The Antidepressant Efficacy of the Anticholinergic Scopolamine

Phase 2

Terminated

Conditions: Unipolar Depression
Bipolar Depression

Interventions: Drug: Scopolamine

Registration Number: NCT00369915

Lead Sponsor: National Institute of Mental Health (NIMH)

Brief Summary: A previous study showed that the intravenous administration of scopolamine produces antidepressant effects. This study is designed to determine if other routes of administration of scopolamine produce antidepressant effects.

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 17

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Plac/Scop	Scopolamine	Placebo then scopolamine
Scop/Plac	Scopolamine	Scopolamine then placebo

Primary Outcome Measures

Name	Time	Method
Change in Depression Severity	Outcome measures obtained at each of 12 sessions	The Montgomery-Asberg Depression Rating Scale (MADRS) has a range of scores from 0 to 60 where the highest values indicate the most depression.

Secondary Outcome Measures

Name	Time	Method
Hamilton Anxiety Rating Scale	Each of 12 sessions.	The Hamilton Anxiety Rating Scale (HARS) has a range of scores from 0 to 56 where the highest values indicate the most anxiety.