An exploratory study of combination buspirone and melatonin SR in major depressive disorder (MDD): a possible role for neurogenesis in drug discovery.
Study Goal
The researchers aimed to determine whether a combination of buspirone and melatonin could serve as an effective antidepressant treatment, using both preclinical and clinical assessments.
Results Summary
The combination of buspirone and melatonin showed significant antidepressant effects in subjects with Major Depressive Disorder (MDD), outperforming placebo and buspirone monotherapy on multiple clinical measures. Neither buspirone nor melatonin alone demonstrated antidepressant activity in preclinical assays.
Population
Subjects with acute Major Depressive Disorder (MDD)
Effective Dosage
Melatonin-SR 3 mg combined with buspirone 15 mg
Duration
6 weeks
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
buspirone and melatonin | increase | antidepressant activity | in vitro neurogenesis-based human neural stem cell (hNSCs) assays and rodent in vivo behavioral assays | - | displayed antidepressant activity | #1 |
buspirone | no change | antidepressant-like profile | in vitro neurogenesis-based human neural stem cell (hNSCs) assays and rodent in vivo behavioral assays | - | showed no antidepressant-like profile | #2 |
melatonin | no change | antidepressant-like profile | in vitro neurogenesis-based human neural stem cell (hNSCs) assays and rodent in vivo behavioral assays | - | showed no antidepressant-like profile | #3 |
low dose buspirone 15 mg combined with melatonin-SR 3 mg | increase | antidepressant efficacy | pre-clinical platform | - | yielded optimal antidepressant efficacy | #4 |
low dose of buspirone | decrease | adverse event liability | - | minimal | suggested that antidepressant efficacy might be achieved with only minimal adverse event liability | #5 |
combination of buspirone and melatonin | increase | antidepressant response | subjects with acute Major Depressive Disorder (MDD) | - | revealed a significant antidepressant response | #6 |
combination of buspirone and melatonin | increase | Clinical Global Impression of Severity and Improvement | subjects with acute Major Depressive Disorder (MDD) | - | revealed a significant antidepressant response | #7 |
combination of buspirone and melatonin | increase | Inventory of Depressive Symptomatology | subjects with acute Major Depressive Disorder (MDD) | - | revealed a significant antidepressant response | #8 |
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.