Augmentation of antipsychotic drug action by azapirone 5-HT1A receptor partial agonists: a meta-analysis

The aim of the study was to evaluate the evidence that serotonin1A (5-HT1A) receptor partial agonists of the azapirone class, which are not antipsychotic, have benefits for adjunctive treatment of overall psychopathology, positive and negative symptoms for patients with schizophrenia. We carried out a systematic review of the literature available through PubMed, Cochrane Library, PsycINFO and Google Scholar during September 2012, followed by a meta-analysis of randomized placebo-controlled trials. Risk ratio (RR), 95% confidence intervals (CI) and standardized mean difference (s.m.d.) were calculated. Four studies, involving 163 patients with schizophrenia, met inclusion criteria: buspirone: three trials and 137 patients; tandospirone: one trial and 26 patients. As adjunctive therapy, 5-HT1A partial agonists were significantly superior to placebo for overall improvement in psychopathology (s.m.d. = -0.46, CI = -0.79 to -0.13, p = 0.006, N = 4, n = 149) and marginally more effective to improve positive symptoms (s.m.d. = -0.31, CI = -0.64 to 0.01, p = 0.06, N = 4, n = 149). However, 5-HT1A partial agonists were not more efficacious than placebo as adjunctive therapy for improving negative symptoms (s.m.d. = -0.09, CI = -0.60 to 0.42, p = 0.72, N = 4, n = 149). In addition, there was no significant difference in discontinuation rates between 5-HT1A partial agonists and placebo (all cause: RR = 0.98, CI = 0.49-1.98, p = 0.96, N = 4, n = 153, side-effects: RR = 1.96, CI = 0.54-7.19, p = 0.31, N = 4, n = 153). 5-HT1A partial agonists as adjunctive therapy improved overall psychopathology with a trend to improve positive symptoms in patients with schizophrenia. Because the number of studies was small, additional controlled clinical trials with larger numbers of patients are indicated.