Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression

By J. Murrough, A. M. Perez, S. Pillemer, J. Stern, M. Parides, M. aan het Rot, K. Collins, S. Mathew, Dennis S. Charney, D. Iosifescu. Biological Psychiatry, 2012

746 citations recorded by the source corpus.

Background Ketamine is reported to have rapid antidepressant effects, however there is limited understanding of the time-course of ketamine effects beyond a single infusion. A previous report including 10 participants with treatment-resistant major depression (TRD) found that six ketamine infusions resulted in a sustained antidepressant effect. In the current report, we examined the pattern and durability of antidepressant effects of repeated ketamine infusions in larger sample, inclusive of the original. Methods Participants with TRD (n=24) underwent a washout of antidepressant medication followed by a series of up to six intravenous (IV) infusions of ketamine (0.5 mg/kg) administered open-label three times weekly over a 12-day period. Participants meeting response criteria were monitored for relapse for up to 83 days from the last infusion. Results The overall response rate at study end was 70.8%. There was a large mean decrease in Montgomery–Asberg Depression Rating Scale (MADRS) score at two hours following the first ketamine infusion (18.9±6.6, p<0.001) and this decrease was largely sustained for the duration of the infusion period. Response at study end was strongly predicted by response at four hours (94% sensitive, 71% specific). Among responders, median time to relapse following the last ketamine infusion was 18 days. Conclusions Ketamine was associated with a rapid antidepressant effect in TRD that was predictive of a sustained effect. Future controlled studies will be required to identify strategies to maintain an antidepressant response among patients who benefit from a course of ketamine.

Subfields: Biological Psychiatry, Cellular and Molecular Neuroscience, Pharmacology

View Paper: https://www.semanticscholar.org/paper/e410b9b1cd6a75ed6911f91ad3552ab079929186

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biological Psychiatry

1. S. Mathew
2. G. Sanacora
3. Michael Berk
4. C. Nemeroff
5. Dennis S. Charney

In Cellular and Molecular Neuroscience

1. C. Nemeroff
2. G. Sanacora
3. Dennis S. Charney

In Pharmacology

1. S. Mathew
2. C. Nemeroff
3. G. Sanacora
4. Dennis S. Charney
5. L. Monteggia

Citations in the corpus

• Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation (2021, background): “The short-term efficacy of intravenous racemic ketamine has invited the need in most cases for repeated dosing to sustain the therapeutic benefit (53).”
• Psychedelics Promote Structural and Functional Neural Plasticity (2018, background): “, 2012), even exhibiting efficacy in treatmentresistant populations (DiazGranados et al., 2010; Murrough et al., 2013; Zarate et al., 2006).”
• Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial (2013, positive): “The raters were experienced research staff extensively trained in the use of the instruments, and the MADRS rating conventions were pilot tested in prior ketamine studies in treatment-resistant major depression (13, 22).”