Abstract
Double-blinded, randomized, placebo-control trials of selective serotonin 3 receptor antagonists (5-HT3R-ANTs) for schizophrenia have differed in outcome. This meta-analysis tests the hypothesis that 5-HT3R-ANTs are effective for the treatment for schizophrenia. We searched PubMed, the Cochrane Library database, and PsycINFO up to June 15, 2013. We conducted a systematic review and meta-analysis of individual patient data from randomized controlled trials comparing 5-HT3R-ANTs add-on therapy with placebo. The risk ratio (RR), 95 % confidence intervals (CI), and standardized mean difference (SMD) were calculated. A random-effects model was used. Six studies (total n = 311) were identified. These included one granisetron plus risperidone study, one ondansetron plus risperidone study, one ondansetron plus haloperidol, and three tropisetron plus risperidone studies. The statistically significant effects of 5-HT3R-ANTs add-on therapy on Positive and Negative Syndrome Scale (PANSS) total scores were SMD = −1.03, CI = −1.70 to −0.36, p = 0.003 (I 2 = 82 %, 5 studies, n = 261); on negative scores were SMD = −1.10, CI = −1.82 to −0.39, p = 0.002 (I 2 = 84 %, 5 studies, n = 261); and on PANSS general scores were SMD = −0.70, CI = −1.23 to −0.17, p = 0.01 (I 2 = 73 %, 5 studies, n = 261). However, 5-HT3R-ANTs add-on therapy was not superior to placebo in PANSS positive scores (SMD = −0.12, p = 0.33). Dropout due to all cause (RR = 0.80, p = 0.50), inefficacy (RR = 0.76, p = 0.65), or adverse events (RR = 0.84, p = 0.75) was similar in both groups. Constipation occurred significantly more often with 5-HT3R-ANTs than placebo (RR = 2.05, CI = 1.07–3.91, p = 0.03, NNH = 11, p = 0.02). 5-HT3R-ANTs add-on therapy is more beneficial on the psychopathology (especially negative symptoms) than controls in patients with schizophrenia, and 5-HT3R-ANTs seem to be well-tolerated treatments.
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Acknowledgments
Dr. Kishi has received speaker’s honoraria from Abbott, Astellas, Daiichi Sankyo, Dainippon Sumitomo, Eli Lilly, GlaxoSmithKline, Yoshitomi, Otsuka, Meiji, Shionogi, Janssen, Novartis, Tanabe-Mitsubishi, and Pfizer. Dr. Iwata has received speaker’s honoraria from Astellas, Dainippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Yoshitomi, Otsuka, Meiji, Shionogi, Novartis, and Pfizer.
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All authors declare that they have no direct conflict of interest relevant to this study. No grant support or other sources of funding were used to conduct this study or prepare this article.
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Kishi, T., Mukai, T., Matsuda, Y. et al. Selective Serotonin 3 Receptor Antagonist Treatment for Schizophrenia: Meta-analysis and Systematic Review. Neuromol Med 16, 61–69 (2014). https://doi.org/10.1007/s12017-013-8251-0
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DOI: https://doi.org/10.1007/s12017-013-8251-0