schizophrenic patients with OC symptoms. Fluvoxamine (up to 150 mg/day) was added to the ongoing antipsychotic treatment, which remained unchanged for the entire 12-week trial period. The patients were evaluated before the trial and at weeks 1, 2, 4, 6, 8 and 12 (end point) with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Schedule for Assessment of Positive Symptoms and the Schedule for Assessment of Negative Symptoms. The results showed a significant improvement in obsessions (P < 0.02) (but not compulsions) and both positive (P < 0.01) and negative (P < 0.05) schizophrenic symptoms. By the end of the trial, three patients showed a more than 50% reduction in the Y-BOCS score, with complete amelioration of the OC symptoms in one of them. Three patients were dropped from the study during the first 4 weeks, two because of aggressiveness and one because of psychotic exacerbation. No exacerbation or new onset of extrapyramidal side-effects (EPS), as measured by the Barnes Akathisia Scale (BARS) and the Simpson-Angus Scale (SAS), was noted during the course of the trial and there were no other significant clinical side-effects of fluvoxamine addition. We conclude that fluvoxamine may be an effective adjunctive agent in some schizo-obsessive patients.
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PMID:Fluvoxamine treatment of obsessive-compulsive symptoms in schizophrenic patients: an add-on open study. 1022 Jan 24

Some meta-analyses have suggested that the selective serotonin reuptake inhibitors (SSRIs) are less effective than clomipramine in the treatment of obsessive-compulsive disorder (OCD). The aim of this double-blind, randomised, multicentre study was to directly compare the efficacy and safety of fluvoxamine and clomipramine in patients with OCD. A total of 227 patients were randomised to flexible doses of fluvoxamine or clomipramine (both 150-300 mg/day) for 10 weeks. Fluvoxamine and clomipramine were both clinically effective and there were no statistically significant differences between the two treatment groups, at any visit, on the National Institute of Mental Health Obsessive-Compulsive global rating scale, the Yale-Brown Obsessive-Compulsive scale (total score and obsession and compulsion subscores), the Clinical Global Impression severity of illness and global improvement subscales, the Clinical Anxiety Scale and the 17-item Hamilton Depression Rating Scale. However, there were differences in safety between the two treatments. Compared with fluvoxamine-treated patients, those treated with clomipramine had more anticholinergic side effects (dry mouth, constipation and tremor) and premature withdrawals due to adverse events (18 versus 9). The results from this controlled study indicate that fluvoxamine is as effective as clomipramine in the treatment of OCD but has a better tolerability profile. Copyright 2001 John Wiley & Sons, Ltd.
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PMID:Fluvoxamine in obsessive-compulsive disorder: similar efficacy but superior tolerability in comparison with clomipramine. 1240 54

BACKGROUND: There is emerging evidence that postpartum women are at risk for the development or worsening of obsessive-compulsive disorder. The purpose of this study was to provide data regarding the demographics, phenomenology, associated psychiatric comorbidity, family history, and response to open treatment with fluvoxamine in subjects with postpartum-onset obsessive-compulsive disorder. METHOD: Seven consecutive subjects were recruited from an outpatient obstetrical practice and by advertisement. Subjects completed the Structured Clinical Interview for DSM-IV, the Yale-Brown Obsessive Compulsive Scale, and a semistructured interview for family history, demographic data, and clinical features. Three of the 7 subjects participated in a 12-week, open-label trial of fluvoxamine treatment of postpartum-onset DSM-IV obsessive-compulsive disorder. RESULTS: The women described a mean age at onset of 28 years, and 4 subjects had a chronic course. Six subjects reported onset after the birth of their first child, and the mean time to onset was 3.7 weeks postpartum. All subjects experienced both obsessions and compulsions and reported aggressive obsessions that involved their children. None of the subjects acted on their obsessions to harm the children, but 5 reported dysfunctional mother-child behavior. All 7 subjects met criteria for at least 1 comorbid psychiatric disorder, with a mood disorder the most common. Family histories were notable for high rates of mood disorders and psychoactive substance use disorders in first-degree relatives. Two of the 3 subjects who entered the open-label trial of fluvoxamine experienced a positive response, defined as a 30% or greater decrease in the total score of the Yale-Brown Obsessive Compulsive Scale. CONCLUSION: Obsessive-compulsive disorder may present in the postpartum period and become chronic. Symptoms of the disorder may adversely affect the mother-child relationship, and it is important to assess for obsessions and compulsions in postpartum women who present with anxiety and/or depression. Fluvoxamine may be effective in reducing the symptoms of postpartum-onset obsessive-compulsive disorder. Controlled studies are needed to confirm these findings.
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PMID:A Case Series of Women With Postpartum-Onset Obsessive-Compulsive Disorder. 1501 82

The effectiveness of Fluvoxamine was compared to that of Cognitive Therapy (CT) in a 12-week randomized controlled trial (RCT) in 48 patients with obsessive-compulsive disorder (OCD), who were treatment-resistant to a previous behavior therapy (BT). A considerable amount of patients did not comply with the assigned treatment and switched treatments. The aim of this study was to identify patient characteristics predictive of assignment compliance and to study whether these characteristics were related to outcome. A logistic model, based on psychological and social patient characteristics, in addition to or in interaction with the assignment, was used for the explanation of compliance with treatment assignment. Especially patients who have a higher score on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) tend to comply with the effective Fluvoxamine treatment. The same set of variables was related to both compliance and outcome of therapy received. Therefore, the logistic model of compliance could be used to reduce the positive bias of As-Treated analysis (AT). The difference between the results of Fluvoxamine and Cognitive Therapy remained statistically significant after correcting for the positive bias as the result of assignment refusal and after applying the assumption that two drop-out patients needed imputation of lesser results.
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PMID:Assignment refusal and its relation to outcome in a randomized controlled trial comparing Cognitive Therapy and Fluvoxamine in treatment-resistant patients with obsessive compulsive disorder. 2561 76