Electrical Stimulation of the Internal Capsule for Intractable Depression
Condition: Depression
MeSH terms: Depression; Depressive Disorder
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will evaluate the safety and efficacy of deep brain stimulation in treating people
      with several and otherwise treatment-resistant depression.
    

Detailed description: 
      Despite the availability of effective treatments, a substantial portion of patients fail to
      recover from episodes of depression. Assuming a conservative rate of 20%, and given the
      prevalence of major depression in the general population, over 3.5 million Americans would be
      expected to manifest refractory illness if all those with depression received treatment.
      Although rarely used in the U.S., neurosurgical approaches to severely refractory depression
      have shown efficacy in a number of uncontrolled studies, primarily from European
      investigators. Deep brain stimulation (DBS) is a procedure that involves the use of thin
      wires to carry electric current to parts of the brain associated with producing depression
      symptoms. DBS has been effectively and safely used to treat movement disorders, such as
      Parkinson's disease, and may be beneficial in reducing depression symptom severity. This
      study will evaluate the safety and efficacy of DBS in treating people with severe and
      treatment-resistant depression.

      Study participation through follow-up will last up to three years. Participants will be
      allowed to remain on any pre-surgical medications or behavioral therapy programs throughout
      the study. Before surgery, all participants will undergo a series of initial tests and
      examinations that will include a physical and neurological examination; laboratory testing to
      screen for significant hematologic, hepatic, renal or endocrine abnormalities; and detailed
      psychological testing including tests of perception, learning, and memory.

      Implantation of all devices will be preformed at a single session. The patient will undergo
      local anesthesia for the implantation of the leads, and the implanted pulse generator will be
      implanted under general anesthesia. On the day of the surgery, participants will have a metal
      frame fixed to their heads for support during surgery. Using coordinates individually
      determined by preoperative MRI, a pair of tetrapolar leads will be inserted into the anterior
      limb of each internal capsule and fixed to the skull with a burr hole ring and cap. The leads
      will be inserted so that the stimulation sites span the dorsal-ventral extent of the anterior
      capsule or target the ventral half of the anterior capsule.

      After placement of the DBS system, the patient will be admitted to the hospital for overnight
      evaluation for possible complications of the procedure, including possible hemorrhage or
      infection. Postoperative evaluation will consist of physical and neurological examinations,
      postoperative CBC, electrolyte panel, plain x-ray studies of head, neck, and chest including
      a standard shunt series to ensure integrity of connections and to document positioning of
      stimulating hardware. A head CT scan will be obtained within 24 hours postoperatively to
      monitor for possible postoperative intracranial hemorrhage.

      If none of the above complications occur, the patient will be discharged home the following
      day with the DBS system off to allow resolution of the cellular reactions to electrode
      placement. Three weeks after placement of the DBS system, the patient will return to being
      the outpatient phase of testing the effects of stimulation.

      During the intensive outpatient phase of the study, each of the outpatient visits will last
      approximately two hours. These are anticipated to occur at from 1 to 5 day intervals. On each
      day, we will do a brief clinical interview and obtain structured ratings of depressive
      symptoms, mood and affect, possible side effects, and cognition.

      After completion of the two year study, patients will be given the choice of continued DBS,
      for a total of three years after implantation, or until the stimulator batteries fail.
      Patients will also be offered alternative treatment, outside of this study, including
      anterior capsulotomy, depending on availability given the patient's financial circumstances
      and insurance coverage, or further conventional therapy. Long-term patient follow-up will
      continue indefinitely where possible.

      During this study, patients will also be invited to undergo a series of three Positron
      Emission Tomography (PET) scans under a separate IRB protocol at Massachusetts General
      Hospital, to assess the effects of capsular stimulation on activity in brain circuits
      implicated in depression. Subjects' participation in this separate protocol is not a
      condition for entering the DBS study.
    

Intervention name(s): Deep Brain Stimulation System
Intervention type(s): Device
Intervention description(s): In DBS, thin wires are used to carry electric current to the parts of the brain involved in depression symptoms. These wires are implanted surgically and are attached to battery operated stimulators usually implanted in the chest. The study doctor will adjust the settings of the electrical stimulation to optimize treatment for each participant.
Other intervention name(s): Deep Brain Stimulation System from Medtronic, Inc.; Implantable Neurostimulator (INS)
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Deep Brain Stimulation; Treatment Refractory; Neurosurgery; Implantable Neurostimulator (INS); Internal Capsule