title: Selective serotonin 3 receptor antagonist treatment for schizophrenia: meta-analysis and systematic review.
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.
authors.affiliation: Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, 470-1192, Japan, tarok@fujita-hu.ac.jp.
authors.forename: Taro
authors.initials: T
authors.lastname: Kishi
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Mukai
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Nakao
authors.initials: N
authors.lastname: Iwata
mesh_terms: D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003248:Constipation / Q000139:chemically induced; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D017829:Granisetron / Q000009:adverse effects / Q000627:therapeutic use; D006220:Haloperidol / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use; D009325:Nausea / Q000139:chemically induced; D017294:Ondansetron / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000502:physiology; D018967:Risperidone / Q000008:administration & dosage / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D063189:Symptom Assessment; D016896:Treatment Outcome; D000077526:Tropisetron; D014839:Vomiting / Q000139:chemically induced
chemical_list: D014150:Antipsychotic Agents; D017829:Granisetron; D006220:Haloperidol; D007211:Indoles; D017294:Ondansetron; D044406:Receptors, Serotonin, 5-HT3; D018967:Risperidone; D058831:Serotonin 5-HT3 Receptor Antagonists; D000077526:Tropisetron
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