2017 Update Project #2: Acute Pediatric Major Depressive Disorder

Principal Investigator: Dr. Kristen Hollinger, Johns Hopkins University

Research Description: This pre-clinical project repurposes a drug for high blood pressure (pindolol) and a drug for anxiety (buspirone) to reduce the negative impulsivity and suicidal effects of SSRIs used to treat depression. Previous research suggests that a rapid drop in serotonin release during acute exposure to antidepressant treatment could account for this increase in suicidal behaviors. Pindolol and buspirone block a specific receptor in the brain, thereby allowing more serotonin to be released during acute antidepressant treatment. Dr. Hollinger will study the effects of dose and age of treatment of the repurposed drugs in mice, alone and in combination with the SSRI fluoxetine. This trial will lay the groundwork for future clinical trials in an area of unmet need. In addition, another researcher on the team is conducting a separate study to validate a genetic test to identify those children and young adults at greater risk when treated with SSRIs for depression.

Project Length: 12 months

Current Updates: Dr. Hollinger’s funding began in late November 2016. To date, she has:

  • Determined the most effective dose of pindolol for use alone and in combination with fluoxetine
  • Begun testing multiple doses of buspirone to the most effective dose for use alone and in combination with fluoxetine
  • Future work will examine drug effects at varying mouse ages in order to determine if the combination therapy has differing efficacy at certain life stages (e.g. childhood, adolescence, young adulthood)

This combination treatment of pindolol or buspirone with an SSRI has the potential to positively impact the millions of children and young adults who experience depression every year.