Background
Currently, no pharmacological treatments for bipolar depression exist that exert rapid
(within hours) antidepressant or antisuicidal effects. We previously reported that
intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients
with treatment-resistant bipolar depression. The present study sought to replicate
this finding in an independent sample.
Methods
In this double-blind, randomized, crossover, placebo-controlled study, 15 subjects
with DSM-IV bipolar I or II depression maintained on therapeutic levels of lithium
or valproate received a single intravenous infusion of either ketamine hydrochloride
(.5 mg/kg) or placebo on 2 test days 2 weeks apart. The primary outcome measure was
the Montgomery-Asberg Depression Rating Scale, which was used to rate overall depressive
symptoms at baseline; at 40, 80, 110, and 230 minutes postinfusion; and on days 1,
2, 3, 7, 10, and 14 postinfusion.
Results
Within 40 minutes, depressive symptoms, as well as suicidal ideation, significantly
improved in subjects receiving ketamine compared with placebo (d = .89, 95% confidence interval = .61–1.16, and .98, 95% confidence interval = .64–1.33,
respectively); this improvement remained significant through day 3. Seventy-nine percent
of subjects responded to ketamine and 0% responded to placebo at some point during
the trial. The most common side effect was dissociative symptoms, which occurred only
at the 40-minute time point.
Conclusions
This study replicated our previous finding that patients with bipolar depression who
received a single ketamine infusion experienced a rapid and robust antidepressant
response. In addition, we found that ketamine rapidly improved suicidal ideation in
these patients.
Key Words
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Article Info
Publication History
Published online: February 02, 2012
Accepted:
December 5,
2011
Received in revised form:
December 1,
2011
Received:
October 26,
2011
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.