New Directions in Psychiatric Therapeutics

Two new therapies combine somatic and psychological approaches.

Posted Jan 08, 2020

Cocaine addiction and obsessive-compulsive disorder (OCD) are difficult to treat successfully. Recent papers published in the American Journal of Psychiatry describe successful treatment trials for each of these disorders that combine somatic and psychotherapeutic approaches. These two trials, while preliminary, are illustrative of advances in the development of new and effective treatments for psychiatric disorders.

Elias Dakwar, Frances Levin, and colleagues combined a single 40-minute intravenous infusion of ketamine with the initiation of a mindfulness-based relapse prevention program to treat individuals with cocaine dependence. Study participants spent five days on an inpatient unit where they received a ketamine infusion the day after daily sessions of the behavioral treatment were begun. Following discharge, the participants continued the mindfulness-based relapse prevention sessions twice a week for four weeks. During the final two weeks of the trial, 48% of those receiving the single ketamine infusion were abstinent from cocaine use compared with 11% of those who received an infusion of midazolam, which was used as an active control. In addition, the group that received ketamine was 53% less likely to relapse. This group also reported lower craving scores throughout the trial. This was a relatively small trial involving 55 participants, 27 of whom received ketamine; the findings will need to be replicated in larger studies. It is also unclear whether changes in cocaine or other drug use are sustained for longer periods of time. Nevertheless, this study provides hope for better treatments for cocaine dependence and potentially for other substance use disorders.   

In the second study, Lior Carmi, Joseph Zohar, and colleagues described results of a multi-site 6-week trial in which 99 individuals with OCD received either daily treatments (five days a week) with deep transcranial magnetic stimulation (dTMS) or sham dTMS stimulation following provocation of each individual’s OCD symptoms. The dTMS stimulation targeted the medial prefrontal cortex and the anterior cingulate cortex, regions that are thought to be involved in the brain circuitry underlying OCD. The researchers’ idea was to target the brain circuitry of OCD during times when the individual was having symptoms. Response to treatment was measured using a standardized rating scale for OCD. Participants in the active dTMS treatment group had significantly greater reductions in scores than the sham dTMS group. In addition, response rates (defined as a 30% or greater reduction in scores) were 38% in the dTMS group compared to 11% in the sham dTMS group at the end of treatment and 45% compared to 18% one month following treatment. The authors correctly indicate that more studies are necessary to refine the technique, although the results of this study are intriguing.

As we have described in previous posts, new pharmacological approaches are becoming available to treat psychiatric illnesses. In addition, new brain stimulation techniques are being developed. In the same issue of the American Journal of Psychiatry, Mark George reviewed advances in the use of TMS for the treatment of psychiatric disorders. Other brain stimulation approaches are also rapidly advancing.

With advances in new medication development and brain stimulation technologies, we anticipate significant progress in the treatments of various psychiatric disorders going forward. In addition, some of these new interventions may require only one or a few treatments when coupled with a limited number of psychotherapy sessions. The longer-term sustainability of the effects of these treatments will be important to determine in future studies.

This post was written by Eugene Rubin MD, PhD and Charles Zorumski MD.


Dakwar, E., Nunes, E.V., Hart, C.L., Foltin, R.W., Mathew, S.J., Carpenter, K.M., Choi, C.J., et al. (2019). A single ketamine infusion combined with mindfulness-based behavioral modification to treat cocaine dependence: a randomized clinical trial. Am J Psychiatry. 176: 923-930.

Carmi, L., Tendler, A., Bystritsky, A., Hollander, E., Blumberger, D.M., Daskalakis, J., Ward, H., et al. (2019). Efficacy and safety of deep transcranial magnetic stimulation for obsessive-compulsive disorder: a prospective multicenter randomized double-blind placebo-controlled trial. Am J Psychiatry. 176: 931-938.

George, M.S. (2019). Whither TMS: a one-trick pony or the beginning of a neuroscientific revolution? Am J Psychiatry. 176: 904-910.