Deep Brain Stimulation and Obsessive-compulsive Disorder

Overview

Obsessive-compulsive disorder (OCD) is a relatively common psychiatric condition, which is classically treated by antidepressant medications in combination with psychotherapies. However, both these conventional therapeutic approaches fail to sufficiently improve obsessive-compulsive symptoms in 20-30% of cases. From these considerations, deep brain stimulation (DBS), as a reversible and adjustable surgical procedure, has recently been introduced in the field of resistant OCD. DBS currently uses electrodes with four contacts on each lead, which are bilaterally implanted into the chosen brain structure. DBS consists of the delivery of a high-frequency current through the quadripolar electrodes connected to a battery powered pulse-generating device. Several clinical investigations have shown that DBS, primarily targeting either the ventral striatum (VS) or the subthalamic nucleus (STN), as brain sites of interest because of their particular involvement in the production of OCD symptoms, is able to produce an approximately 40% or greater reduction in clinical symptom intensity in severely chronic and incapacitating forms of OCD. These promising findings lead to propose a comparison of the efficacy, safety and tolerability of DBS choosing either the VS or STN as brain target by conducting a large controlled trial and including a medico-economic analysis for assessing the classical cost/efficacy ratio. In this way, the present study is expected to promote and highlight the importance of DBS, as an effective, safe, well-tolerated and cost-relevant surgical approach for the management of resistant OCD.

Obsessive-compulsive disorder (OCD) is a relatively common psychiatric condition with an estimated lifetime prevalence of 2-3 % of the general population. It is generally characterized by a chronic course leading to a profound impairment in psychosocial functioning and to a marked deterioration in quality of life. Today, the well-established efficacy of antidepressants, acting preferentially by blocking serotonin reuptake, in addition to psychological treatments, have considerably changed the poor prognosis of the illness. However, both conventional therapeutic approaches failed to substantially alleviate obsessive-compulsive symptoms in 20-30% of cases. Deep brain stimulation, as a reversible and adjustable surgical procedure, has recently been introduced in the field of OCD, primarily targeting either the ventral striatum (VS) or the subthalamic nucleus (STN) and leading to an approximately 40% or greater reduction in clinical symptom intensity from baseline levels in severely chronic and resistant forms of OCD. These promising findings lead to propose a comparison of the efficacy, safety and tolerability of DBS choosing either the VS or STN as brain target by conducting a multicenter, parallel-group, randomized, single-blind trial over a 13-month follow-up period. For this purpose, a total population of 28 OCD patients who meet the currently used operational criteria for defining therapeutic resistance will be recruited. The surgical procedure will consist in the implantation of stimulation electrodes with four contacts on each lead, which are stereotactically and bilaterally implanted into the targeted brain structure under local anesthesia. Per-operative, single-unit electrophysiological recordings of the neuronal activity will be performed using five parallel microelectrodes and serving as guide for the implantation of both definitive electrodes. They will be connected to a battery powered pulse-generating device five days later under general anesthesia. Thereafter, psychiatric assessments including both the Y-BOCS ("Yale-Brow Obsessive-compulsive scale") and PI ("Padua Inventory") for measuring OCD symptom severity, the BAS ("Brief Anxiety Scale"), MADRS ("Montgomery and Asberg Depression rating Scale") and HAD ("Hospital Anxiety and Depression Scale") for determining anxiety and/or depressive symptom intensity, and the CGI ("Clinical Global Impression") rating scales for evaluating global symptom severity and treatment response will be performed every 3 months beyond the one-month postoperative free-stimulation period. This will be coupled with a large battery of neuropsychological tests exploring all executive functions in combination with precise medical records of side effects for appreciating safety/tolerability of DBS. A cost-effectiveness analysis, as a formal method of comparing DBS and classical therapeutic strategies with regard to their respective resource utilization (costs) and outcomes (effectiveness) will also be carried out. Therefore, the present study may contribute to highlight the special interest of DBS, as an effective, safe, well-tolerated and cost-relevant surgical approach for the management of resistant OCD.