SSRIs remain the mainstay of pharmacological treatment for OCD. It is postulated that altered glutamatergic function can also be important in pathogenesis of OCD. Elevated glutamate levels are found in CSF and in Caudate. Caudate glutamate is shown to normalise after successful treatment with SSRI. Disrupting glutamatergic system can trigger OCD behaviour animals. Could Ketamine , a noncompetitive antagonist of the NMDA glutamate receptor benefit in OCD?
Carolyn I Rodriguez et al report the results of the first randomized, controlled trial of Ketamine in OCD. This was a double-blind, crossover study in 15 medication free adults ( on average for 3 years) with near constant obsessions.Patients with HAMD score more than 25 were excluded.The mean age of the sample was 34 years
Patients were randomized to one of two orders of infusions : arm A (Ketamine first and saline second) or arm B (saline first and Ketamine second). Each subject served as their own control.There was a minimum gap of 1 week between infusions. Ketamiane dose was 0.5mg/kg and infusion was given over 40min. A self rating scale measured changes in OCD.
Results: Study found significant benefit with ketamine.Those receiving Ketamine had lower mean estimated baseline OCD score at mid-infusion , 230 min , and 7 days post infusion.Half of those receiving Ketamine met respsone criteria ( 35% reduction in scores) at one week post infusion.This was 0% in placebo group.
Ketamine use was associated with symptoms of dissociation, distortions of time, ,unusual thought content and , conceptual disorganisation.
Conclusion: Ketamine has rapid anti-obsessional effects and it is also having significant carry over effects.
Limitations: Allowing more than one week in between infusions is more desirable. Small sample size. Blinding is difficult because of psychoactive effects of Ketamine, and thus self-rating forms may be subject to bias.
Summary of the article:
Rodriguez CI, Kegeles LS, Levinson A, Feng T, Marcus SM, Vermes D, Flood P, Simpson HB. Neuropsychopharmacology. 2013 Nov;38(12):2475-83.