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Ketamine for Bipolar Depression

Summary and Comment |
July 9, 2012

Ketamine for Bipolar Depression

  1. Steven Dubovsky, MD

The drug may prove useful acutely in severely depressed patients who need an immediate response.

  1. Steven Dubovsky, MD

Evidence is accumulating for ketamine's acute antidepressant effect lasting up to a few weeks in unipolar depression (see JW Psychiatry Jan 3 2011). In a new, randomized, double-blind, crossover, placebo-controlled study, researchers examined its effect on depressive symptoms in 15 hospitalized patients (mean age, 47) with bipolar I or II disorder and current depression (average duration, 21 months) who had not responded to therapeutic doses of lithium or valproate. Participants, who were maintained on the mood stabilizer, received single intravenous infusions of ketamine and placebo 2 weeks apart. A patent application involving an author has been filed.

Ketamine was significantly better than placebo in reducing depression rating scale scores at 40 minutes through 2 to 3 days, depending on the analysis. The medium-to-large effect size was slightly greater in the first 40 minutes through 230 minutes (0.85–0.89) than 1 day after the infusion (0.70). The day after ketamine was infused, 29% of patients met remission criteria. Suicidal ideation on three different rating scales decreased significantly with ketamine, with a distinctly large effect size (0.94–2.09). Depression relapsed at an average of 4.5 days after the infusion. No meaningful differences were seen between intent-to-treat and completer analyses (11 of the 15 patients were completers).

Comment

As in unipolar depression, ketamine in severe bipolar depression can have rapid antidepressant and antisuicidal ideation effects. However, this short-term study could not address the risk for induction of mania and cycling, and ongoing treatment with ketamine may not be practical. The drug may prove useful acutely in severely depressed patients who need an immediate response until other treatments start to work. Other modulators of the N-methyl-d-aspartate receptor may prove easier to use long-term in unipolar and, possibly, bipolar depression.

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