CAN EXPOSURE-BASED CBT EXTEND IV KETAMINE’S EFFECTS IN OCD? AN OPEN-LABEL TRIAL

Abstract

Abtract Introduction A single subanesthetic intravenous (IV) dose of ketamine leads to rapid anti-obsessional effects in obsessive-compulsive disorder (OCD) patients with near-constant intrusive obsessions, but these effects usually do not persist. We tested whether a brief course of exposure-based cognitive behavioral therapy (CBT) could extend ketamine’s effects in a two week pilot open trial and if this effect was maintained (without additional treatment) two weeks later. Our rationale was: 1) ketamine is reported to enhance plasticity and extinction learning in rodents, and 2) enhanced extinction learning may facilitate CBT gains, as reported in trials that combined CBT with agents thought to facilitate extinction learning (e.g. D-cycloserine). Mimicking those trials, CBT was abbreviated (i.e. 10 one-hour exposure sessions) but delivered during the putative time interval when ketamine facilitates extinction learning (within 14 days). Methods Ten unmedicated OCD outpatients (aged 18-55) with near-constant intrusive obsessions (>8 hours/day) and at least moderate symptoms (Y-BOCS score ≥16) were recruited. Exclusion criteria included severe depression (HDRS >25), current CBT, and comorbid psychiatric or medical conditions that made participation unsafe. In an open-label design, participants received a single 40-minute IV infusion of ketamine (dose=0.5 mg/kg), followed by 10 one-hour exposure sessions delivered over two weeks. The CBT treatment was planned in a 90-minute session the day before the ketamine infusion. At baseline, during the infusion, at 20, 90, 110, 230 minutes post-infusion, patients rated their obsessional severity using the OCD-VAS. At baseline and weekly for four weeks post-ketamine, an independent evaluator, blind to study design, evaluated patients using the Y-BOCS, which appraises obsessive and compulsive symptoms over the prior week. Treatment response was defined a priori as ≥35% Y-BOCS reduction at week 2. Y-BOCS outcomes were analyzed using mixed-effects regression to model symptoms as a function of time. Results Of the 10 patients who started ketamine, nine completed the infusion. Eight reported a rapid reduction in obsessive severity as measured by the OCD-VAS, which persisted up to 230 minutes post-infusion in seven patients. Eight completed the 10 hours of exposure and the two week follow-up and were included in the Y-BOCS analyses. From baseline to four weeks post-infusion, OCD severity, as measured by the YBOCS, was significantly decreased over time (F=14.36, df=4,28, p Conclusions These results corroborate prior findings that IV ketamine can rapidly reduce obsessions in unmedicated OCD patients. The data suggest that a brief course of CBT may help some individuals maintain the improvement they experienced from ketamine; however, this needs to be formally tested in a randomized controlled trial to determine whether the improvement seen after two weeks of CBT is due to the addition of CBT, or whether the effects of ketamine persist longer in some than previously described.