Fluvoxamine treatment of obsessive-compulsive symptoms in schizophrenic patients: an add-on open study

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.     

Fluvoxamine dose-dependent interaction with haloperidol and the effects on negative symptoms in schizophrenia

Augmentation with low-dose fluvoxamine (50–100 mg/day) to antipsychotic treatment may improve the negative symptoms in schizophrenic patients, but involves a risk of drug-drug interaction. We studied the effects of fluvoxamine on plasma concentrations of haloperidol and reduced haloperidol, and their clinical symptoms, in haloperidol treated patients. Twelve schizophrenic inpatients with prevailingly negative symptoms receiving haloperidol 6 mg/day were additionally treated with incremental doses of fluvoxamine for 6 weeks (25, 75 and 150 mg/day for 2 weeks each). Plasma drug concentrations were monitored together with clinical assessments before and after each phase of the three fluvoxamine doses. Geometric mean of haloperidol concentrations during coadministration of fluvoxamine 25, 75 and 150 mg/day were 120% (95%CI; 114–127%), 139% (95%CI; 130–149%), and 160% (95%CI; 142–178%) of those before fluvoxamine coadministration, respectively. We found positive correlations between increase in plasma haloperidol concentrations and plasma fluvoxamine concentrations. Scores in negative symptoms were significantly reduced after fluvoxamine coadministration, whereas no changes were observed in the other psychiatric symptoms or any subgrouped side effects. Therefore, this study indicates that fluvoxamine increases plasma haloperidol concentrations in a dose-dependent manner. However, relatively small elevations in haloperidol concentration did not lead to the development of extrapyramidal symptoms under the conditions of this study.     

A placebo-controlled inpatient comparison of fluvoxamine maleate and imipramine in major depression

Fluvoxamine, a selective serotonin reuptake inhibitor, was investigated in a 6-week double-blind study among severely ill inpatients with DSM-III major depression. All but 1 patient also fulfilled criteria for melancholia. Following a 3-day placebo wash-out patients were randomly assigned to fluvoxamine, imipramine or placebo. Sixty of 81 patients completed at least 2 weeks following wash-out and were evaluated for efficacy. Analysis of covariance (controlling for baseline scores) showed significant (p less than 0.05) differences on CGI severity and BPRS total and a similar trend (p = 0.08) on the Hamilton Depression Scale. Fluvoxamine was superior (p less than or equal to 0.02) to both placebo and imipramine on these measures. Fluvoxamine's most common adverse effects were nausea and agitation. The number of fluvoxamine patients withdrawn for side-effects was less than imipramine and not significantly different than placebo. Fluvoxamine was not associated with significant changes in vital signs, ECG or laboratory tests. The results therefore indicate that fluvoxamine is a safe and highly effective treatment for hospitalized patients with major depression.     

Fluvoxamine. An updated review of its use in the management of adults with anxiety disorders

Fluvoxamine is a potent and selective serotonin reuptake inhibitor (SSRI) that has little or no effect on other monoamine reuptake mechanisms. Relative to other SSRIs, fluvoxamine is a weak inhibitor of cytochrome P450 (CYP) 2D6, a moderate inhibitor of CYP2C19 and CYP3A4 and a potent inhibitor of CYP1A2. In randomised, double-blind trials. fluvoxamine 100 to 300 mg/day for 6 to 10 weeks significantly reduced symptoms of obsessive-compulsive disorder (OCD) compared with placebo. Response rates of 38 to 52% have been reported with fluvoxamine, compared with response rates of 0 to 18% with placebo. In patients with OCD, fluvoxamine had similar efficacy to that of clomipramine and, in smaller trials, the SSRIs paroxetine and citalopram and was significantly more effective than desipramine. Maintenance therapy with fluvoxamine may reduce the likelihood of relapses in up to 67% of patients with OCD. Fluvoxamine < or = 300 mg/day for 6 to 8 weeks was as effective as imipramine in patients with panic disorder, and significantly more effective than placebo. In addition, treatment with fluvoxamine < or = 300 mg/day for > or = 8 weeks improved symptoms of social phobia (social anxiety disorder), post-traumatic stress disorder (PTSD), pathological gambling, compulsive buying, trichotillomania, kleptomania, body dysmorphic disorder, eating disorders and autistic disorder. Large trials comparing the efficacy of fluvoxamine and other SSRIs in patients with anxiety disorders are warranted. Fluvoxamine is generally well tolerated; in postmarketing studies, nausea was the only adverse event occurring in >10% of patients with less commonly reported events including somnolence, asthenia, headache, dry mouth and insomnia. Fluvoxamine is associated with a low risk of suicidal behaviour, sexual dysfunction and withdrawal syndrome. Fewer anticholinergic or cardiovascular events are associated with fluvoxamine than tricyclic antidepressants. Although comparative data are lacking, the tolerability profile of fluvoxamine appears to be broadly similar to those of other SSRIs. CONCLUSION: Fluvoxamine has demonstrated short term efficacy in the treatment of OCD, panic disorder, social phobia, PTSD and in a range of obsessive-compulsive spectrum disorders. The drug is as effective as clomipramine in patients with OCD but appears to have a better tolerability profile. On the basis of current treatment guidelines, fluvoxamine, like other SSRIs, is recommended as first-line treatment for a number of anxiety disorders. It appears to offer some pharmacokinetic advantages and a different drug interaction profile to the other SSRIs with a broadly similar spectrum of adverse events. However, direct comparisons are required to assess the relative efficacy and tolerability of the different agents of this drug class.     

Spotlight on fluvoxamine in anxiety disorders in children and adolescents

Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) which may be used for the management of anxiety disorders in children and adolescents. Absorption of fluvoxamine was similar in adolescents to that in adults, which suggests that the maximum dosage of the drug for patients aged between 12 and 17 years can be as high as 300 mg/day. However, steady-state plasma fluvoxamine concentrations were 2 to 3 times higher in children (aged between 6 and 11 years) than in adolescents; thus, the maximum fluvoxamine dosage recommended for children is 200 mg/day. Fluvoxamine (50 to 300 mg/day) for 8 to 16 weeks significantly reduced symptoms of obsessive-compulsive disorder (OCD) [measured across multiple assessment scales] compared with placebo in a well controlled trial in paediatric patients (n = 120) or from baseline in noncomparative trials in adolescent (n = 20) or paediatric (n = 16) patients. Improvements with fluvoxamine (up to 200 mg/day) were observed for up to 1 year in 98 patients with OCD in a noncomparative trial. The drug (up to 250 or 300 mg/day) also improved symptoms of anxiety compared with placebo in an 8-week well controlled trial in 128 paediatric patients with social phobia, separation anxiety disorder or generalised anxiety disorder (GAD). Fluvoxamine (50 to 300 mg/day) appears to be well tolerated in paediatric patients, with most adverse events with the drug (except abdominal discomfort, which occurred more often in patients receiving fluvoxamine) occurring with a similar incidence to those with placebo. The most common adverse events involved the CNS or gastrointestinal system. Most adverse events reported by paediatric patients with OCD were similar to those reported by adults. In conclusion, fluvoxamine is generally well tolerated and has demonstrated short-term efficacy compared with placebo in the treatment of OCD, and social phobia, separation anxiety disorder or GAD in well controlled trials in paediatric patients. Reductions in symptoms of anxiety with fluvoxamine have been observed for up to 1 year in children and adolescents with OCD. However, there are currently no comparative trials of fluvoxamine with other pharmacological agents. In the absence of such trials, current consensus opinion recommends that when pharmacotherapy is indicated, fluvoxamine, like other SSRIs, can be used as first-line treatment for anxiety disorders, particularly OCD, in paediatric patients. However, direct comparisons are required to assess the relative efficacy and tolerability of pharmacological agents in order to make firm recommendations for the treatment of anxiety disorders in this patient group.     

Fluvoxamine in the treatment of the older depressed patient; double-blind, placebo-controlled data

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

Fluvoxamine augmentation in chronic schizophrenia: An open exploratory study

The effect of augmenting standard antipsychotic treatment with the specific serotonergic reuptake inhibitor (SSRI) fluvoxamine was examined in severely disabled chronic schizophrenic inpatients using an open, naturalistic protocol. Fluvoxamine in doses ranging from 25 to 200 mg was added to the antipsychotic medication which was kept constant. Patients were followed for the duration of treatment (to date up to 7·5 months). Assessment included BPRS SANS SAPS and CGI scales (CGI only in the most severely disturbed), and global impressions of occupational and social functioning. Fourteen (74%) of the 19 patients studied showed improvement using 15 per cent change in SANS score or CGI improvement score > = 1 as criterion. The symptom constellation appeared to influence the rate and timing of response. Ten patients experienced exacerbations, some within 2 months of starting treatment, others after 5–6 months. The findings suggest that SSRI augmentation may be effective in severely disabled schizophrenics.     

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.     

Placebo-controlled, double-blind study of the effects of proglumide in the treatment of schizophrenia.

A double-blind, placebo-controlled, randomized study was performed to determine whether proglumide added to ongoing neuroleptic medication was efficacious in the treatment of 32 patients with persistent positive and negative schizophrenic symptoms. Patients treated with both proglumide and placebo showed a significant improvement over the 8 weeks of the study, but no significant difference between the patients taking proglumide and those taking placebo could be demonstrated. In addition, proglumide had no effect on plasma homovanillic acid concentrations or neuroleptic drug activity. The results suggest that, at least for the dose of proglumide used in this study (15 mg/day), the addition of this particular cholecystokinin antagonist does not potentiate the antipsychotic efficacy of neuroleptic medication in patients with persistent schizophrenic symptoms.     

Deprenyl augmentation for treating negative symptoms of schizophrenia: a double-blind, controlled study

Augmentation of dopaminergic neurotransmission has been suggested as a treatment strategy for negative symptoms of schizophrenia. On the basis of open studies that reported the potential benefit of deprenyl (selegiline) as augmentation to antipsychotic treatment, this double-blind, controlled study was designed to further address this question. Sixteen schizophrenic patients with predominately negative symptoms, manifesting clinical stability on maintenance antipsychotic treatment, were randomly assigned to receive either deprenyl 15 mg/day or placebo in addition to their antipsychotic treatment for 8 weeks. Clinical follow-up and ratings were done during this period and for 8 more weeks after deprenyl discontinuation. Both groups showed a statistically significant but clinically marginal improvement over the 8 weeks of deprenyl or placebo treatment. This improvement was abolished during the postdiscontinuation follow-up period. Deprenyl at a dose of 15 mg/day did not offer therapeutic benefit in our patients. A significant placebo effect was observed, which may be the result of increased patient-doctor contact during the study.     

The onset and time course of response of negative symptoms to add-on fluvoxamine treatment

Not enough is known about the propensity of individual negative symptoms to respond to treatment and the dynamics of this change. We have previously shown that adding the selective serotonin reuptake inhibitor fluvoxamine to antipsychotics can improve negative symptoms, and now provide data on the response of individual negative symptoms to such treatment. We examined items on the Schedule for the Assessment of Negative Symptoms for patients participating in two published controlled studies comparing the effect of add-on fluvoxamine and placebo on negative symptoms. Using a mixed regression model, we analysed item scores at each week of the study to identify the first signs of a treatment effect. Potential confounding effects of depressive extrapyramidal and positive symptoms were statistically controlled. Eleven of 16 items tested showed improvement, five within 2 weeks and a further four within 3 weeks of starting treatment. The most rapidly responding items included core negative symptoms such as alogia. The propensity for and rate of improvement with fluvoxamine treatment differs for the various negative symptoms. Many symptoms, including those generally agreed to be core features of the illness such as alogia, improved within 2-3 weeks of treatment initiation.     

Effect of fluvoxamine on plasma risperidone concentrations in patients with schizophrenia

The effect of fluvoxamine on plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) was investigated in 11 schizophrenic patients with prevailingly negative or depressive symptoms. Additional fluvoxamine, at the dose of 100 mg/day, was administered for 4 weeks to patients stabilized on risperidone (3-6 mg/day). Mean plasma concentrations of risperidone, 9-OH-risperidone and the active moiety (sum of the concentrations of risperidone and 9-OH-risperidone) were not significantly modified following co-administration with fluvoxamine. After 4 weeks, fluvoxamine dosage was increased to 200 mg/day in five patients and then maintained until the end of week 8. At final evaluation, mean plasma levels of risperidone active moiety were not modified in the six patients who were still receiving the initial fluvoxamine dose, while concentrations increased slightly but significantly (by a mean 26% over pretreatment; P < 0.05) in the subgroup of five subjects treated with a final dose of 200 mg/day. Fluvoxamine co-administration with risperidone was well tolerated and no patient developed extrapyramidal side effects. These findings indicate that fluvoxamine at dosages up to 100 mg/day is not associated with clinically significant changes in plasma risperidone concentrations. However, higher doses of fluvoxamine may elevate plasma risperidone levels, presumably as a result of a dose-dependent inhibitory effect of fluvoxamine on CYP2D6-and/or CYP3A4-mediated 9-hydroxylation of risperidone.     

The effect of augmentation with moclobemide on symptoms of schizophrenia.

The effectiveness of adding moclobemide to antipsychotic treatment in schizophrenic patients with prominent negative symptoms was examined. Eleven chronic schizophrenic patients had their regular antipsychotic treatment augmented by the addition of moclobemide 450 mg/day for 8 weeks. A significant improvement was seen on the Positive and Negative Syndrome Scale (PANSS) negative factor and for the Scale for the Assessment of Negative Symptoms (SANS) scores, PANSS total score, PANSS general factor score and Hamilton Depression Scale scores. Positive symptoms were not altered. Moclobemide augmentation may ameliorate negative, depressive and general symptoms in schizophrenia.     

Fluvoxamine treatment of generalized social anxiety disorder in Japan: a randomized double-blind, placebo-controlled study

The efficacy of selective serotonin reuptake inhibitors (SSRIs) for the treatment of social anxiety disorder (SAD) has been reported in the USA and Europe. However, no clinical investigation has been done with SSRIs in Japanese patients with SAD. This study was performed to determine the effectiveness and safety of fluvoxamine for generalized SAD (GSAD) in Japanese patients. In this double-blind study, patients meeting DSM-IV criteria for GSAD were randomized to receive treatment with fluvoxamine or placebo for 10 wk. Fluvoxamine treatment was initiated at 50 mg/d, and increased by 50 mg weekly to a maximum of 150 or 300 mg/d. The primary efficacy outcome was mean change from baseline on the Liebowitz Social Anxiety Scale - Japanese Version (LSAS-J) total score. The secondary outcomes were response according to the Clinical Global Impressions - Global Improvement (CGI-I) score and three domains of the Sheehan Disability Scale (SDS; used to assess psychosocial impairment). A total of 176 fluvoxamine-treated patients and 89 placebo-treated patients were eligible for the efficacy analysis. At week 10, the fluvoxamine-treated patients had a significantly greater reduction in the LSAS-J total score compared with placebo-treated patients (p=0.0197), with significantly more fluvoxamine recipients being at least much improved on the CGI-I scale compared with placebo-treated patients (p=0.024). Fluvoxamine-treated patients also had better responses on the SDS compared with placebo-treated patients (p=0.0208). Fluvoxamine was safe and well tolerated. These results suggest that fluvoxamine is effective for the treatment of Japanese patients with GSAD.     

Selective serotonin re-uptake inhibitor augmentation in the treatment of negative symptoms of schizophrenia

Negative symptoms are core features of schizophrenia that respond poorly to first-generation antipsychotics and present a major obstacle in rehabilitation. Patients may be somewhat more responsive to clozapine and second-generation antipsychotics but even then, considerable impairment remains. This paper reviews the use of selective serotonin re-uptake inhibitor (SSRI) augmentation of antipsychotics in the treatment of negative symptoms in schizophrenia. Important methodological issues particular to the study of negative symptoms are also discussed. Current evidence indicates that at least two SSRIs, fluvoxamine and fluoxetine, can ameliorate primary negative symptoms in chronic schizophrenic patients treated with first-generation antipsychotics. Onset of improvement may be detected within 2 weeks of starting treatment. The combination is well-tolerated, although as antipsychotic drug concentrations may rise, close monitoring of drug doses and possibly drug concentrations is needed. So far, evidence regarding SSRI augmentation of second-generation antipsychotics is limited and in view of the increasing use of these newer agents, controlled studies are urgently needed. SSRI augmentation may be a useful addition to the treatment of schizophrenic patients with persistent negative symptoms. The paradoxical findings that both clozapine, a serotonin antagonist, and an SSRI antidepressant added to antipsychotics, can improve negative symptoms suggests that these pharmacologically distinct treatments may share common final mechanisms. A better understanding of these mechanisms can shed light on the pathogenesis of negative symptoms and provide new targets for drug development.     

Fluvoxamine as an adjunctive agent in schizophrenia

Schizophrenia is a common mental disorder that has an early onset and rates high as a cause of medical disability. Antipsychotic agents are the mainstay of treatment but response is often inadequate. Negative symptoms (disturbances in volition, social interaction and affective functions) are particularly difficult to treat and form a major obstacle to rehabilitation. A promising approach to improve response of negative symptoms has been to add a selective serotonin reuptake inhibitor (SSRI) antidepressant to antipsychotic treatment. This review examines evidence pertaining to the efficacy, tolerability, and safety of the SSRI fluvoxamine, combined with antipsychotic agents, in the treatment of negative symptoms in schizophrenia. Important methodological issues, such as differentiating primary and secondary negative symptoms, are discussed. The balance of available evidence indicates that fluvoxamine can improve primary negative symptoms in chronic schizophrenia patients treated with typical antipsychotics and suggests that it may also do so in some patients treated with clozapine. This combination is generally safe and well tolerated although, as antipsychotic drug concentrations may be elevated, attention to dose and drug monitoring should be considered appropriately. Combination with clozapine may require particular caution because of potential toxicity if serum clozapine levels rise steeply. The fluvoxamine doses effective in augmentation are lower than those usually used to treat depression. Evidence regarding the use of fluvoxamine augmentation to treat phenomena, such as obsessions and aggression, which may be associated with schizophrenia, is also examined. An important goal of future studies will be to define which patient groups can benefit from combined treatment.     

Treatment of Alcoholic Organic Brain Syndrome with the Serotonin Reuptake Inhibitor Fluvoxamine:

The chronic effects of fluvoxamine (200 mg per day for 4 weeks) were studied in ten alcoholic organic brain syndrome patients in a double-blind cross-over design. Complete neuropsychological evaluation was performed as well as measurement of neurochemical changes in CSF. Fluvoxamine produced a small but significant improvement in memory performance. An analysis of fluvoxamine minus placebo difference scores showed a significant correlation between memory functioning and CSF 5HIAA levels. Alcohol amnestic syndrome patients who had the highest blood levels of fluvoxamine demonstrated the largest changes in CSF 5HIAA and improvement in memory performance under fluvoxamine. These findings implicate a role of serotonergic mechanisms in alcoholic organic brain syndrome and suggest that with individual titration of the drug dose, fluvoxamine might be a clincally useful agent in the treatment of this syndrome.     

Selective serotonin re-uptake inhibitor augmentation in the treatment of negative symptoms of schizophrenia

Negative symptoms are core features of schizophrenia that respond poorly to first-generation antipsychotics and present a major obstacle in rehabilitation. Patients may be somewhat more responsive to clozapine and second-generation antipsychotics but even then, considerable impairment remains. This paper reviews the use of selective serotonin re-uptake inhibitor (SSRI) augmentation of antipsychotics in the treatment of negative symptoms in schizophrenia. Important methodological issues particular to the study of negative symptoms are also discussed. Current evidence indicates that at least two SSRIs, fluvoxamine and fluoxetine, can ameliorate primary negative symptoms in chronic schizophrenic patients treated with first-generation antipsychotics. Onset of improvement may be detected within 2 weeks of starting treatment. The combination is well-tolerated, although as antipsychotic drug concentrations may rise, close monitoring of drug doses and possibly drug concentrations is needed. So far, evidence regarding SSRI augmentation of second-generation antipsychotics is limited and in view of the increasing use of these newer agents, controlled studies are urgently needed. SSRI augmentation may be a useful addition to the treatment of schizophrenic patients with persistent negative symptoms. The paradoxical findings that both clozapine, a serotonin antagonist, and an SSRI antidepressant added to antipsychotics, can improve negative symptoms suggests that these pharmacologically distinct treatments may share common final mechanisms. A better understanding of these mechanisms can shed light on the pathogenesis of negative symptoms and provide new targets for drug development.     

A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of generalized social anxiety disorder

This was a randomized double-blind placebo-controlled multicenter study to assess the efficacy, safety, and tolerability of fluvoxamine in a controlled release (CR) formulation for treatment of generalized social anxiety disorder (GSAD). A total of 300 subjects with GSAD were randomly assigned to receive either fluvoxamine CR (N = 149) or placebo (N = 151) for 12 weeks. Mean changes from baseline to end point in Liebowitz Social Anxiety Scale (LSAS), Clinical Global Impression Severity of Illness Scale (CGI-S), Sheehan Disability Scale (SDS), as well as the mean end point scores in Clinical Global Impression Improvement Scale (CGI-I) and Patient Global Impression of Improvement Scale (PGI) were compared between the fluvoxamine CR and placebo treatment groups. Arizona Sexual Experience Scale (ASEX), adverse event, and other safety parameters were also assessed. The results demonstrated that fluvoxamine CR was significantly superior to placebo in decreasing LSAS total score (primary measure) starting at week 4. At end point, there was a mean change from baseline of -36.1 +/- 2.7 (37% reduction) in the LSAS total score in the fluvoxamine CR group compared with -27.3 +/- 2.4 (28% reduction) in the placebo group (P = 0.020 for mean change). Fluvoxamine CR was also significantly superior to placebo in SDS, CGI-S, CGI-I at end point (secondary measures). When compared with placebo, fluvoxamine CR did not cause any significant weight gain or clinically significant sexual dysfunction as measured by ASEX. In summary, fluvoxamine CR is an efficacious, safe, and well-tolerated treatment of generalized social anxiety disorder.     

Differential effects of high-dose amisulpride versus flupentixol on latent dimensions of depressive and negative symptomatology in acute schizophrenia: an evaluation using confirmatory factor analysis

While many acutely ill schizophrenic patients suffer from depressive symptoms, most studies on the efficacy of antipsychotic drugs focus on positive and negative symptoms. Dimensional models of schizophrenic symptoms, based on confirmatory factor analysis (CFA) using structural equation modelling, offer a methodological alternative to compare antipsychotics on empirically justified latent factors. The present report is a refined analysis of a published double-blind study on the D2/D3-selective antagonist amisulpride (ASP) versus the mixed D1-5/5-HT2 antagonist flupentixol (FPX). CFA was applied to Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Bech-Rafaelsen Melancholia Scale and Simpson-Angus Scale subscores to examine differential effects of high doses of ASP and FPX on negative and depressive symptom dimensions in 126 acutely ill schizophrenic patients. A four-factor model comprising the full spectrum of acute symptomatology and a three-factor model ('negative', 'anhedonia-apathy', 'depressive') restricted to negative and depressive symptoms were yielded with an identical 'depressive' dimension in both models. Analyses of CFA-derived factor scores showed that ASP was significantly superior to FPX regarding the latent 'depressive' dimension, independent of baseline scores, dosage and changes in akinesia. Neither the negative' dimension nor 'anhedonia-apathy' showed significantly different treatment effects. CFA-based analyses appear to be suitable for psychotropic drug evaluation when more refined and data-related information on drug efficacy profiles are required.