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Augmentation Therapy With Serotonin 5-HT1A Receptor Partial Agonists on Cognitive Function in Depressive Disorders: A
Risa Yamada1,2, Ayumu Wada1,2, Andrew Stickley1
1Department of Preventive Intervention for Psychiatric Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
Neuropsychopharmacology Reports
|May 27, 2025
Summary
Adjunctive serotonin 5-HT1A receptor partial agonists (5-HT1A-PAs) show promise in improving cognitive deficits in major depressive disorder and vascular depression. Further research is needed to explore novel agonists for enhanced cognitive benefits.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Serotonin 5-HT1A receptor partial agonists (5-HT1A-PAs) are explored for their role in mood disorders and cognitive function.
- Evidence suggests 5-HT1A receptor stimulation may accelerate antidepressant effects.
- This review investigates the efficacy of adjunctive 5-HT1A-PAs in improving cognitive function in patients with depressive symptoms.
Approach:
- Systematic review of randomized controlled trials (RCTs) published between 1987 and January 2024.
- Searched PubMed, Cochrane Library, and Web of Science databases.
- Included human studies on psychiatric disorders (excluding schizophrenia) evaluating cognitive functions.
Key Points:
- Three RCTs met the inclusion criteria, focusing on vascular depression and major depressive disorder (MDD).
- In MDD, combined buspirone and melatonin improved subjective cognitive disturbances more than buspirone alone or placebo.
- In vascular depression, escitalopram-tandospirone combination improved executive function and verbal fluency compared to escitalopram alone.
Conclusions:
- Adjunctive 5-HT1A-PAs demonstrate potential in ameliorating cognitive deficits in specific depressive disorders.
- Further investigation into novel 5-HT1A receptor agonists is warranted for potentially greater cognitive benefits.
- These findings highlight the therapeutic potential of targeting the 5-HT1A pathway for cognitive enhancement in mood disorders.
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