Elana Harris, MD, PhD Assistant Professor Division of Child and Adolescent Psychiatry Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio
Sergio V. Delgado, MD Professor Medical Director of Outpatient Services Division of Child and Adolescent Psychiatry Cincinnati Children’s Hospital Medical Center Department of Psychiatry and Behavioral Neuroscience University of Cincinnati Cincinnati, Ohio
Acknowledgments The authors acknowledge support from the National Institute of Mental Health 5K23MH100640-04 and helpful editorial comments from Dr. Jessica McClure.
Disclosures The authors report no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products.
Topiramate. Three 12-week RCTs examined topiramate augmentation at 100 to 400 mg/d in patients with OCD who had failed at least 1 previous trial of an SSRI. The earliest study was most encouraging: Y-BOCS scores decreased by 32% in the topiramate group but by only 2.4% in the placebo group.46 However, the other 2 studies found no difference in the final OCD symptom severity score between active treatment and placebo groups,47,48 and the use of topiramate, particularly at higher doses, was limited by its adverse effects.
Lamotrigine. Initially, lamotrigine augmentation of SSRIs in OCD did not appear to be helpful.49 More recently, several case studies reported that lamotrigine, 100 to 200 mg/d, added to paroxetine or clomipramine, resulted in dramatic improvement in Y-BOCS scores for patients with long-standing refractory symptoms.50,51 In a retrospective review of 22 patients who received augmentation with lamotrigine, 150 mg/d, 20 had a significant response; the mean decrease in Y-BOCS score was 67%.52 Finally, in a 16-week RCT, lamotrigine, 100 mg/d, added to an SSRI led to a significant decrease in both Y-BOCS score and depressive symptoms while also improving semantic fluency.53
Ketamine.Ketamine is drawing increased attention for its nearly instantaneous antidepressant effect that lasts for up to 2 weeks after a single infusion.54 In a study of 15 medication-free adults with continuous intrusive obsessions, 4 of 8 patients who received a single IV infusion of ketamine, 0.5 mg/kg, met the criteria for treatment response (>35% reduction in Y-BOCS score measured 1 week later); none of the patients who received a placebo infusion of saline met this criteria.55 A small open-label trial of 10 treatment-refractory patients found that an infusion of ketamine, 0.5 mg/kg, was beneficial for comorbid depression but had only a minimal effect on OCD symptoms measured 3 days post-infusion.56 A short-term follow-up on these patients revealed dysphoria in some responders.57
D-cycloserine. The idea of using a pharmacologic agent to increase the speed or efficacy of behavioral therapy is intriguing. Proof of concept was demonstrated in a study that found that giving D-cycloserine prior to computerized exposure therapy significantly improved clinical response in patients with acrophobia.58 However, using this approach to treating OCD netted mixed results; D-cycloserine was found to be most helpful during early stages of treatment.59,60
Table 3 outlines the mechanisms of action and common uses for NAC, memantine, ketamine, topiramate, lamotrigine, and D-cycloserine. Table 4 summarizes the literature on the efficacy of some of the augmentation strategies for treating OCD described in this article.
