Replication of Scopolamine's Antidepressant Efficacy in Major Depressive Disorder: A Randomized, Placebo-Controlled Clinical Trial

doi:10.1016/j.biopsych.2009.11.021

Biological Psychiatry

Volume 67, Issue 5, 1 March 2010, Pages 432-438

https://doi.org/10.1016/j.biopsych.2009.11.021 Get rights and content

Background

We previously reported that intravenous (IV) scopolamine administration produced rapid and robust antidepressant effects in a sample consisting of both unipolar and bipolar depressives. The present study aimed to replicate this finding in an independent sample limited to unipolar depressives.

Methods

Outpatients with major depressive disorder (MDD; n = 23; 22 were included in analyses) participated in a double-blind, placebo-controlled, crossover trial. Subjects were randomized into either a P/S or S/P sequence (P = block of three placebo sessions; S = block of three scopolamine sessions; [4.0 μg/kg IV]). Sessions occurred 3 to 5 days apart, such that time spent in each block lasted 1.5 to 2 weeks and the interval between blocks was 3 to 5 days. The Montgomery-Asberg Depression Rating Scale (MADRS) served as the primary outcome measure.

Results

Following the initial block, the group receiving scopolamine first (S/P) showed a 32% reduction in MADRS scores (p < .001), which exceeded the corresponding change of 6.5% under placebo (P/S; p = .009), confirming the a-priori hypothesis. Improvement was significant at the first evaluation that followed scopolamine administration (p = .011). In Block 2, the P/S group showed a 53% reduction in MADRS scores (p = .001) following scopolamine versus placebo, whereas the reduction seen in S/P subjects who received scopolamine during Block 1 persisted as they received placebo during Block 2. Scopolamine induced drowsiness, blurred vision, dry mouth, light-headedness, and reduced blood pressure, which were sufficiently well tolerated that no subject dropped out because of side effects.

Conclusions

These results replicate previous finding that scopolamine produces a rapid and robust antidepressant response.

Section snippets

Participants

Volunteers between 18 and 45 years of age evaluated at the NIMH outpatient clinic were assessed for eligibility if they were nonsmokers and met DSM-IV (3) criteria for recurrent MDD on the basis of an unstructured interview conducted by a psychiatrist and the Structured Clinical Interview for DSM-IV. Exclusion criteria included exposure to psychotropic drugs or other medications likely to affect cholinergic function within 3 weeks (8 weeks for fluoxetine), serious risk of suicide, delusions or

Subjects

The passage of subjects through the phases of this clinical trial is detailed in Figure S1 in Supplement 1. Of 42 eligible patients, 19 were assessed for eligibility but were excluded for not meeting entrance criteria (n = 6) or declining to participate (n = 13), so 23 were randomized into the study. One subject dropped out after randomization but before Session 1, so this subject did not contribute any data to the analysis. Twenty-one subjects completed the trial as intended, and another

Discussion

Scopolamine (4.0 μg/kg IV) showed antidepressant efficacy relative to placebo in unipolar depressive patients, replicating the results we obtained previously in an independent sample of depressed patients that included both unipolar and bipolar patients (2). Our study used a crossover design, so the improvement observed independently in the two treatment groups provided additional, within-study replications of the antidepressant effect. Between the baseline block and experimental Block 1, the

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Archival ReportReplication of Scopolamine's Antidepressant Efficacy in Major Depressive Disorder: A Randomized, Placebo-Controlled Clinical Trial

Background

Methods

Results

Conclusions

Section snippets

Participants

Subjects

Discussion

Eur J Pharmacol

Biol Psychiatry

Biol Psychiatry

Lancet

J Psychiatr Res

J Chem Neuroanat

Biol Psychiatry

Biochem Biophys Res Commun

Neuropsychopharmacology

J Affect Disord

J Psychiatr Res

J Affect Disord

Trends in the development of new antidepressantsIs there a light at the end of the tunnel?

Curr Med Chem

Antidepressant efficacy of the antimuscarinic drug scopolamine: A randomized, placebo-controlled clinical trial

Arch Gen Psychiatry

Diagnostic and Statistical Manual of Mental Disorders

Relative sensitivity of the Montgomery-Asberg depression rating scale, the Hamilton depression rating scale and the clinical global impressions rating scale in antidepressant clinical trials

Int Clin Psychopharmacol

The assessment of anxiety states by rating

Br J Med Psychol

A rating scale for mania: Reliability, validity and sensitivity

Br J Psychiatry

EITS Manual for the Profile of Mood States

Definitions of antidepressant treatment response, remission, nonresponse, partial response, and other relevant outcomes: A focus on treatment-resistant depression

J Clin Psychiatry

Archival Report
Replication of Scopolamine's Antidepressant Efficacy in Major Depressive Disorder: A Randomized, Placebo-Controlled Clinical Trial