Kristen HollingerInvestigator: Dr. Kristen Hollinger

Disease: Pediatric Depression

Research Description: Suicide due to major depressive disorder (MDD) has simultaneously become a leading cause of death around the world (particularly among children, adolescents and young adults) and a growing silent epidemic for which we have made little to no progress for decades. The current standard of care for severe MDD includes antidepressant drug treatment, such as a selective serotonin reuptake inhibitor (SSRI), often in combination with cognitive behavioral therapy. It takes approximately 4 weeks for SSRIs to produce mood-lifting effects, and during that time, particularly in pediatric populations, an increase in suicidal behaviors can be seen. Our research suggests that a rapid drop in serotonin release during acute exposure to antidepressant treatment could account for this increase in suicidal behaviors. To overcome the initial drop in serotonin, we propose the use of repurposed drugs, pindolol and buspirone, to be delivered in combination with a SSRI antidepressant for the first month of treatment. Pindolol and buspirone block a specific serotonergic receptor in the brain, thereby allowing more serotonin to be released during acute antidepressant treatment. This combination has the potential to prevent suicidal behaviors following SSRI treatment. Preclinical studies in mice will evaluate the efficacy and appropriate doses of pindolol or buspirone to be translated to human studies.

CWR funding role: Primary funder

CWR funding start date: December 2016

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