Fluvoxamine maleate, a serotonergic antidepressant; A comparison with chlorimipramine

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

氟伏沙明联合阿立哌唑治疗难治性强迫症对照研究

目的 探讨氟伏沙明联合阿立哌唑治疗难治性强迫症的临床疗效和安全性.方法 将56例强迫症患者随机分为两组,每组28例,两组均口服氟伏沙明治疗,研究组联合阿立哌唑治疗.观察8周.于治疗前及治疗2周、4周、6周、8周末采用Yale-Brown强迫量表评定临床疗效,副反应量表评定不良反应.结果 治疗4周末起两组Yale-Brown强迫量表评分均较治疗前有显著下降(P＜0.01),但研究组治疗4周、6周、8周末均较对照组下降更显著(P＜0.05或0.01).治疗8周末,研究组总有效率为85.7%、对照组为67.8%,研究组疗效优于对照组.治疗4周末研究组副反应量表评分显著高于对照组(P＜0.01),其他各时段评分两组差异均无显著性(P＞0.05);两组不良反应均轻微,研究组以神经系统不良反应为主,对照组以植物神经系统反应为主.结论 氟伏沙明联合阿立哌唑能增强抗强迫效应,治疗难治性强迫症起效快,疗效显著,安全性高,依从性好,显著优于单用氟伏沙明治疗.     

Clinical features and treatment outcome in Japanese patients with social anxiety disorder: chart review study

The lifetime prevalence of social anxiety disorder (SAD) is high at 3-13%, but there have been only limited reports investigating the clinical features of this disorder in a large number of Japanese patients. The authors have conducted a retrospective, chart review study of 52 patients with SAD and obtained the following results. (i) The proportion of SAD in first visit outpatients at the Department of Psychiatry, Niigata University Medical and Dental Hospital, Niigata, Japan, was 1.04%. The male : female ratio was 1:0.73, so male patients appeared to be more common in the sample. (ii) With regard to subtype, generalized type (73% of the patients) was more common than non-generalized type (27%). (iii) The mean age of onset was 18.6 +/- 7.8 years, and there was a trend towards onset of disease at a younger age in the generalized type compared to the non-generalized type. (iv) The most common chief complaint was anxiety and tension in front of others (40.4%). (v) Pharmacotherapy resulted in improvement in 63.5% of the patients. Treatment by fluvoxamine and alprazolam resulted in high response rates of more than 70%.     

Cognition and depression: the effects of fluvoxamine,a sigma‐1 receptor agonist,reconsidered

Cognitive impairment is a primary feature of patients with major depressive disorder (MDD) and is characterised by stress‐induced neural atrophy. Via alpha‐adrenergic, anti‐cholinergic and anti‐histaminic activities, several antidepressants can cause significant counter‐therapeutic cognitive impairment. Evidence is emerging of the involvement of sigma‐1 receptor agonism in the mechanism of action of some antidepressants, notably fluvoxamine. Sigma‐1 receptors are abundant in areas affected by depression/stress‐induced cerebral atrophy and their ligands have a unique pharmacological profile; they may promote neurogenesis and initiate adaptive neural plasticity as a protection/reaction to stress. Fluvoxamine, as a potent sigma‐1 receptor agonist, has shown ameliorating effects in animal models of psychosis, depression, stress, anxiety, obsessive‐compulsive disorder (OCD) and aggression and has been shown to improve cognitive impairments. In humans, fluvoxamine may repair central nervous system (CNS) atrophy and restore cognitive function. The current review explores the mechanisms through which sigma‐1 receptors can modulate cognitive function and examines how antidepressant therapy with fluvoxamine may help improve cognitive outcomes in patients with depression. Copyright © 2010 John Wiley & Sons, Ltd.     

Treatment of bulimia nervosa with fluvoxamine: A randomized controlled trial

Bulimia nervosa (BN) is one of the most common eating disorders in industrialized societies. It has been suggested that reduced serotonin activity triggers some of the cognitive and mood disturbances associated with BN. For this reason, the pharmacologic treatment of BN consists mainly of selective serotonin reuptake inhibitors (SSRIs), which have been proven effective. At present, the physiologic bases of this disorder are not yet completely understood. We conducted a randomized controlled trial to verify the efficacy of the SSRI fluvoxamine in patients with a diagnosis of BN. Twelve female outpatients aged 21 to 34 years with a diagnosis of BN-binge purging (as defined by the fourth edition of theDiagnostic and Statistical Manual of Mental Disorders [DSM IV]) were randomly assigned to 2 treatment groups: the fluvoxamine 200 mg/day group and the placebo group. The patients underwent weekly clinical assessments for 12 weeks. At the end of the observation period, there was a statistically significant reduction in the number of binge-eating crises and purging episodes in the fluvoxamine group compared with placebo. In no case was treatment interrupted because of emergent side effects. These findings support the hypothesis that fluvoxamine is well tolerated and effective in reducing binge-eating crises and purging episodes in patients with BN.     

Fluvoxamine augmentation in risperidone-resistant schizophrenia: an open trial

We investigated the efficacy and safety of augmenting risperidone with fluvoxamine for the treatment of residual positive and negative symptoms in patients with chronic schizophrenia who had shown an incomplete response to risperidone. A total of 30 patients completed the open trial over a 12-week period during which fluvoxamine was added to risperidone. The result from the positive and negative syndrome scale (PANSS) and Simpson-Angus extrapyramidal effects (S-A) scale were examined at baseline, 1, 2, 4, 8 and 12 weeks of treatment. There were no significant differences in PANSS positive, negative and general psychopathology scores, or in S-A scale scores at any point during the treatment. These results suggest that fluvoxamine appears to be ineffective in augmenting the risperidone treatment response in chronic schizophrenic patients. Further controlled trials will be needed to confirm this observation.     

Effects of aging on serotonin transporter availability and its response to fluvoxamine in the living brain: PET study with [(11)C](+)McN5652 and [(11)C](-)McN5652 in conscious monkeys

Age-related changes in the serotonin transporter (SERT) in the living brains of conscious young (5.9 +/- 1.8 years old) and aged (19.0 +/- 3.3 years old) monkeys (Macaca mulatta) were evaluated in combination with [(11)C](+)McN5652 and its inactive enantiomer [(11)C](-)McN5652 by high-resolution positron emission tomography (PET). For the quantitative analysis of SERT binding in vivo, two serial PET scans with [(11)C](+)McN5652 and [(11)C](-)McN5652 were performed in the same animals in a day and the differences in radioactivities of [(11)C](+)McN5652 vs. [(11)C](-)McN5652 measured from 41-91 min postinjection were calculated as an estimate of specific ligand binding. Higher specific binding of SERT was observed in the thalamus and striatum, regions known to contain high densities of SERT by in vitro assay, with intermediate levels in the pons, hippocampus, cingulate gyrus, and cortical regions and lower levels in the cerebellum in both young and aged monkeys. Almost all regions assayed except the cerebellum showed significant age-related decreases in the specific binding of SERT, which showed reverse correlation with cortisol level in plasma. When the SERT blocker fluvoxamine (1 mg/kg) was administered intravenously 30 min after tracer injection, specific binding of SERT was displaced in both age groups. However, the degree of displacement was more marked in young than in aged monkeys. Cortisol level in plasma was significantly higher in aged than in young animals. These observations demonstrate the usefulness of the combined use of [(11)C](+)McN5652 and [(11)C](-)McN5652 as an indicator for the age-related changes in cortical SERT measured noninvasively by PET. In addition, these observations suggest that the age-related impairment of SERT sensitivity for fluvoxamine might be related to the reduced efficacy of antidepressant therapy in elderly patients with depression.     

Restlessness related to SSRI withdrawal

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

A double-blind,placebo-controlled trial of fluvoxamine in binge eating disorder: a high placebo response

Summary Twenty subjects with binge eating disorder were randomly assigned to flexible-dose fluvoxamine or placebo for 12 weeks. A significant reduction in binge frequency, Beck Depression Inventory scores and the eating concern, shape concern and weight concern subscales of the Eating Disorder Examination were noted for both fluvoxamine (n = 9) and placebo (n = 11) groups. There were no significant differences between fluvoxamine and placebo for any treatment outcome variables. The findings from this small trial contribute to the inconsistent results of antidepressant studies in binge eating disorder. Received August 7, 2002; accepted January 26, 2003 Published online April 23, 2003 RID="*" ID="*"  This study was presented as a poster at the 9^th International Conference on Eating Disorders, May, 2000, New York, NY. Supported in part by a grant from Solvay Pharmaceuticals. Correspondence: Teri Pearlstein, M.D., Assistant Professor, Department of Psychiatry and Human Behavior, Brown Medical School, Director, Women's Behavioral Health Program, Women and Infants Hospital, 101 Dudley Street, Providence, RI 02905, U.S.A.; e-mail: Teri_Pearlstein@brown.edu