BACKGROUNDPerospirone is a second-generation antipsychotic (SGA) used only in Japan, and acts as a serotonin (5-HT)1A receptor partial agonist, 5-HT2A receptor inverse agonist, and dopamine (D)₂, D₄, and α₁-adrenergic receptor antagonist. To our knowledge, no meta-analysis addressing the efficacy and effectiveness of perospirone in schizophrenia has been published to date.OBJECTIVEThe aim of the study was to identify the characteristics of perospirone by assessing the efficacy, discontinuation rate, and side effects of perospirone versus other antipsychotics in the treatment of patients with schizophrenia.METHODSUsing information obtained from the PubMed, PsycINFO, Google Scholar and Cochrane Library databases without language restrictions published up to 10 June 2013, we conducted a systematic review and meta-analysis of patient data from randomized controlled trials comparing perospirone with other antipsychotic medications. Risk ratio (RR), standardized mean difference (SMD) and 95% confidence intervals were calculated. All studies used the Positive and Negative Syndrome Scale (PANSS) for the evaluation of the schizophrenia psychopathology.RESULTSThe search in PubMed, Cochrane Library databases, Google Scholar and PsycINFO yielded 69 hits. We included three studies in the current meta-analysis and excluded 66 studies based on title, abstract, and full text review. Moreover, two additional studies were identified from a review article. Across the five studies (mean duration 9.6 weeks), 562 adult patients with schizophrenia were randomized to perospirone (n = 256), olanzapine (n = 20), quetiapine (n = 28), risperidone (n = 53), aripiprazole (n = 49), haloperidol (n = 75), or mosapramine (n = 81). Perospirone was not different from other pooled antipsychotics regarding reduction in PANSS negative (SMD = 0.38, p = 0.09) and general (SMD = 0.28, p = 0.06) subscale scores, and discontinuation due to any cause (RR = 1.03, p = 0.83), inefficacy (RR = 0.99, p = 0.98) and side effects (RR = 0.72, p = 0.25). However, perospirone was inferior to other pooled antipsychotics in the reduction of PANSS total scores (SMD = 0.36, p = 0.04) and positive subscale scores (SMD = 0.34, p = 0.03). Moreover, excluding the comparison of perospirone with the first-generation antipsychotic (haloperidol), perospirone was inferior to other pooled SGAs in the reduction of PANSS total scores (SMD = 0.46, p = 0.02), positive (SMD = 0.42, p = 0.03), negative (SMD = 0.52, p = 0.02) and general subscale scores (SMD = 0.37, p = 0.03). However, perospirone was superior to haloperidol in the reduction of PANSS negative subscale scores (SMD = -0.41, p = 0.01). Perospirone also had lower scores related to extrapyramidal symptoms than other pooled antipsychotics (SMD = -0.30, p = 0.01).CONCLUSIONSOur results suggest that although perospirone seems to be a well tolerated treatment, perospirone does not reduce PANSS score as much as other SGAs.