Augmentation Therapy With Serotonin 5‐HT1A Receptor Partial Agonists on Cognitive Function in Depressive Disorders: A Systematic Review of Randomized Controlled Studies

ABSTRACT Objective The use of serotonin 5‐HT1A receptor partial agonists (5‐HT1A‐PAs) as an add‐on therapy has been associated with the enhancement of attention/processing speed in patients with schizophrenia. Also, 5‐HT1A receptors have been shown to play a role in the pathophysiology of mood disor...

Full description

Saved in:
Bibliographic Details
Main Authors: Risa Yamada, Ayumu Wada, Andrew Stickley, Adrian Newman‐Tancredi, Tomiki Sumiyoshi
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Neuropsychopharmacology Reports
Subjects:
Online Access:https://doi.org/10.1002/npr2.70023
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849683322236567552
author Risa Yamada
Ayumu Wada
Andrew Stickley
Adrian Newman‐Tancredi
Tomiki Sumiyoshi
author_facet Risa Yamada
Ayumu Wada
Andrew Stickley
Adrian Newman‐Tancredi
Tomiki Sumiyoshi
author_sort Risa Yamada
collection DOAJ
description ABSTRACT Objective The use of serotonin 5‐HT1A receptor partial agonists (5‐HT1A‐PAs) as an add‐on therapy has been associated with the enhancement of attention/processing speed in patients with schizophrenia. Also, 5‐HT1A receptors have been shown to play a role in the pathophysiology of mood disorders. There is compelling evidence supporting that stimulation of 5‐HT1A receptors accelerates antidepressant effects. Accordingly, this systematic review examines the ability of adjunctive treatment with 5‐HT1A‐PAs to improve cognitive function in patients with depressive symptoms. Methods A literature search using PubMed, the Cochrane Library, and Web of Science databases was performed from 1987 to January 2024 to identify randomized controlled trials (RCTs) corresponding to the following inclusion criteria: (1) RCTs, (2) human studies; studies that (3) targeted patients with a psychiatric disorder (except for schizophrenia or schizoaffective disorder), (4) evaluated the effect of cognitive functions, (5) were written in English. Results From the 80 studies initially screened, three met the inclusion criteria. Two of these studies dealt with vascular depression while one focused on major depressive disorder (MDD). In MDD, combined treatment with buspirone and melatonin was more efficacious in ameliorating subjective cognitive disturbances compared to the use of buspirone alone or the use of a placebo. Likewise, the combination of escitalopram–tandospirone was more advantageous than escitalopram alone for improving executive function and verbal fluency in patients with vascular depression. Conclusions Further studies with novel 5‐HT1A receptor agonists are warranted to examine their potentially more robust benefits on cognitive performance in subjects suffering from mood deficits.
format Article
id doaj-art-df33e8a231d946fbae17a3a61f73e940
institution DOAJ
issn 2574-173X
language English
publishDate 2025-06-01
publisher Wiley
record_format Article
series Neuropsychopharmacology Reports
spelling doaj-art-df33e8a231d946fbae17a3a61f73e9402025-08-20T03:23:56ZengWileyNeuropsychopharmacology Reports2574-173X2025-06-01452n/an/a10.1002/npr2.70023Augmentation Therapy With Serotonin 5‐HT1A Receptor Partial Agonists on Cognitive Function in Depressive Disorders: A Systematic Review of Randomized Controlled StudiesRisa Yamada0Ayumu Wada1Andrew Stickley2Adrian Newman‐Tancredi3Tomiki Sumiyoshi4Department of Preventive Intervention for Psychiatric Disorders National Institute of Mental Health, National Center of Neurology and Psychiatry Tokyo JapanDepartment of Preventive Intervention for Psychiatric Disorders National Institute of Mental Health, National Center of Neurology and Psychiatry Tokyo JapanDepartment of Preventive Intervention for Psychiatric Disorders National Institute of Mental Health, National Center of Neurology and Psychiatry Tokyo JapanNeurolixis Castres FranceDepartment of Preventive Intervention for Psychiatric Disorders National Institute of Mental Health, National Center of Neurology and Psychiatry Tokyo JapanABSTRACT Objective The use of serotonin 5‐HT1A receptor partial agonists (5‐HT1A‐PAs) as an add‐on therapy has been associated with the enhancement of attention/processing speed in patients with schizophrenia. Also, 5‐HT1A receptors have been shown to play a role in the pathophysiology of mood disorders. There is compelling evidence supporting that stimulation of 5‐HT1A receptors accelerates antidepressant effects. Accordingly, this systematic review examines the ability of adjunctive treatment with 5‐HT1A‐PAs to improve cognitive function in patients with depressive symptoms. Methods A literature search using PubMed, the Cochrane Library, and Web of Science databases was performed from 1987 to January 2024 to identify randomized controlled trials (RCTs) corresponding to the following inclusion criteria: (1) RCTs, (2) human studies; studies that (3) targeted patients with a psychiatric disorder (except for schizophrenia or schizoaffective disorder), (4) evaluated the effect of cognitive functions, (5) were written in English. Results From the 80 studies initially screened, three met the inclusion criteria. Two of these studies dealt with vascular depression while one focused on major depressive disorder (MDD). In MDD, combined treatment with buspirone and melatonin was more efficacious in ameliorating subjective cognitive disturbances compared to the use of buspirone alone or the use of a placebo. Likewise, the combination of escitalopram–tandospirone was more advantageous than escitalopram alone for improving executive function and verbal fluency in patients with vascular depression. Conclusions Further studies with novel 5‐HT1A receptor agonists are warranted to examine their potentially more robust benefits on cognitive performance in subjects suffering from mood deficits.https://doi.org/10.1002/npr2.700235‐HT1A receptor biased agonists5‐HT1A receptor partial agonistsazapirone derivativecognitive impairmentdepression
spellingShingle Risa Yamada
Ayumu Wada
Andrew Stickley
Adrian Newman‐Tancredi
Tomiki Sumiyoshi
Augmentation Therapy With Serotonin 5‐HT1A Receptor Partial Agonists on Cognitive Function in Depressive Disorders: A Systematic Review of Randomized Controlled Studies
Neuropsychopharmacology Reports
5‐HT1A receptor biased agonists
5‐HT1A receptor partial agonists
azapirone derivative
cognitive impairment
depression
title Augmentation Therapy With Serotonin 5‐HT1A Receptor Partial Agonists on Cognitive Function in Depressive Disorders: A Systematic Review of Randomized Controlled Studies
title_full Augmentation Therapy With Serotonin 5‐HT1A Receptor Partial Agonists on Cognitive Function in Depressive Disorders: A Systematic Review of Randomized Controlled Studies
title_fullStr Augmentation Therapy With Serotonin 5‐HT1A Receptor Partial Agonists on Cognitive Function in Depressive Disorders: A Systematic Review of Randomized Controlled Studies
title_full_unstemmed Augmentation Therapy With Serotonin 5‐HT1A Receptor Partial Agonists on Cognitive Function in Depressive Disorders: A Systematic Review of Randomized Controlled Studies
title_short Augmentation Therapy With Serotonin 5‐HT1A Receptor Partial Agonists on Cognitive Function in Depressive Disorders: A Systematic Review of Randomized Controlled Studies
title_sort augmentation therapy with serotonin 5 ht1a receptor partial agonists on cognitive function in depressive disorders a systematic review of randomized controlled studies
topic 5‐HT1A receptor biased agonists
5‐HT1A receptor partial agonists
azapirone derivative
cognitive impairment
depression
url https://doi.org/10.1002/npr2.70023
work_keys_str_mv AT risayamada augmentationtherapywithserotonin5ht1areceptorpartialagonistsoncognitivefunctionindepressivedisordersasystematicreviewofrandomizedcontrolledstudies
AT ayumuwada augmentationtherapywithserotonin5ht1areceptorpartialagonistsoncognitivefunctionindepressivedisordersasystematicreviewofrandomizedcontrolledstudies
AT andrewstickley augmentationtherapywithserotonin5ht1areceptorpartialagonistsoncognitivefunctionindepressivedisordersasystematicreviewofrandomizedcontrolledstudies
AT adriannewmantancredi augmentationtherapywithserotonin5ht1areceptorpartialagonistsoncognitivefunctionindepressivedisordersasystematicreviewofrandomizedcontrolledstudies
AT tomikisumiyoshi augmentationtherapywithserotonin5ht1areceptorpartialagonistsoncognitivefunctionindepressivedisordersasystematicreviewofrandomizedcontrolledstudies