Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized,
placebo-controlled clinical trial.
Author(s): Furey ML, Drevets WC.
Affiliation(s): Mood and Anxiety Disorders Program, National Institute of Mental Health, National
Institutes of Health, Bethesda, MD 20892, USA. mfurey@mail.nih.gov
Publication date & source: 2006, Arch Gen Psychiatry. , 63(10):1121-9
CONTEXT: The need for improved therapeutic agents that more quickly and
effectively treat depression is critical. In a pilot study we evaluated the role
of the cholinergic system in cognitive symptoms of depression and unexpectedly
observed rapid reductions in depression severity following the administration of
the antimuscarinic drug scopolamine hydrobromide (4 microg/kg intravenously)
compared with placebo (P = .002). Subsequently a clinical trial was designed to
assess more specifically the antidepressant efficacy of scopolamine.
OBJECTIVE: To evaluate scopolamine as a potential antidepressant agent.
DESIGN: Two studies were conducted: a double-blind, placebo-controlled,
dose-finding study followed by a double-blind, placebo-controlled, crossover
clinical trial.
SETTING: The National Institute of Mental Health. Patients Currently depressed
outpatients aged 18 to 50 years meeting DSM-IV criteria for recurrent major
depressive disorder or bipolar disorder. Of 39 eligible patients, 19 were
randomized and 18 completed the trial.
INTERVENTIONS: Multiple sessions including intravenous infusions of placebo or
scopolamine hydrobromide (4 microg/kg). Individuals were randomized to a
placebo/scopolamine or scopolamine/placebo sequence (series of 3 placebo sessions
and series of 3 scopolamine sessions). Sessions occurred 3 to 5 days apart.
MAIN OUTCOME MEASURES: Psychiatric evaluations using the Montgomery-Asberg
Depression Rating Scale and the Hamilton Anxiety Rating Scale were performed to
assess antidepressant and antianxiety responses to scopolamine.
RESULTS: The placebo/scopolamine group showed no significant change during
placebo infusion vs baseline; reductions in depression and anxiety rating scale
scores (P<.001 for both) were observed after the administration of scopolamine
compared with placebo. The scopolamine/placebo group also showed reductions in
depression and anxiety rating scale scores (P<.001 for both) after the
administration of scopolamine, relative to baseline, and these effects persisted
as they received placebo. In both groups, improvement was significant at the
first evaluation after scopolamine administration (P< or =.002).
CONCLUSION: Rapid, robust antidepressant responses to the antimuscarinic
scopolamine occurred in currently depressed patients who predominantly had poor
prognoses.
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