Efficacy for Psychopathology and Body Weight and Safety of Topiramate-Antipsychotic Cotreatment in Patients With Schizophrenia Spectrum Disorders: Results From a Meta-Analysis of Randomized Controlled Trials.

Abstract

OBJECTIVE:

To meta-analyze the efficacy and tolerability of topiramate-antipsychotic cotreatment in schizophrenia.

DATA SOURCES:

PubMed/MEDLINE database were searched until September 5, 2015, using the keywords topiramate AND antipsych* OR neurolept* OR specific antipsychotic names.

STUDY SELECTION:

Randomized controlled trials (RCTs) of topiramate-antipsychotic cotreatment versus placebo and ongoing antipsychotic treatment in patients with schizophrenia spectrum disorders were included.

DATA EXTRACTION:

Two evaluators extracted data. Standardized mean difference (SMD), weighted mean difference (WMD), and risk ratio (RR) ± 95% CIs were calculated.

RESULTS:

In 8 RCTs, lasting a mean ± SD of 13.6 ± 4.9 weeks, 439 patients were randomized to topiramate (100-400 mg/d) versus placebo (trials = 7) or ongoing antipsychotic treatment (trial = 1). Topiramate outperformed the comparator regarding total psychopathology (trials = 6, n = 269, SMD = -0.57 [95% CI, -1.01 to -0.14], P = .01), positive symptoms (trials = 4, n = 190, SMD = -0.56 [95% CI, -1.0 to -0.11], P = .01), negative symptoms (trials = 4, n = 190, SMD = -0.62 [95% CI, -1.13 to -0.10], P = .02) general psychopathology (trials = 3, n = 179, SMD = -0.69 [95% CI, -1.27 to -0.11], P = .02), body weight (trials = 7, n = 327, WMD = -3.14 kg [95% CI, -5.55 to -0.73], P = .01), and body mass index (BMI) (trials = 4, n = 198, WMD = -1.80 [95% CI, -2.77 to -0.84], P = .0003). Topiramate's efficacy for total psychopathology and weight reduction effects were not mediated/moderated by trial duration, topiramate dose, sex, age, inpatient status, baseline Positive and Negative Syndrome Scale, or baseline BMI. Conversely, clozapine-topiramate cotreatment moderated greater efficacy, but less weight loss, compared to topiramate-nonclozapine antipsychotic combinations. All-cause discontinuation was similar between topiramate and control groups (trials = 7, RR = 1.24 [95% CI, 0.76 to 2.02], P = .39). Topiramate trended only toward more paresthesia than placebo (trials = 4, RR = 2.03 [95 % CI, 0.99 to 4.18], P = .05).

CONCLUSIONS:

Topiramate-antipsychotic cotreatment significantly reduced total, positive, negative, and general psychopathology and weight/BMI in patients with schizophrenia spectrum disorder while being well tolerated. However, larger studies are needed to confirm and extend these findings.

• Authors: Christoph U Correll, Lawrence Maayan, John Kane, Marc De Hert, Dan Cohen
• Journal: The Journal of clinical psychiatry (J Clin Psychiatry) Vol. 77 Issue 6 Pg. e746-56 (06 2016) ISSN: 1555-2101 [Electronic] United States
• PMID: 27337425 (Publication Type: Journal Article, Meta-Analysis)
• Copyright: © Copyright 2016 Physicians Postgraduate Press, Inc.

Chemical References

• Antipsychotic Agents
• Topiramate
• Fructose

Topics

• Antipsychotic Agents (adverse effects, therapeutic use)
• Body Weight (drug effects)
• Drug Therapy, Combination
• Fructose (adverse effects, analogs & derivatives, therapeutic use)
• Humans
• Odds Ratio
• Psychiatric Status Rating Scales (statistics & numerical data)
• Psychometrics
• Psychopathology
• Randomized Controlled Trials as Topic
• Schizophrenia (drug therapy)
• Schizophrenic Psychology
• Topiramate
• Treatment Outcome