The International Journal of Neuropsychopharmacology

Research Article

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

Taro Kishia1 c1, Herbert Y. Meltzera2 and Nakao Iwataa1

a1 Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

a2 Division of Psychiatry and Behavioural Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA


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.

(Received January 11 2013)

(Revised January 11 2013)

(Accepted January 31 2013)

(Online publication April 03 2013)

Key words

  • 5-HT1A receptor partial agonist;
  • buspirone;
  • discontinuation rate;
  • efficacy;
  • meta-analysis;
  • psychosis;
  • schizophrenia;
  • systematic review;
  • tandospirone