The effects of intramuscular administration of scopolamine augmentation in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled trial

Introduction: Major depressive disorder (MDD) is a common affective disorder. Currently established pharmacotherapies lack rapid clinical response, thereby limiting their ability to bring instant relief to patients. A series of clinical trials has demonstrated the antidepressant effects of scopolamine, yet few have studied the effects of add-on scopolamine to currently available antidepressants. It is not known whether conventional antidepressant treatment with a 3-day scopolamine injection could speed up oral antidepressant efficacy. The main focus of this study is to detect the capacity of the rapid-onset efficacy of such a treatment option.

Methods and analysis: This study consisted of a single-centre, double-blind, three-arm randomized trial with a 4-week follow-up period. Sixty-six participants meeting entry criteria were randomly allocated to three treatment groups: a high-dose group, a low-dose group and a placebo control group. Psychiatric rating scales were administered at baseline and seven viewing points following the administration of intramuscular injections. The primary outcome measure was length of time from randomization (baseline) to early improvement.

Results: Both primary and secondary outcome measures consistently showed no differences among the three groups. The cumulative response rate and the remission rate were 72.7% (48/66) and 47.0% (31/66). Intramuscular scopolamine treatment was relatively well tolerated. Two subjects with high-dose injections dropped out because of a drug-related side effect.

Conclusion: Contrary to our prediction, we found that, compared to placebo (0.9% saline i.m.), scopolamine was not associated with a significantly faster antidepressant response rate.

Trial registration: ClinicalTrials.gov, NCT03131050. Registered on 18 April 2017.

Keywords: add-on; efficacy; intramuscular; major depressive disorder; scopolamine.