An exploratory study of combination buspirone and melatonin SR in Major Depressive Disorder (MDD): A possible role for neurogenesis in drug discovery
Abstract
We used in vitro neurogenesis-based human neural stem cell (hNSCs) assays and rodent in vivo behavioral assays to identify potential novel antidepressants. A combination of buspirone and melatonin displayed antidepressant activity in these assays whereas neither buspirone nor melatonin alone showed any antidepressant-like profile. After evaluating numerous combination ratios, we determined that low dose buspirone 15 mg combined with melatonin-SR 3 mg yielded optimal antidepressant efficacy in our pre-clinical platform. The low dose of buspirone suggested that antidepressant efficacy might be achieved with only minimal adverse event liability. Based on these data, we conducted an exploratory 6-week, multi-center, double-blind, randomized, placebo- and comparator-controlled study of the combination of buspirone and melatonin in subjects with acute Major Depressive Disorder (MDD). The combination treatment revealed a significant antidepressant response in subjects with MDD on several measures (Clinical Global Impression of Severity and Improvement, Inventory of Depressive Symptomatology) compared to either placebo or buspirone 15 mg monotherapy. These preliminary findings have clinical implications and suggest that a platform of pre-clinical neurogenesis matched with confirmatory behavioral assays may be useful as a drug discovery strategy.
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In a 6-week double-blind RCT, the combination of melatonin and buspirone provided beneficial effects in treating depressive severity in individuals with major depressive disorder.
“In a 6-week double-blind RCT, the combination of melatonin and buspirone provided beneficial effects in treating depressive severity in individuals with MDD [143].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [143]
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- Authors
- Fava, M., Targum, S. D., Nierenberg, A. A., Bleicher, L. S., Carter, T. A., Wedel, P. C., Hen, R., Gage, F. H., & Barlow, C.
- Affiliations
- Massachusetts General Hospital (US)
- Columbia University (US)
- Salk Institute for Biological Studies (US)
- Corresponding author
- Targum, Steven D.
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 46
- Issue
- 12
- Pages
- 1553-1563
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2131584217
- Cited by
- 67
- References
- 76
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 1 · 2017: 7 · 2016: 5 · 2015: 9 · 2014: 7 · 2013: 5
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- buspirone, melatonin, major depressive disorder, antidepressant drug discovery, combination therapy, human neural stem cells, antidepressant efficacy, acute depression
- MeSH terms
- Adult, Animals, Behavior, Animal, Buspirone, Delayed-Action Preparations, Major Depressive Disorder, Double-Blind Method, Drug Synergism, Drug Therapy, Combination, Female, Humans, Male, Melatonin, Middle Aged, Placebos, Rats, Inbred F344, Treatment Outcome, Rats, Neurogenesis
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