Naltrexone and Scopolamine Rapidly Reduce Symptoms of Major Depressive Disorder (MDD): A Double Blinded Randomized Controlled Pilot Study

Background: Scopolamine and naltrexone are FDA approved medications that have been utilized off label for the indication of major depressive disorder (MDD). We examined the efficacy of the 2 medications in combination for major depression. Methods: 14 adults (7 female and 7 males) with current major depressive disorder were randomized by coin flip to 0.15 mg BID of scopolamine and 1 mg BID naltrexone or placebo for a total of 4 weeks. Modified MDRS questionnaires were utilized to monitor progress in depression symptomatology. The placebo patients were crossed over to the active medications subsequent to the 4 week trial period. Results: 2 subjects dropped out of the trial as a result of side effects. A total of 12 subjects completed the trial. The average reduction in Modified MDRS scores over the 4 weeks for the active medications was 12.5. The average reduction noted in control patients was 3.5. This difference was statistically significant with P = 0.03, less than 0.05 for a greater than 95% confidence interval utilizing Student’s T test analysis. Of the 4 patients that crossed over to the active medications three additional patients noted a partial or complete response to the medications with an average reduction and Modified MDRS scores of 8. No washout periods were utilized before the trial or for the crossover period. Conclusion: The combination of scopolamine and naltrexone demonstrated significant benefit for MDD.