Rapid Antidepressant Action of Common Medication Confirmed by Repeat Trial

May 4, 2010 • Science Update

Confirming results from earlier research, a clinical trial of treatment for major depression showed that the medication scopolamine, commonly used for motion sickness and as a sedative, could lift symptoms of depression within days, far faster than current antidepressants. Though the study was small, the magnitude of scopolamine's effects in comparison with placebo suggests that this class of medications has potential for rapid treatment of depression.

Background

Currently available antidepressants typically require 3 to 4 weeks to take effect. In addition, despite a range of existing medications for depression, it's estimated that 30 to 40 percent of patients do not respond at all to antidepressants. Developing new medications that act with alternative mechanisms to those already available—and more quickly—is an important goal of current research.

The most commonly used antidepressant medications affect signaling by serotonin, a neurotransmitter known to play a role in mood. Scopolamine interacts with cell receptors for another neurotransmitter, acetylcholine. Scopolamine is one of a class of compounds that block a specific type of receptor for acetylcholine (muscarinic receptors). Although various lines of research have suggested that acetylcholine-related activity plays a role in depression, to date, other neurotransmitter systems have been thought to be more central in the development of depression.

This Study

This study sought to replicate an earlier trial that demonstrated the ability of scopolamine to relieve symptoms of depression quickly in a group of patients with major depressive disorder or bipolar disorder. The current study focused on people with major depressive disorder. Like the earlier study, this one compared scopolamine with placebo, and was double-blind in that neither patients nor clinicians administering medication knew whether patients were receiving placebo or scopolamine (both were given intravenously).

After an initial treatment session in which all 22 patients in the trial received placebo once, half then received scopolamine three times, each treatment 3 to 5 days apart, and then placebo three more times, 3 to 5 days apart. The other half, after the initial placebo dose, received placebo three more times, then scopolamine three times. Patients receiving scopolamine first reported positive effects by the time they returned for a second dose 3 to 5 days later; many even reported improvement by the morning following treatment. After three treatments, their scores on a test for depression symptoms declined by 32 percent compared with 6.5 percent for placebo. These improved scores persisted until the end of the trial. Those receiving scopolamine after placebo had a 53 percent reduction in depression scores by the end of the clinical trial. Eleven of those in the trial experienced complete remission (one of those while on placebo).

Side-effects of scopolamine included drowsiness, dry mouth, light headedness, and blurred vision, but they were transient, resolving within hours.

Significance

Depression is a costly disease for both society and individuals. It is a leading cause of disability worldwide. For individuals and their family members, major depression is painful and frightening; depression is the predominant risk factor for suicide, the 11th leading cause of death in the U.S. The need for effective, rapid treatment alternatives is an urgent one.

While this is a small study, the difference between the response to scopolamine and placebo was statistically significant. By the end of the study 14 of the 22, or 64 percent of subjects, had achieved at least a 50 percent reduction in symptoms.

Subjects in the study reported short-term sedation but not euphoria with scopolamine. The antidepressant effects persisted weeks after the medication was no longer in the bloodstream. It is possible, according to the authors, that scopolamine's antidepressant effects escaped notice earlier because it is usually used in smaller doses (such as for motion sickness) than in this study. The authors note the importance of replicating this work in larger groups of patients and developing more practical means of administering scopolamine. Further research will also provide information on the exact mechanism of action of the drug, a guide to development of additional new medications.

References

Drevets, W.C. and Furey, M.L. Replication of scopolamine's antidepressant efficacy in major depressive disorder: a randomized, placebo-controlled clinical trial. Biological Psychiatry 67:432-8, 2010.

Furey, M.L. and Drevets, W.C. Antidepressant efficacy of the antimuscarinic drug scopolamine. Archives of General Psychiatry 63:1121-1129, 2006.