This application is in response to PA-99- 134 for Exploratory/Development Grants for Mental Health Intervention Research. The long-term goal of this research project is to reduce symptom severity and enhance quality of life for patients with severe and intractable obsessive-compulsive disorder (OCD). Despite advances in the pharmacological and behavioral therapies for OCD, a substantial number of patients fail to improve significantly following years of conventional as well as experimental interventions. For some patients, stereotactic neurosurgery (either cingulotomy or anterior capsulotomy) is the only promising option left. The available evidence suggests that these procedures may lead to enduring benefits and relatively few side effects in the majority of OCD patients with intractable disease. However, the effects of these ablative techniques on brain tissue and function are irreversible. Recently, a team of European investigators reported in the Lancet positive results in three of four intractable cases of OCD using bilateral deep brain stimulation (DBS) of the anterior limb of the internal capsule. Independent confirmation by a qualified psychiatric-neurosurgical team is crucial before it gains more widespread use; there are already indications from the Internet that numerous centers across the country are pursuing it. On the surface, it seems appealing, at least in contrast to other neurosurgical alternatives. Although DBS, like ablative surgery, is an invasive procedure with infrequent but serious risks, unlike ablative techniques, DBS is adjustable and partially reversible. If it fails, the device can be turned off, the inactive electrodes are usually left in place, but no permanent alteration in neuronal function is likely. The current project is designed to gather preliminary data on the effectiveness, safety, and tolerability of chronic electrical stimulation (DBS) via bilaterally implanted electrodes in the anterior limb of the internal capsules of six cases of 'malignant' treatment-refractory OCD that would otherwise be candidates for ablative neurosurgery. They will be followed for two years post surgery. All candidates for this procedure will have to pass review by an interdisciplinary internal review panel as well as two independent external reviewers. If shown effective, DBS might replace ablative neurosurgery, but should still be considered the intervention of last resort in the most profoundly ill and intractable cases of OCD.
