Subanesthetic doses of ketamine have demonstrated rapid, yet transient effects on patients with treatment resistant depression (TRD), which may be prolonged by repeated administration. In a recent single-site randomized double-blind crossover study, the antidepressant effects of a single ketamine dose, a series of ketamine infusions, and maintenance infusions were evaluated in forty-one participants with TRD. Participants received single infusions of ketamine or midazolam (an active placebo control). After relapse of depressive symptoms, participants received a course of six open-label ketamine infusions administered three times weekly over 2 weeks. Responders were those participants who had a 50% or greater decrease in their scores on the Montgomery-Asberg Depression Rating Scale (MADRS). Responders received four additional infusions administered once weekly (maintenance phase). At the primary efficacy endpoint (24 hours post infusion), a single dose of ketamine resulted in a significantly greater reduction in depressive symptoms compared to midazolam. Post-analysis revealed cumulative antidepressant effects with repeated infusions and doubling of the antidepressant response rate. Nearly 60% of participants met response criteria after repeated infusions, with a median of three infusions required before meeting criteria. Reductions in depressive symptoms were maintained among responders through once-weekly infusions, but maintenance infusions did not result in further alterations in MADRS scores. Results suggest that ketamine infusions have additive and sustained antidepressant effects. Future clinical research is needed to better establish optimal administration guidelines for efficacy.
Reference:
Phillips JL et al. Am J Psychiatry. 2019; Epub ahead of print. Abstract
For more information: