Deep Brain Stimulation (DBS) in Treatment Refractory Obsessive-Compulsive Disorder (OCD)

The aims of this study are to determine the efficacy of Deep Brain Stimulation in treatment refractory OCD. This is in tandem with functional neuroimaging and neuropsychological assessment to evaluate the impact of DBS implantation on neuropsychological, magnetoencephalographic functioning, and intracerebral blood flow and metabolism. There are no wash-out or break periods in between each phase of the treatment when participants do not undergo any of the treatments. The study will consist of 3 sequential treatment phases. i)After electrode implantation, participants will enter an open phase of 8 months during which they will be evaluated every 2 weeks for severity of symptoms and optimal stimulation parameters. Once an initial and substantial decrease (6 points) in Y-BOCS score has been obtained, a standardized CBT program will be added. Treatment with CBT will consist of weekly individual sessions of 60 minutes for 24 weeks. ii)After the open phase, participants will enter a 1-month, double blind, sham-controlled phase. Participants will be randomly allocated to 2 periods of 2 weeks with the stimulators blindly turned on (active stimulation) in one period and turned off (sham stimulation) in the other period. Block randomization will be used with computer-generated random sequence, providing adequate concealment. Participants will be assessed 3 times (refer to outcome measures below), at baseline, after a 2-week period of active or sham stimulation, and after the second 2-week period of reversed active or sham stimulation). The assessor will be blinded to stimulation conditions. Treatment with CBT will consist of weekly individual sessions of 60 minutes for 24 weeks. The CBT sessions will focus on exposure and response prevention, as well as addressing avoidance. The CBT sessions will be undertaken by a psychiatrist skilled in CBT, which may be either one of the study psychiatrists or a treating psychiatrist. The CBT will not be manualized and will be treatment as usual CBT for severe OCD. In terms of psychotropic medication, participants will continue with their prescribed medication for OCD without change for 2 months prior to implantation and with continuation during the first 2 phases of the study (that is for 9 months after implantation). iii)The ensuing maintenance phase will last for 12 months, during which participants will be evaluated, utilising outcome measures below, at 3-month intervals. The stimulators will be turned on for all participants, and stimulation parameters will be adjusted if necessary. Surgical Procedure Implantation of the electrodes will be performed according to standard stereotactic procedures using frame-based magnetic resonance imaging for target determination. All patients will undergo bilateral implantation of 4 direct-contact electrodes (model 3389; Medtronic Inc, Minneapolis, Minnesota), with contact points 1.5-mm long and separated from adjacent contacts by 0.5 mm. The MEDTRONIC Deep brain stimulation lead Model 3389 has four platinum iridium electrodes, which are spaced 0.5 mm apart. The contacts are coded from 0 (ventral) to 3 (dorsal) and are independently programmable. Target coordinates for the electrode tip are 7 mm lateral to the midline, 3 mm anterior to the anterior border of the anterior commissure, and 4 mm inferior to the intercommissural line. Electrodes will be implanted following the anterior limb of the internal capsule into the target nucleus, with an anterior angle of approximately 75° to the intercommissural line. Electrodes will be connected via subcutaneous extensions to stimulators (Activa, Medtronic Inc) placed bilaterally in an infraclavicular pocket under general anaesthesia. Postoperative frame-based computed tomography images or radiographs will be used to verify the position of the implanted electrodes. Electrode and therapeutic impedances of the DBS device will be measured intraoperatively. Stimulation parameters Stimulation parameters will follow standard parameters, which will not be exceeded, hence: to a frequency of 120-180 Hz; and a pulse width of 60 to 90 microseconds. Optimization will be limited to changes in active contact points and voltage, ranging to a maximum of 6.0 V. Stimulation will be cyclic during the 8 month open phase and twelve month maintenance phases, as tolerated in terms of obsessive-compulsive symptomatology- 30 seconds on, 2 minutes off, 30 seconds on, 2 minutes off- to maximise battery life. If cyclic stimulation is poorly tolerated in terms of obsessive-compulsive symptomatology, then continuous stimulation during the open and maintenance phases will be utilised. The cyclic or continuous active stimulation utilised at the end of the 8 month open phase will continue during the 1-month, double blind, sham-controlled phase.