Brain Stimulation for Treatment Resistant Depression
Clinicians believe deep brain stimulation (DBS)—originally developed to treat chronic pain, tremor, and epilepsy—may be suitable for treatment-resistant depression, as well. Cusin and colleagues define DBS as a reversible, neurosurgical procedure, in which electrodes are implanted at specific locations within the brain, and send electrical impulses varying in intensity and frequency. A safe procedure, DBS is approved by the Food and Drug Administration (FDA) for the treatment of tremor, Parkinson’s disease, dystonia, and, in 2009, obsessive-compulsive disorder (OCD).1 Cusin and colleagues describe the short-term side effects of DBS as headache, incontinence, postoperative confusion, fatigue, memory difficulties, weight gain, and in three to four percent of cases, seizures.1
Research has shown that DBS can induce mood changes when certain locations are targeted, a discovery that ultimately led to continued examination of DBS and psychiatric disorders.1 Anterior capsulotomy, a procedure targeting the anterior limb of the internal capsule,1 was first performed as a treatment of severe OCD in France in 1949 by Tailarach and colleagues. Cusin and colleagues state that anterior capsulotomy may be performed in two ways: thermocapsulotomy by neurosurgery or minimally-invasive gammacapsulotomy.1 In Sweden in 1961, Leksell and colleagues conducted a study of 116 patients who underwent thermocapsulotomy and reported a beneficial response in 50 percent of patients with OCD and 48 percent of patients with major depressive disorder.
More recently, in 2009, Malone and colleagues conducted a trial of DBS at the intersection of the ventral capsule and the ventral striatum for the treatment of major depressive disorder (MDD). Fifteen patients participated, meeting the criteria of five or more years of MDD and a history of failed trials with antidepressants and combination therapy.4 Malone and colleagues found no adverse effects on patients’ cognitive functions and reported the treatment to be well tolerated, and currently a clinical trial of the same population is underway to examine the effectiveness of active stimulation.4
Cusin and colleagues state that adhering to strict patient-selecting criteria is critical to the treatment’s success, and outline several factors that should be considered. First, the patient must meet the DSM-IV criteria for MDD, which also must be the patient’s primary disorder. Severity of the MDD must be chronic and debilitating, typically exceeding a duration of five years, and causing the patient to function on a low level and have a very poor quality of life.1 Second, the patient must have previously undergone multiple forms of treatment, including psychotherapy, pharmacotherapy, combination therapy, and electroconvulsive therapy, all of which have not shown significant improvement of symptoms.1 Patients with co-occurring psychiatric disorders, such as bipolar disorder, psychosis, substance abuse, and personality disorders do not qualify for DBS treatment. Also, patients with underlying medical disorders, such as brain lesions, central nervous system injuries, and seizure disorders, do not qualify either.1 Finally, and importantly, patients must have access to acceptable postoperative care, including a primary care doctor, a psychiatrist, and a psychotherapist.1
The procedure itself is described as “complex.”1 First, a head frame is used to obtain images of the patient’s brain, which allows for planning of electrode placement. The procedure uses a 3391 brain lead that is 1.27 mm in diameter and has four electrode contacts that are 3 mm long.1 The leads are implanted bilaterally in the ventral capsule and the ventral striatum, and during the process, the patient remains awake for the purpose of verbal feedback.1 Once the leads are in place, a test simulation is conducted in order to identify the improvement in mood. Next, postoperative imaging is taken to ensure correct placement.1 Finally, the patient is placed under general anesthesia and two neurostimulators are implanted under the clavicle in the chest area, and are connected to the electrodes with wires planted subcutaneously.1
After a several week resting period, the patient’s stimulation parameters are set.1 Usually, this process is time consuming, and can last hours over a period of several days as no set of parameters works for each patient. Follow-up during the first six months is crucial to achieving effective stimulation parameters, and other therapies should be coordinated during this time for close monitoring.1 Stimulation is delivered consistently until battery depletion, which is usually once per year; however, replacing batteries has not shown to cause a lapse in treatment.1
Therefore, Cusin and colleagues state that DBS is a reasonable treatment for chronic cases of MDD.1 Research has shown improvements in patients with OCD and MDD when treated with anterior capsulotomy, and the ventral capsule and ventral striatum positioning for electrodes in patients with MDD has been identified through studies of the OCD/MDD population.1 Cusin and colleagues report that the most favorable risk to benefit ratio applies to patients with MDD, and further guidelines for safety and success are currently being established.1
 Cusin, C.; Evans, K.C.; Carpenter, L.L.; Greenberg, B.D.; et al (2010). Deep Brain Stimulation for Treatment Resistant Depression: The Role of the Ventral Capsule/Ventral Striatum. Psychiatric Annals 40(10): 477-484.
 Talairach J, Hecaen H, David M. Lobotomie prefrontal limitee par electrocoagulalion des fibres thalamo-frontales a leur emergence du bras anterieur de la capsule interne. In: Masson LV, ed. IV. Congres Neurologique International. Paris, France; 1949:141.
 Heiner T. Treatment of Mental Disorders With Frontal Stereotaxic Thermo-Lesions: A Follow-Up Study of 116 Cases. Copenhagen: Munksgaard; 1961.
 Malone DA, Dougherty DD, Rezai AR, et al. Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biol Psychiatry. 2009;65(4):267-275.