Efficacy of Adjunctive Treatments Added to Olanzapine or Clozapine for Weight Control in Patients with Schizophrenia: A Systematic Review and Meta‐Analysis

Abstract

Objectives. This study was conducted to review systematically adjunctive treatments for weight reduction in patients with schizophrenia and compare efficacies of clinical trials through meta-analysis, so as to provide effective clinical guideline regarding weight control for patients taking atypical antipsychotics. Methods. Candidate clinical trials were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, and PsycINFO. Fourteen randomized clinical trials were included for systematic review and meta-analysis from 132 potential trials. The Comprehensive Meta-Analysis version 2 was used for meta-analysis. Results. Difference in means and significances from meta-analyses regarding weight control by adjunctive treatments showed that topiramate, aripiprazole, or sibutramine was more effective than metformin or reboxetine. Psychiatric evaluations did not show statistically significant changes between treatment groups and placebo groups except topiramate adjunctive treatments. Adverse effects regarding adjunctive therapies were tolerable and showed statistically no significances compared to control groups. Conclusion. Though having several reports related to exacerbation of psychiatric symptoms, topiramate and aripiprazole are more efficacious than other medications in regard to weight reduction and less burden of critical adverse effects as well as being beneficial for clinical improvement.

Efficacy and safety of adjunctive topiramate for schizophrenia: a meta‐analysis of randomized controlled trials

“…By adding more evidence, our review found a more optimistic view of topiramate augmentation in attenuating psychotic symptoms than prior meta‐analyses in that effect size estimates were more robust with much more narrow 95% CIs throughout and in that effect sizes generalized to clozapine and non‐clozapine antipsychotics as well as across a number of other relevant design, patient, and illness variables. Furthermore, our meta‐analysis confirmed the benefits of topiramate augmentation for weight reduction/slowing of weight gain, consistent with the prior reviews and meta‐analyses . However, the prior reviews and meta‐analyses had been limited by the much smaller number of studies, fewer participants, and by the lack of inclusion of all the metabolic variables, ADRs, and non‐clozapine antipsychotics, as well as by a lack of quality/risk of bias assessment, and relevant subgroup and meta‐regression analyses.…”

“…Topiramate's efficacy for improving psychopathology and/or reducing body weight in antipsychotic‐treated patients with schizophrenia has been explored in prior meta‐analyses , but the number of studies and their power were limited. Even the most recent and largest meta‐analysis included only 8 RCTs (6 reporting on efficacy and 7 reporting data on weight reduction).…”

Outcomes and safety of concomitant topiramate or metformin for antipsychotics-induced obesity: A randomized controlled trial

“…To be sure, the recurrence or worsening of illness in some outpatients was completely due to non-compliance for the antipsychotic treatment during the trial, it was not associated with the concomitant use of topiramate or metformin although it was not consistent with Choi et al report. 33 As to topiramate on maintaining stability in schizophrenia or affective disorders, in this study, only three cases of psychiatric symptoms worsen were found in the topiramate and metformin group after the end of this study, no signi cant difference was found between the two groups. So, there is not enough evidence that topiramate might stabilize the illness of schizophrenia and affective disorders according to this results.…”

Adjunctive Reboxetine for Schizophrenia: Meta-analysis of Randomized Double-blind, Placebo-controlled Trials

“…The efficacy of reboxetine in treating negative symptoms and/ or reducing AP-induced weight gain in schizophrenia have been examined in meta-analyses [10,12,[31][32][33][34]. Common limitations of these meta-analyses include the small number of included studies, resulting in insufficient power.…”

“…Common limitations of these meta-analyses include the small number of included studies, resulting in insufficient power. For example, 3 meta-analyses [12,33,34], each with 2 RCTs (n = 85) [18,22], found that reboxetine was superior to placebo in reducing AP-induced weight gain. Another meta-analysis [31] included 9 RCTs, but one of them was an open-label study [35], the inclusion of which violated standard recommendations [36].…”