Psychosurgery has a decidedly checkered history, having received a bad name for itself after Walter Freeman developed trans-orbital prefrontal lobotomy and propagated its use across the United States until the 1950s (for background, see the book The Lobotomist by Jack El-Hai). But more sophisticated versions of psychosurgery continue to be used, and DBS is a neurosurgical procedure that can be seen as a 21st century alternative to psychosurgery. In DBS, an electrode is placed at 1 mm accuracy into one of several specific areas of the brain implicated in the neurocircuitry of mood and anxiety disorders. The electrode is connected externally to bilateral subcutaneous generators that can then be adjusted by the clinician. DBS is reversible in that the stimulator can be turned on or off, and the output of the device and stimulation can be controlled. This also allows researchers to create sham conditions that allow for blinded placebo controlled trials, a method that is unavailable for practical and ethical reasons in lesioning operations. However, DBS still requires neurosurgery, and thus has the potential for serious medical and neurological side effects. DBS is currently FDA approved to treat Parkinson’s disease and essential tremor. Based on research that an area of the brain named the subgenual cingulate region (Brodmann area 25) is metabolically overactive in treatment resistant depression, Helen Mayberg et al. used this target for deep brain stimulation in six patients with treatment resistant depression. Four out of the six patients had sustained remission from their depression, and the antidepressant effects were associated with changes in their brain PET scans (Mayberg, et al, Neuron 2005; 45:651-660). Recently, there has been a flurry of interest and research in DBS for both treatment resistant depression and OCD, targeting specific areas of the brain involved in these disorders, including the anterior limb of the internal capsule, the subgenual cingulate region (extensively researched by Mayberg and colleagues), and the ventral internal capsule/ventral striatum, among others. (For a review paper of DBS in psychiatric disorders, see Larson P.S, Neurotherapeutics, 2008; 5:50-58.) Two device companies (Medtronic and St. Jude) are in the process of investigating DBS in severe treatment resistant depression in large scale multicenter, sham-controlled trials that are actively recruiting participants.

The New Brain Devices Vagus Nerve Stimulation: Approved for treatment resistant depression, but efficacy has been questioned; not covered by insurance. Deep Brain Stimulation: Deep electrode placement, requires surgery; investigational. Magnetic Seizure Therapy: Alternative to ECT; seizure induced by magnetic field rather than electric shock; investigational. Cortical Stimulation: Electrodes implanted  on top of cortex; investigational.

 

MST is designed as an alternative to ECT (electroconvulsive therapy). Whereas ECT uses a brief electrical stimulus to induce a seizure, thereby easing depressive symptoms, MST uses a magnetic stimulus to accomplish the same goal. The potential advantage of MST is that it may provide better control of the seizure onset patterns and seizure spread, thereby improving both the tolerability and efficacy of seizure treatment. Like ECT, MST is performed under general anesthesia in a medical suite. Clinical trials and several case reports have already indicated that MST may cause less cognitive impairment than ECT, though it is not yet clear if it will be as effective as ECT (Lisanby et al., Neuropsychopharmacology, 2003; 28:1852-1865).

In cortical stimulation, electrodes are implanted on top of the brain’s cortex; these electrodes are then connected with a wire to a neurostimulator implanted subcutaneously in the patient’s chest (www.northstarneuro.com). The amount and frequency of the stimulation can be controlled by the clinician using a handheld device. A recent multicenter randomized controlled trial for improving the recovery from stroke demonstrated the treatment is safe, but failed to show efficacy (http://www.forbes.com/markets/feeds/afx/2008/01/22/afx4557007.html). The company is now focusing on using the device to treat depression. In October, the FDA granted conditional approval for a feasibility trial evaluating cortical stimulation for the treatment of treatment resistant major depressive disorder.