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Ketamine may help increase likelihood of abstinence in cocaine dependence

Elias Dakwar

A single ketamine infusion increased the likelihood that cocaine-dependent adults engaged in mindfulness-based behavioral modification would maintain abstinence, offered substantial protection from relapse and craving, and lowered the likelihood of cocaine use, according to a study.

Mindfulness-based relapse prevention (MBRP), a substance use disorder intervention, may be well-suited as a behavioral counterpart to ketamine, Elias Dakwar, MD, from New York State Psychiatric Institute, Columbia University Medical Center, and colleagues wrote in American Journal of Psychiatry.

“Efforts at behavioral modification are challenging for cocaine use disorder, with precarious motivation, craving, reactivity, and fixed perspectives impacting on the efficacy of behavioral interventions. Ketamine may improve many of these vulnerabilities,” Dakwar told Healio Psychiatry. “Further, it may serve as an experiential stepping-stone for mindfulness training specifically.”

Researchers examined whether a single ketamine infusion could improve treatment outcomes in 55 cocaine-dependent adults participating in mindfulness-based relapse prevention.

Participants were randomly assigned to receive a 40-minute IV infusion of ketamine (0.5 mg/kg) or midazolam (the control condition) over a 5-day inpatient stay. At this time, participants also began a 5-week course of mindfulness-based relapse prevention, with four sessions of MBRP provided on days 2 through 5 during the inpatient phase and the remaining sessions provided weekly.

The primary outcome was 2 weeks of abstinence measured via urine toxicology. Dakwar and colleagues also examined patients’ craving (via a visual analogue scale), mindfulness (via the Five-Facet Mindfulness Questionnaire) and stress sensitivity (via the Perceived Stress Scale) at each visit.

Overall 48.2% of participants in the ketamine group remained abstinent over the last 2 weeks of the trial compared with 10.7% in the midazolam group.

Participants were nearly six times more likely to achieve end-of-study abstinence in the ketamine group than those in the midazolam group (OR = 5.7; 95% CI, 1.3-25.1), according to the results.

Overall, 57.7% of participants who received ketamine went on to use cocaine or drop out vs. 92.9% of participants who received midazolam. The final main-effects model demonstrated that the midazolam group was almost eight times more likely to use cocaine than the ketamine group (OR = 7.8; 95% CI, 1.5-39.9) and there was no change in drug use over time. Also, craving scores were 58.1% lower in the ketamine group compared with the midazolam group (t = –2.57; 95% CI, 18.6-78.6) and there was no significant change in craving scores over time.

The ketamine group was 53% less likely to relapse than the midazolam group (HR = 0.47; 95% CI, 0.24-0.92), Dakwar and colleagues found. In addition, 6 months later, 44% of the participants in the ketamine group reported cocaine abstinence compared with none of the participants in the midazolam group during telephone follow-up interview.

“These sustained benefits, in some cases lasting several months, suggest the potential of ketamine for effecting long-term behavioral changes,” they wrote. “Further research is needed to replicate these results in a larger sample, as well as to clarify mechanisms, examine more rigorously the hypothesis of synergy between ketamine and behavioral treatments, and evaluate emerging pharmacotherapies comparable to ketamine.” – by Savannah Demko

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