Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial.
J. Phillips, S. Norris, J. Talbot, Meagan Birmingham, T. Hatchard, Abigail Ortiz, Olabisi Owoeye, L. Batten, Pierre Blier
American Journal of Psychiatry March 29, 2019 DOI: 10.1176/appi.ajp.2018.18070834 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized double-blind crossover comparison with open-label extension Peer reviewed |
|---|---|
| Sample size | 41 |
| Population | Patients with treatment-resistant depression |
| Interventions | Ketamine Midazolam |
| Duration | Single infusion, 2-week course of thrice-weekly infusions, then once-weekly maintenance infusions |
| Topics | Depression Esketamine Ketamine |
| Citations | 416 |
| Key points | Repeated ketamine infusions produce cumulative and sustained antidepressant effects, with 59% of participants responding after a median of three infusions, and weekly maintenance infusions sustain the response. |
Abstract
Objective: Subanesthetic ketamine doses have been shown to have rapid yet transient antidepressant effects in patients with treatment-resistant depression, which may be prolonged by repeated administration. The purpose of this study was to evaluate the antidepressant effects of a single ketamine infusion, a series of repeated ketamine infusions, and prolongation of response with maintenance infusions.
Methods: Forty-one participants with treatment-resistant depression completed a single-site randomized double-blind crossover comparison of single infusions of ketamine and midazolam (an active placebo control). After relapse of depressive symptoms, participants received a course of six open-label ketamine infusions administered thrice weekly over 2 weeks. Responders, classified as those participants who had a ≥50% decrease in their scores on the Montgomery-Åsberg Depression Rating Scale (MADRS), received four additional infusions administered once weekly (maintenance phase).
Results: Compared with midazolam, a single ketamine infusion elicited a significantly greater reduction in depressive symptoms at the primary efficacy endpoint (24 hours postinfusion). Linear mixed models revealed cumulative antidepressant effects with repeated infusions and doubling of the antidepressant response rate. Fifty-nine percent of participants met response criteria after repeated infusions, with a median of three infusions required before achieving response. Participants had no further change in MADRS scores during weekly maintenance infusions.
Conclusions: Repeated ketamine infusions have cumulative and sustained antidepressant effects. Reductions in depressive symptoms were maintained among responders through once-weekly infusions. These findings provide novel data on efficacious administration strategies for ketamine in patients with treatment-resistant depression. Future studies should further expand on optimizing administration to better translate the use of ketamine into clinical settings.
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.