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

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-HT1A 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 25 February 2022 to identify randomized controlled trials. The standardized mean difference (SMD) with 95% confidence intervals (CI) was calculated when there were two 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 might 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.

Pharmacological management of neurocognitive impairment in schizophrenia: A narrative review

“…Our search identified one positive study on Buspirone by Wang et al 46 It includes 196 patients and demonstrated that co‐treatment of buspirone with atypical antipsychotics outperformed atypical antipsychotics alone in improvements in logical reasoning, generalization, visual discrimination/memory/comprehension, and spatial coordination in patients with schizophrenia, supporting the notion that cognitive dysfunction in schizophrenia may be alleviated through 5‐HT1A stimulation. A recent meta‐analysis in this area suggested that buspirone can improve attention and processing speed in patients with schizophrenia 47 …”

“…A recent meta‐analysis in this area suggested that buspirone can improve attention and processing speed in patients with schizophrenia. 47 …”

Side effects and cognitive benefits of buspirone: A systematic review and meta-analysis

“…Our results are consistent with previous research findings. A recent meta-analysis showed that buspirone can help improve attention in patients with schizophrenia [ 50 ]. As a 5-HT1A receptor agonist, the potential mechanism of the cognitive benefits of buspirone may be related to the activation of 5-HT1A receptors.…”

Assessing NH300094, a novel dopamine and serotonin receptor modulator with cognitive enhancement property for treating schizophrenia

“…The stimulation of the 5-HT 1A receptor often interferes with memory-encoding mechanisms in brain, which leading to learning disabilities. However, antagonists of 5-HT 1A receptor can enhance cortical cholinergic/hippocampal and/or glutamatergic neurotransmission, which promoting certain types of memory ( Ogren et al, 2008 ; Yamada et al, 2023 ). 5-HT 1A antagonists reversed the cognitive impairment induced by NMDA receptor antagonists or mACh receptor antagonists ( Luttgen et al, 2005 ; Madjid et al, 2006 ).…”