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

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.