Deep Brain Stimulation: Clinical Findings in Intractable Depression and OCD

 

Friehs GM1, Carpenter L1, Tyrka A1, Malone D2, Rezai, AR2; Shapira NA3, Foote K3, Okun M3, Goodman WK3, Rasmussen SA1, Price LH1, Greenberg BD1

 

1 Psychiatry/Clinical Neurosciences, Butler Hospital and Rhode Island Hospital/Brown Medical School, Providence, RI, USA

2 Psychiatry/Neurosurgery, Cleveland Clinic Foundation, Cleveland, OH, USA

3 Psychiatry/Neurosurgery/Neurology, University of Florida, Gainesville, FL, USA

 

Gerhard_Friehs@Brown.edu

 
Abstract

In contrast to lesion procedures sometimes used for intractable depression (MDD) or OCD, deep brain stimulation (DBS) is nonablative, reversible, and

adjustable. More than 25,000 patients worldwide have undergone DBS for FDA-approved uses in movement disorders. We began studying the safety and efficacy of DBS of the ventral portion of the anterior limb of the internal capsule and adjacent dorsal ventral striatum ("VC/VS") in severe and highly refractory obsessive-compulsive disorder (OCD) in early 2001. This stimulation site was based on the target for the anterior capsulotomy lesion procedure, which overlaps that of subcaudate tractotomy (used in more than 1000 patients with highly refractory depression). Our collaborative OCD trial (Butler Hospital/Brown University, the Cleveland Clinic, and the University of Florida) has consistently found improvement in comorbid depressive symptoms in OCD patients undergoing DBS at this target. Improvement in affect and mood appeared to precede that in OCD itself. We therefore began FDA- and IRB-approved studies of VC/VS DBS in patients with severe and disabling depression, refractory to multiple adequate trials of medications, medication combination, psychotherapy, and bilateral ECT, which we term "intractable" MDD. We implanted the firstMDD patient in January 2003. Results of DBS in both populations will be presented.

 
1. INTRODUCTION

Deep brain stimulation (DBS) is nonablative, reversible, and adjustable. More than 25,000 patients worldwide have undergone DBS for FDA-approved uses in movement disorders. We began studying the safety and efficacy of DBS of the ventral portion of the anterior limb of the internal capsule and adjacent dorsal ventral striatum ("VC/VS") in severe and highly refractory obsessive-compulsive disorder (OCD) in early 2001, in close collaboration with B. Nuttin and colleagues (Leuven, Belgium), who originated stimulation at this target for OCD. This stimulation site was based on the target for the anterior capsulotomy lesion procedure, which overlaps that of subcaudate tractotomy (used in more than 1000 patients with highly refractory depression). Our collaborative OCD trial (Butler Hospital/Brown University, the Cleveland Clinic, and the University of Florida) has consistently found improvement in comorbid depressive symptoms in OCD patients undergoing DBS at this target. Improvement in affect and mood appeared to precede that in OCD itself. We therefore began FDA- and IRB-approved studies of VC/VS DBS in patients with severe and disabling depression, refractory to multiple adequate trials of medications, medication combination, psychotherapy, and to bilateral ECT, which we term "intractable" MDD. We implanted the first MDD patient in January 2003.

2. METHODS

After multidisciplinary assessment and independent review of diagnosis, prior treatment adequacy, and consent capacity, patients had DBS leads implanted bilaterally in the VC/VS. Six MDD patients have begun stimulation, and 5 have been chronically stimulated. Patients and raters were blind to stimulation condition for the first 3 months.

3. RESULTS

In the OCD patients, acute and chronic improvement in OCD and in depressive symptoms was seen. Of 10 OCD patients , 5 had a 25% or greater reduction in Yale-Brown Obsessive-Compulsive Scale severity at 6 months, as well as reduction in depression severity ratings. In five patients with depression without OCD, improvement in depressive symptoms and in functional status were observed. Gains in functioning appeared to precede improvement in depression ratings. All of the first 5 intractable MDD patients have shown improvement: 3 of 5 had > 50% improvement on the HDRS-28, one had a 23%, and the other a 17% reduction. HDRS-28 severity decreased from 31.4 +/- 3.42 (mean +/- SEM) to 15.8 +/- 2.91 overall after 3 months of DBS. Functional status on the Social and Occupational Functioning Assessment Scale (SOFAS) improved from 41.2 +/- 4.58 at baseline to 57.6 +/- 2.02 at 3 months. Most of the gain in SOFAS scores occurred during the first month of DBS. All 5 patients are undergoing continuing open stimulation. The first 3 patients have experienced stimulator battery failure, accompanied by symptom worsening. Symptoms improved when DBS resumed.

4. DISCUSSION AND CONCLUSIONS

We view these results as encouraging. This research is demanding, requiring considerable commitment by a highly trained psychiatric neurosurgery team and very close patient followup. Persistent adverse effects have been infrequent in both OCD and depression patients. Induction of transient, reversible hypomania has been the most significant adverse effect of stimulation. Stimulation-induced hypomania has become less frequent with changes in stimulation technique and addition of mood stabilizer medication. Additional efficacy and safety data will be presented.