Effect of 5-HT(1A) Receptor Partial Agonists of the Azapirone Class as an Add-On Therapy on Psychopathology and Cognition in Schizophrenia: A Systematic Review and Meta-Analysis

BACKGROUND: There are ongoing efforts to examine the effect of 5-HT(1A) receptor partial agonists as an add-on therapy for several symptoms of schizophrenia. By conducting a systematic review and meta-analysis, we evaluated whether augmentation with 5-hydroxtrypatamine (5-HT)(1A) partial agonists of the azapirone class improves psychotic symptoms and attention/processing speed, a key domain of cognition, in patients with schizophrenia. METHODS: A literature search was performed from 1987 to February 25, 2022, to identify randomized controlled trials. The standardized mean difference (SMD) with 95% confidence intervals (CI) was calculated when there were 2 or more studies. Seven studies, involving 435 patients, met the inclusion criteria. RESULTS: Random-effects model meta-analyses revealed that add-on therapy with buspirone or tandospirone had a significant beneficial effect on overall psychotic symptoms (SMD = –1.13, 95% CI = –1.98 to –0.27) and positive symptoms (SMD = –0.72, 95% CI =–1.31 to –0.12), while the effect on negative symptoms did not reach statistical significance (SMD = –0.93, 95% CI = –1.90 to 0.04). A significant positive effect was also observed on attention/processing speed (SMD = 0.37, 95% CI = 0.12 to 0.61). CONCLUSIONS: These findings support the idea that some compounds that stimulate 5-HT(1A) receptors provide an effective pharmacologic enhancer in the treatment of schizophrenia. Further clinical trials are warranted to determine the benefits of the adjunctive use of 5-HT(1A) partial agonists in ameliorating symptoms and improving functional outcomes in patients with schizophrenia or other psychiatric disorders.