By Harini Sarva, MD

Assistant Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Sarva reports that she is a consultant for Accorda Therapeutics, Amneal Pharmaceuticals, and Merz Pharma.

SYNOPSIS: Deep brain stimulation can be a treatment option for refractory obsessive-compulsive disorder, but the results are not significantly better than lesioning procedures. Small sample sizes, diverse targets of stimulation, and inconsistencies in rating scales are limiting factors in the studies of this modality.

SOURCE: Martinho FP, Duarte GS, Simoes de Couto F. Efficacy, effect on mood symptoms, and safety of deep brain stimulation in refractory obsessive-compulsive disorder: A systematic review and meta-analysis. J Clin Psychiatry 2020;81:19r12821.

This was a systematic review and meta-analysis of the available studies assessing the efficacy of deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD). While selective serotonin reuptake inhibitors and cognitive behavioral therapy remain first-line therapies, a small percentage of OCD patients require surgical intervention. The cortico-striato-thalamo-cortical network is targeted based on benefits seen in earlier lesioning procedures. Randomized clinical trials (RCTs) and observational studies, which enrolled OCD patients for DBS, were included. Primary measures included the Yale Brown Obsessive Compulsive Scale (Y-BOCS) and serious adverse events. Secondary measures included proportion of patients with complete response (Y-BOCS decrease by > 35%); proportion of patients in remission (Y-BOCS < 6); proportion of patients with a mood response; adverse events; dropouts; and predictors of response.

A search in EMBASE and other portals led to 1,817 papers being evaluated, and they were further narrowed by the authors to 46 papers. Eight were RCTs and 38 were observational studies, 13 of which were case reports. There was a total of 225 patients from these studies, and 46% were women. Average follow-up was 33 months. Limbic structures were stimulated in 33 studies, with the most common site being the subthalamic nucleus (STN); 42 reported bilateral DBS. Among the RCTs, 51% had complete response, with 57% of all subjects exhibiting a complete response to DBS. Only 8% of subjects in RCTs had achieved remission, with an overall remission rate of 5%. Among the different variables studied, the most consistent correlation was found between response in Y-BOCS and response in depression. Among the RCTs, there was a significant reduction in the weighted depression scores. There were 814 adverse events; 289 were psychiatric (the most common were hypomania, sleep issues, and irritability) and 202 were neurologic adverse effects (the most common were paresthesias, cognitive issues, and headache).

COMMENTARY

DBS has revolutionized treatment of various movement disorders, including Parkinson’s disease (PD), essential tremor, and dystonia. Its use is increasing in psychiatric disorders, such as OCD, which has demonstrated promise with more than 200 patients having the surgery, resulting in reduction in Y-BOCS scores. However, the overall results are only slightly better than lesional procedures. Therefore, for those seeking surgical intervention without implanted hardware, lesional procedures, such as capsulotomy, still may be a viable option. In addition, the targets have been diverse. No significant difference was found in efficacy between limbic and non-limbic targets, suggesting that the pathways are quite extensive and that targeting any region of these pathways can have an effect on OCD. However, the wide array of targets also leads to a greater side effect profile and difficulty in determining the most effective target. The listed neuropsychiatric side effects were not surprising, but because the vast majority of targets are smaller than for PD and other movement disorders, close monitoring for stimulation-related side effects is warranted. Limitations in the scale scores and the lack of streamlined scales for depression in this meta-analysis are other limiting factors. Further studies, with larger sample sizes and greater follow-up, are needed to determine the true efficacy of DBS in OCD and the role of treating depression on the total OCD response rates.