Reports from the 51. ACNP Congress — II. Is Ketamine Effective in Obsessive-Compulsive Disorder?

At the 51st Congress of the American College of Neuropsychopharmacology (ACNP), 2nd – 6th December 2012 in Hollywood, Florida, Carolyn I. Rodriguez and colleagues  from Columbia University in New York reported yesterday the results of a small pilot study on the use of ketamine in obsessive-compulsive disorder (OCD). The very rapid antidepressant effects of the NMDA receptor antagonist ketamine in depressive disorders – especially in treatment-resistant patients – has been shown in numerous studies. This applies to both uni- and bipolar depression. A small open case series recently presented also suggests an effect of ketamine in OCD. This was confirmed in another open-label study, in which, however, the patients were multiply medicated and mostly also suffered from comorbid depression. Rodriguez and co-workers performed their double-blind, placebo-controlled crossover study in patients with OCD, who were not medicated and had to present with only mild depressive symptoms.

Ten patients received either saline or ketamine (0.5 mg/kg) as an infusion over 40 minutes. The two infusions were administered at intervals of at least one week, the order was randomized. The obsessive-compulsive symptoms as measured by the Yale-Brown Obsessive-Compulsive Scale (YBOCS), had to be at least a moderately severe with a score of > 16, whereas depressive symptoms as measured by the Hamilton Depression Rating Scale (HAMD)  had to score below 25. The OCD was quantified with the YBOCS before treatment and after seven days. To detect acute changes of obsessive thoughts, a visual analog scale was used (OCD-VAS). The depressive symptoms were rated before treatment and one and three days after infusion. The response to treatment was defined as a reduction in symptoms by at least 35% from baseline.

Before treatment, the mean YBOCS score was 27.1. The infusion of ketamine led to a very rapid reduction of obsessive thoughts. The OCD VAS scores were decreased three hours after infusion by 90%, 80% after one day, 60% after two days, 50% after three days and still 50% after one week. The score on the YBOCS was reduced by 50% after one week. The patients who had  received ketamine first and thus could be evaluated after 14 days,  showed  still a reduction in the YBOCS score of 40% at that time. The mean HAM-D score at baseline was only 4.2, it was reduced to 1.8 (p = 0.058).

The authors conclude from their results that ketamine – in addition to its antidepressant actions – has antiobsessive properties with a very rapid onset of action that persist in half of the patients for at least one week. The results are to be confirmed in larger patient numbers in parallel groups. The elucidation of the mechanisms that determine the broad efficacy of ketamine in mental disorders will hopefully lead to the development of new therapeutic strategies.


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