Motion Sickness' Drug Shows Rapid Antidepressant Effect

June 13, 2011 (Pittsburgh, Pennsylvania) — The antimuscarinic agent
scopolamine, which is typically used to treat motion sickness, appears
to produce a rapid antidepressant effect in patients with bipolar
depression (BD), new research suggests.
Results from a small 4-week randomized, crossover trial, presented
here at the 9th International Conference on Bipolar Disorders, show that
patients with BD who received intravenous (IV) scopolamine had
significantly decreased depression rating scores compared with patients
receiving placebo. Scopolamine also did not precipitate mania.
"We found that this IV infusion of the drug has long-lasting
antidepressant effects with very minimal side effects," lead author
Erika Frankel, research assistant in the Mood and Anxiety Disorders
Program at the National Institute of Mental Health (NIMH) in Bethesda,
Maryland, told Medscape Medical News.
"In addition, we've heard from patients a couple months out who
haven't been treated with any other type of drug that are still having
this antidepressant effect. There were really robust findings. So we'd
like to be able to get scopolamine out there and available to patients,"
said Ms. Frankel.
Fast-Acting Treatments Needed

According to the study, many patients with major depressive disorder
(MDD) or BD who find symptom relief after receiving conventional
antidepressant treatment do not experience improvement for up to 4 weeks
later.
"The need for improved therapeutics that more quickly and effectively
treat depression and BD remains critical," write the investigators.
In previous studies, the investigative group found that patients with
MDD and BD, and those with MDD only, had robust antidepressant effects
after using scopolamine.
"The principal investigator of those studies was first looking at
scopolamine for its cognitive effects and was surprised to find that it
actually decreased depressive symptoms," said Ms. Frankel.
The study included 14 outpatients with BD only who were experiencing a
major depressive episode, as indicated by a Montgomery Asberg
Depression Rating Scale (MADRS) score of 20 or greater.
They were randomly assigned to receive three 15-minute sessions of IV
scopolamine, 4 μg/kg, followed by 3 infusion sessions of a placebo
saline solution or the same treatments in reverse order over 4 weeks.
All treatment sessions occurred 3 to 5 days apart.
The MADRS, the Hamilton Anxiety (HAM-A) rating scale, and the Young
Mania Rating Scale (YMRS) were all administered before each infusion.
The results were then compared with those found in the investigators'
study of patients with MDD only (n = 38).
Significant Benefit

"For the MADRS scores in BD, a significant drug (P < .001) effect indicated that depression ratings were lower under scopolamine vs placebo," report the researchers.
"This difference was evident by the first post-drug assessment and
the magnitude of improvement did not differ from our previous group of
MDD patients," they add.
The HAM-A scores were also lower during the drug treatment phase than during the placebo phase (P < .05). Moreover, the YMRS scores did not significantly change across the study.
The findings are consistent "with evidence that the cholinergic
system is hypersensitive in BD and suggests that the cholinergic
hypersensitivity contributes to mood symptoms," write the study authors.
Ms. Frankel reported that treatment-related side effects were mild
and included dry mouth, blurred vision, and "a little bit" of
drowsiness, "but that wore off within 3 hours of the infusion." No
severe adverse effects were reported.
In addition, she said that the investigators are now assessing the effects of scopolamine in a nasal spray administration.
Cholinergic Mechanism

"This study reopens the question about the relevance of cholinergic
mechanisms in antidepressant response," Michael Thase, MD, professor of
psychiatry at the University of Pennsylvania School of Medicine in
Philadelphia and a course director for the International Conference on
Bipolar Disorders, told Medscape Medical News.
"Scopolamine administered intravenously in doses that get to the
brain rapidly and don't cause deal-breaking side effects or toxicities,
at least in relatively healthy younger to midlife populations, is
interesting. And this raises the possibility of other forms of delivery
of scopolamine, including transdermal and intranasal," said Dr. Thase.
He noted that scopolamine is a medication that has been around for a long time.
"People talked about cholinergic hypotheses and depression in the
'60s and '70s. But attention kind of fell away. Those at the NIMH are to
be commended for thinking of an alternate way in which an IV delivery
may make it possible to deliver this drug safely. And it does appear
that there's an effect there that warrants further investigation."
The study was funded by the NIMH. The study
authors have disclosed no relevant financial relationships, but a use
patent application for scopolamine as an anti-depressant agent has been
submitted by the NIMH. Dr. Thase has disclosed no relevant financial
relationships.

9th International Conference on Bipolar Disorder (ICBD): Poster P58. Presented June 9, 2011.