The Antidepressant Efficacy of the Anticholinergic Scopolamine
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||The Antidepressant Efficacy of the Anticholinergic Scopolamine|
- Change in Depression Severity [ Time Frame: Outcome measures obtained at each of 12 sessions ] [ Designated as safety issue: No ]The Montgomery-Asberg Depression Rating Scale (MADRS) has a range of scores from 0 to 60 where the highest values indicate the most depression.
- Hamilton Anxiety Rating Scale [ Time Frame: Each of 12 sessions. ] [ Designated as safety issue: No ]The Hamilton Anxiety Rating Scale (HARS) has a range of scores from 0 to 56 where the highest values indicate the most anxiety.
|Study Start Date:||August 2006|
|Study Completion Date:||January 2013|
|Primary Completion Date:||January 2013 (Final data collection date for primary outcome measure)|
Placebo then scopolamine
Scopolamine then placebo
Despite the availability of a wide range of antidepressant drugs, clinical trials indicate that 30% to 40% of patients with major depression fail to respond to first-line antidepressant treatment, despite adequate dosage, duration, and compliance. Moreover, in those patients who do experience symptomatic relief following conventional anti-depressant treatment, clinical improvement is not evident for 3-4 weeks. Thus, there is a clear need to develop novel and improved therapeutics for unipolar and bipolar depression.
The cholinergic system is one of the neurotransmitter systems implicated in the pathophysiology of mood disorders. Evidence suggests that during major depressive episodes, the cholinergic system is hypersensitive to acetylcholine. Agents that enhance muscarinic cholinergic receptor function increase depressive symptoms in depressed subjects, and can produce symptoms of depression in healthy individuals. The preclinical literature more specifically implicates the muscarinic receptors and indicates that the use of muscarinic antagonists, in the context of animal models of depression, results in improvement in the behavioral analogs of depression.
Preliminary results obtained under protocol 3-M-0108 provide strong evidence for the potential effectiveness of the anticholinergic scopolamine in rapidly producing clinically significant antidepressant effects. We observed large reductions in Montgomery-Asberg Depression Rating Scale (MADRS) scores that occurred over hours/days following i.v. infusion of scopolamine, which stood in marked contrast to the 3-4 week period generally required for conventional therapies. Moreover, these improvements were observed in subjects who had been nonresponsive or incompletely responsive to conventional antidepressant therapies, highlighting the potential for this treatment to benefit a larger percentage of individuals with depression. The goal of this research project is to perform a clinical trial to evaluate the efficacy of the muscarinic cholinergic receptor antagonist scopolamine administered via transdermal patch on clinical symptoms of depression.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00369915
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Maura L Furey, Ph.D.||National Institute of Mental Health (NIMH)|