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. 2016 Dec 15:12:3221-3236.
doi: 10.2147/NDT.S125367. eCollection 2016.

Efficacy and tolerability of topiramate-augmentation therapy for schizophrenia: a systematic review and meta-analysis of randomized controlled trials

Yuji Okuyama  1 , Kazuto Oya  1 , Shinji Matsunaga  1 , Taro Kishi  1 , Nakao Iwata  1
Affiliations

Efficacy and tolerability of topiramate-augmentation therapy for schizophrenia: a systematic review and meta-analysis of randomized controlled trials

Yuji Okuyama et al. Neuropsychiatr Dis Treat. .

Abstract

This study aimed to perform a comprehensive meta-analysis of topiramate-augmentation therapy in patients with schizophrenia receiving antipsychotic agents. Data published up to June 20, 2016 were obtained from the PubMed, PsycINFO, and Cochrane Library databases. Twelve randomized controlled trials comparing topiramate to placebo or antipsychotic only were included (n=676 patients). The primary outcome was change in overall symptoms. Relative risk (RR) and standardized mean difference (SMD), along with 95% confidence intervals, were calculated using random effects model for each outcome. Topiramate-augmentation therapy was superior to the control for decreasing overall symptoms (SMD -0.55, 95% confidence interval -0.86 to -0.24; P=0.001; I2=55%, eight comparisons, n=380), positive symptoms (SMD -0.4), negative symptoms (SMD -0.47), and Positive and Negative Syndrome Scale general subscale scores (SMD -0.67). Furthermore, topiramate-augmentation therapy decreased weight (SMD -0.69) and body mass index (SMD -0.95) compared with the control. Topiramate was similar to the control with respect to discontinuation due to all causes (RR 1.19), inefficacy (RR 1.71), and adverse events (RR 1.09). Topiramate was associated with higher incidence of paresthesia (RR 2.67) and attention difficulty (RR 8.97) compared with the control. Our results seemed to suggest that topiramate-augmentation therapy improves the psychopathology of schizophrenia with good tolerability and has the additional advantage of weight maintenance. However, because there were some limitations (numbers of studies and patients included in the meta-analysis were small, some studies used completer analysis, Chinese studies were included in the meta-analysis, and studies that had a risk of bias were included in the meta-analysis) in this study, we cannot apply the results of this study in daily clinical practice.

Keywords: efficacy; meta-analysis; safety; schizophrenia; systematic review; topiramate.

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Conflict of interest statement

The authors report no conflicts of interest in this work, but report the following interests: Dr Okuyama has received speaker’s honoraria from Janssen; Dr Oya has received honoraria from Eisai, Eli Lilly, Janssen, Meiji, Otsuka, and Tanabe-Mitsubishi; Dr Matsunaga has received honoraria from Eisai, Janssen, Novartis, Daiichi Sankyo, Ono, Eli Lilly, Takeda, and Otsuka and has a Fujita Health University School of Medicine research grant and Grant-in-Aid for Young Scientists (B); Dr Kishi has received speaker’s honoraria from Abbvie, Astellas, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Yoshitomi, Otsuka, Meiji, Mochida, Shionogi, Tanabe-Mitsubishi, Tsumura, Novartis, and Pfizer and has a Fujita Health University School of Medicine research grant and Grant-in-Aid for Young Scientists (B); and Dr Iwata has received honoraria from Astellas, Dainippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Yoshitomi, Otsuka, Meiji, Shionogi, Novartis, and Pfizer.

Figures

Figure 1
Figure 1
Literature search results. Abbreviation: RCT, randomized controlled trial.
Figure 2
Figure 2
Forest plots of psychopathological outcomes. Abbreviations: SMD, standardized mean difference; CI, confidence interval; TOP, topiramate; CON, control.
Figure 3
Figure 3
Forest plots of psychopathological and anthropometric outcomes. Abbreviations: PANSS, Positive and Negative Syndrome Scale; SMD, standardized mean difference; CI, confidence interval; TOP, topiramate; CON, control; BMI, body mass index.
Figure 4
Figure 4
Forest plots of individual adverse events. Abbreviations: CI, confidence interval; TOP, topiramate; CON, control.
Figure 5
Figure 5
Forest plots of individual adverse events. Abbreviations: CI, confidence interval; TOP, topiramate; CON, control.
See this image and copyright information in PMC

References

    1. Afshar H, Roohafza H, Mousavi G, et al. Topiramate add-on treatment in schizophrenia: a randomised, double-blind, placebo-controlled clinical trial. J Psychopharmacol. 2009;23(2):157–162. - PubMed
    1. Behdani F, Hebrani P, Ardani AR, Rafee E. Effect of topiramate augmentation in chronic schizophrenia: a placebo-controlled trial. Arch Iran Med. 2011;14(4):270–275. - PubMed
    1. Chen ZX, Xia ML, Xia WJ, Huang HG, Jin L. Topiramatefor prevention of olanzapine associated weight gain. Modern Pract Med. 2012;24:979–980. Chinese.
    1. Chengappa KN, Kupfer DJ, Parepally H, et al. A placebo-controlled, random-assignment, parallel-group pilot study of adjunctive topiramate for patients with schizoaffective disorder, bipolar type. Bipolar Disord. 2007;9(6):609–617. - PubMed
    1. Kim JH, Yim SJ, Nam JH. A 12-week, randomized, open-label, parallel-group trial of topiramate in limiting weight gain during olanzapine treatment in patients with schizophrenia. Schizophr Res. 2006;82(1):115–117. - PubMed

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