Maintenance Ketamine Infusions for Treatment-Resistant Depression

Multiple studies have shown the benefits of using ketamine for treatment-resistant depression. Typically, the spacing of the ketamine infusions have been either two or three times per week. However, one recent study published in 2019 in the American Journal of Psychiatry showed that the reduction in depression symptoms were maintained with once-weekly infusions.

This study was conducted at The Royal’s Institute of Mental Health Research in Ottawa from 2013 to 2017. Forty-one patients between the ages of 18-65 participated. In the first phase, researchers evaluated the effects of a single dose of ketamine, a series of doses, and how the effects lasted.

Researchers found that compared to placebo, ketamine greatly decreased depression symptoms 24 hours after the infusion. Just 24 hours after the single ketamine infusion in the first phase, 27% of the participants experienced an improvement in their depression symptoms, and 5% went into remission (i.e. didn’t have any more depression symptoms!).

Responders to the treatment were classified to have a greater than or equal to 50% reduction of their Montgomery-Åsberg Depression Rating Scale (MADRS) score. Although 68% were classified as nonresponders (i.e. experienced no effect) 24 hours after the infusion, these patients still had a 6.7 average point reduction of their MADRS score.

In the second phase of the study, responders received six, three times a week ketamine infusions. After six infusions, 59% of the patients had improved depression syymptoms and 23% achieved remission. Responders had an average decrease of 21.6 points in the MADRS score.

In the third phase, four additional infusions were administered weekly in those patients who had a 50% improvement in their MADRS scores. Throughout this maintenance phase, 91% of the patients experienced improved depression symptoms. Of note, there were no reports of craving or drug-seeking behavior among the participants during the trial or in the follow-up period.

This is the first randomized double-blind crossover study designed to determine the superior antidepressant effects with a single ketamine infusion compared with placebo. This is also the largest study to date to report the maintenance of antidepressant effects in responders when the frequency of infusions was reduced to once weekly.

After we read this study, a few questions came up for us? Like what could happen if the dose of ketamine was at a higher dose? In this trial, the dose was consistently 0.5 mg/kg throughout all infusions. At Reset Ketamine, we use progressively escalating doses for our patients, depending upon our patient’s vital signs and effect from ketamine. In addition, by incorporating the bio-psycho-social-spiritual model, preparation, intention, set & setting, and integration, we have seen improvements that can be maintained for an even longer period of time.

What do you think of this study? Have questions? Please contact with any questions or comments and share with a friend!

Reference:

Phillips, J. L., Norris, S., Talbot, J., Birmingham, M., Hatchard, T., Ortiz, A., . . . Blier, P. (2019). Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial. American Journal of Psychiatry. doi:10.1176/appi.ajp.2018.18070834

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