Ketamine for OCD
At a recent scientific meeting, researcher Carolyn Rodriguez presented a randomized controlled crossover trial of ketamine in obsessive-compulsive disorder (OCD). In contrast to a previous negative study by Block and associates at the National Institute of Mental Health (NIMH), these investigators found that intravenous (IV) infusion of ketamine (0.5 mg/kg over 40 minutes) was associated with a larger reduction in obsessive-compulsive symptoms when compared with saline infusion. These effects were rapid in onset and persisted for approximately one week in 50% of the patients with OCD who had constant intrusive thoughts.
This dose of ketamine had previously been shown to induce rapid-onset improvement in depression and suicidal ideation in those with unipolar and bipolar depression. However, the improvement in obsessive-compulsive disorder symptoms appeared unrelated to any antidepressant effect because the individuals with OCD had minimal depressive symptoms at baseline.
The traditional pharmacological treatments for OCD are selective serotonin reuptake inhibitor (SSRI) antidepressants, which require high doses and weeks to months before the onset of full effect. In contrast, Rodriguez et al. found a 90% response rate to IV ketamine within 3 hours.
Ketamine is a blocker of the glutamate NMDA receptors, and these data suggest that targeting these receptors can induce rapid onset of positive effects in OCD. However, as is the case with the acute antidepressant response to ketamine in those with depression, the best ways to extend this therapeutic effect long-term remain to be determined.
Another blocker of NMDA receptors, the anti-Alzheimer’s drug memantine (Namenda), has been reported in open studies to show improvement in those with OCD as well. N-acetylcysteine, a substance found in health-food stores, likewise appears to re-regulate a hyper-responsive glutamatergic system in the nucleus accumbens by other mechanisms, and was also shown to have efficacy as an augmenting treatment in OCD in those who are inadequately responsive to SSRIs in a 2012 article by Afshaw et al.
Editor’s Note: Taken together, the data with ketamine, memantine, and N-acetylcysteine suggest that glutamate-based mechanisms are involved in OCD and may provide an alternative target for therapeutics in addition to serotonin.
