Is Ketamine Almost Ready for Prime Time Use in Depression?

Although antidepressant medications are effective in 50-70% of patients with severe acute depression, they have a delayed onset of beneficial effect.  This is a major limitation of these medications, as it leaves patients vulnerable to an increased risk of suicide, and increases the chances of premature discontinuation of therapy.

In 2006 I described the dramatic effect of intravenous ketamine in immediately curtaining severe depression.  At that time, the investigators realized how dramatic their findings were, and emphasized that the drug should only be studied in a research setting and not used clinically, until more data are available.  Well, now there’s more data – a study reported in the Archives of General Psychiatry on the use of ketamine in treatment-resistant bipolar disease.

Over a 3-year period, 18 patients with bipolar depression who had failed to respond to lithium or valproate medication were given infusions of either ketamine or placebo, on two separate days two weeks apart; this was a double-blind, cross-over study.  Their depression was rated, using 4 different scales, including the Hamilton Scale for Depression, at frequent intervals, for up to 14 days after infusion. 

Within 40 minutes the ketamine infusions were associated with a significant improvement in depressive symptoms, compared with the placebo infusions.  The improvement was maximum at day 2, and remained significant through day 3.  Overall, 71% of the participants responded to ketamine compared with 6% to placebo, at some point in the trial.  There were no serious adverse effects reported.

This encouraging study opens the way for further research to evaluate the relevance of intravenous administration in avoiding passage (and hence breakdown) of ketamine through the liver, and how the benefits of the drug can be extended for long-term effectiveness.  Still some years to go, I fear.