Deep brain stimulation for intractable obsessive compulsive disorder: pilot study using a blinded, staggered-onset design

Abstract

Background: Prior promising results have been reported with deep brain stimulation (DBS) of the anterior limb of the internal capsule in cases with severe obsessive compulsive disorder (OCD) who had exhausted conventional therapies.

Methods: In this pilot study, six adult patients (2 male; 4 female) meeting stringent criteria for severe (minimum Yale-Brown Obsessive Compulsive Scale [Y-BOCS] of 28) and treatment-refractory OCD had DBS electrode arrays placed bilaterally in an area spanning the ventral anterior limb of the internal capsule and adjacent ventral striatum referred to as the ventral capsule/ventral striatum. Using a randomized, staggered-onset design, patients were stimulated at either 30 or 60 days following surgery under blinded conditions.

Results: After 12 months of stimulation, four (66.7%) of six patients met a stringent criterion as "responders" (> or =35% improvement in the Y-BOCS and end point Y-BOCS severity < or =16). Patients did not improve during sham stimulation. Depressive symptoms improved significantly in the group as a whole; global functioning improved in the four responders. Adverse events associated with chronic DBS were generally mild and modifiable with setting changes. Stimulation interruption led to rapid but reversible induction of depressive symptoms in two cases.

Conclusions: This pilot study suggests that DBS of the ventral capsule/ventral striatum region is a promising therapy of last resort for carefully selected cases of severe and intractable OCD. Future research should attend to subject selection, lead location, DBS programming, and mechanisms underpinning therapeutic benefits.

Trial registration: ClinicalTrials.gov NCT00057603.

Figure 1

Patients and raters were blind to treatment condition (sham vs. active) for the 90-day period starting with the first postoperative visit as noted by the yellow double arrow. (A) Three patients (S1, S4, and S6) randomized to active DBS at 1 month postimplantation (denoted by green arrow); (B) three patients (S2, S3, and S5) randomized to active at month 2 (denoted by green arrow). In (A) patients received 12 months of active DBS at 13 months postimplantation (marked by dotted vertical line), whereas in (B) patients received 12 months of active DBS at 14 months postimplantation (marked by dotted vertical line). Unbeknownst to subject 1 or the research treatment team, this individual's right-sided battery was depleted between 11 and 12 months (red triangle) following surgery. This event was closely followed by an exacerbation in OCD symptoms that normalized shortly after device replacement (green triangle). Subject 3 did not show a response until after major changes in DBS settings at week 8 status post surgery (see text for details). The reasons for the temporary worsening of subject 5 between months 10 and 12 postimplantation are unclear. Possibilities include impact of significant life events or setting changes at month 10 that improved mood but lowered threshold for panic attacks. These settings were further modified at month 12. DBS, deep brain stimulation; OCD, obsessive compulsive disorder; Y-BOCS, Yale-Brown Obsessive Compulsive Scale.