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Repeated ketamine infusions have sustained antidepressant effects

Jennifer L. Phillips

Patients with treatment-resistant depression who responded to ketamine experienced sustained reductions in depressive symptoms with once-weekly maintenance infusions, according to study results published in American Journal of Psychiatry.

“Ketamine elicits rapid decrease in depressive symptoms, but its effects are not long lasting,” Jennifer L. Phillips, PhD, from the mood disorders research unit, The Royal’s Institute of Mental Health Research, Ottawa, Ontario, Canada, told Healio Psychiatry. “The goal of our study was to better understand how we can best administer ketamine to maximize and prolong its antidepressant effects.”

Researchers examined the antidepressant effects of ketamine infusions in a single-site, randomized double-blind crossover trial, which included 41 adults with treatment-resistant depression. In phase 1 of the study, patients were randomly assigned to single infusions of ketamine or midazolam (active control).

Participants who relapsed received a course of six open-label ketamine infusions administered three times a week over 2 weeks (phase 2). Those who responded to this course — as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) — then received once-weekly ketamine infusions for an extra 4 weeks (phase 3). The investigators measured change in MADRS scores and the Quick Inventory of Depressive Symptomatology–Self Report (QIDS-SR).

Analyses indicated that participants had significantly lower MADRS total scores after a single ketamine infusion compared with midazolam infusion. As compared with pre-infusion scores, participants had a larger average decrease MADRS total score 24 hours after ketamine infusion vs. midazolam (10.9 point decrease vs. 2.8). After 24 hours, 11 participants (27%) met antidepressant response criteria and two (5%) achieved remission.

After phase 2, more than half of participants (59%) met antidepressant response criteria and nine (23%) achieved remission. Overall, those who responded to ketamine had a mean reduction of 21.6 points in MADRS total score, according to the findings.

Of the 23 patients who continued to phase 3, Phillips and colleagues observed no further change in MADRS score when participants received once-weekly ketamine infusions.

“This is the first study that has shown we can decrease the frequency of the infusions once somebody has had a response—and still maintain the antidepressant effects,” Phillips said. “Through this study, we were able to test a much more practical way of administering ketamine in a clinical setting.”

There were no serious adverse events reported during the trial. In addition, participants showed significantly lower QIDS-SR total scores with ketamine than with midazolam at both 24 hours and 4 days post-infusion.

“Our findings indicate that the rapid antidepressant effects of ketamine can be sustained with repeated infusions. Further, individuals who do not respond to a single ketamine infusion may still respond over time with repeated infusions,” Phillips told Healio Psychiatry. “Once a patient has achieved an antidepressant response with ketamine, the frequency of infusions can be reduced yet the benefits are maintained. This therapy may offer hope to individuals whose depression continues despite trial of other medications.” – by Savannah Demko

Disclosure: Phillips reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.