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Meta-Analysis
. 2023 Apr 17;26(4):249-258.
doi: 10.1093/ijnp/pyad004.

Effect of 5-HT1A Receptor Partial Agonists of the Azapirone Class as an Add-On Therapy on Psychopathology and Cognition in Schizophrenia: A Systematic Review and Meta-Analysis

Risa Yamada  1   2 , Ayumu Wada  1   2   3 , Andrew Stickley  1 , Yuma Yokoi  4 , Tomiki Sumiyoshi  1   2   3
Affiliations
Meta-Analysis

Effect of 5-HT1A Receptor Partial Agonists of the Azapirone Class as an Add-On Therapy on Psychopathology and Cognition in Schizophrenia: A Systematic Review and Meta-Analysis

Risa Yamada et al. Int J Neuropsychopharmacol. .

Abstract

Background: There are ongoing efforts to examine the effect of 5-HT1A 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-HT1A 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-HT1A partial agonists in ameliorating symptoms and improving functional outcomes in patients with schizophrenia or other psychiatric disorders.

Keywords: 5-HT1A receptor partial agonist; atypical antipsychotic drugs; cognitive dysfunction; psychopathology; schizophrenia.

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Figures

Figure 1.
Figure 1.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) study selection flowchart.
Figure 2.
Figure 2.
Risk of bias.
Figure 3.
Figure 3.
Funnel plot for overall psychopathology.
Figure 4.
Figure 4.
Mean effect of 5-hydroxtrypatamine (5-HT)1A receptor partial agonists of the azapirone class as an add-on therapy on overall psychopathology (A), Positive symptoms (B), Negative symptoms (C), and Attention/processing speed (D).
See this image and copyright information in PMC

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