Augmentation therapy with serotonin1A receptor partial agonists on neurocognitive function in schizophrenia: A systematic review and meta-analysis

Risa Yamada; Ayumu Wada; Andrew Stickley; Yuma Yokoi; Tomiki Sumiyoshi

doi:10.1016/j.scog.2023.100290

Augmentation therapy with serotonin_1A receptor partial agonists on neurocognitive function in schizophrenia: A systematic review and meta-analysis

Schizophr Res Cogn. 2023 Sep 14:34:100290. doi: 10.1016/j.scog.2023.100290. eCollection 2023 Dec.

Authors

Risa Yamada^{1

2

3}, Ayumu Wada^{1

2

4}, Andrew Stickley¹, Yuma Yokoi⁵, Tomiki Sumiyoshi^{1

2

4}

Affiliations

¹ Department of Preventive Intervention for Psychiatric Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo 187-8553, Japan.
² Department of Psychiatry, National Center Hospital of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo 187-8551, Japan.
³ Department of Psychiatry, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan.
⁴ Department of Brain Bioregulatory Science, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo 105-8461, Japan.
⁵ Department of Educational Promotion, Clinical Research and Education Promotion Division, National Center of Neurology and Psychiatry, National Center Hospital, 4-1-1, Ogawahigashi, Kodaira, Tokyo 187-8551, Japan.

Abstract

Background: In a previous meta-analysis, the use of serotonin_1A(5-HT_1A) receptor partial agonists of the azapirone class as an add-on therapy was associated with beneficial effects on positive symptoms and attention/processing speed in schizophrenia patients. This meta-analysis builds on that study by examining the effects of adjunctive treatment with 5-HT_1A partial agonists in improving other domains of neurocognitive function in schizophrenia patients.

Methods: A literature search was performed from 1987 to May 2023 to identify randomized controlled trials. The standardized mean difference (SMD) with 95 % confidence intervals (CI) was calculated when there were two or more studies. Four studies, involving 313 patients, met the inclusion criteria and were used in the analysis.

Results: 5-HT_1A partial agonists (buspirone or tandospirone) did not have a significant effect on verbal learning (SMD = 0.08, 95 % CI = -0.31 to 0.47) or working memory (SMD = 0.15, 95 % CI = -0.09 to 0.39). Regarding executive functions (Wisconsin Card Sorting Test), positive but non-significant results were seen with the category number (SMD = 0.26, 95 % CI = -0.81 to 1.32), while non-significant effects were noted for percent preservation errors (SMD = -0.10, 95 % CI = -0.53 to 0.33).

Conclusions: The absence of any significant benefits in the cognitive domains studied here may have been due to the variance in the concomitant medication (typical vs atypical antipsychotic drugs), the level of cognition at baseline, or other factors. Further studies with various types of 5-HT_1A agonists are warranted to examine the potential cognitive efficacy of stimulating these receptors.

Keywords: 5-HT1A receptor partial agonist; Atypical antipsychotic drugs; Azapirone derivative; Cognitive dysfunction; Schizophrenia.