Physician's Weekly Article - DBS: New Hope for Intractable Major Depression?

       Historically, patients with intractable major depression have had little hope for recovery, but new research indicates that deep brain stimulation, or DBS, may be a promising remedy for these individuals.

      According to recent estimates, about 9.5% of all Americans—or 18.8 million adults—suffer from a depressive disorder each year, costing as much as $40 billion annually in the U.S. workplace. Although many patients with major depression will have their condition relieved via psychotherapy, medications, electroconvulsive therapy (ECT), or a combination of these modalities, some patients will still not experience improvements with these interventions. “Considering the magnitude of intractable major depression, clinicians and researchers are seeking out new means for treating patients with the most severe depression so that they too can achieve benefits,” says Donald A. Malone Jr., MD.

      A Look Into DBS

      Deep brain stimulation (DBS) has been used to treat intractable pain for several decades. More recently, the technology has received expanded indications from the FDA to treat patients with Parkinson’s disease and other movement disorders. DBS is also being investigated for the treatment of epilepsy, obsessive-compulsive disorder (OCD), and other debilitating neurological conditions. These procedures involve surgical placement of tiny implantable electrodes into specific parts of the brain that function abnormally (Table 1). Tiny pulses of electrical stimulation are emitted to block the abnormal brain activity.

      “Key advantages of DVS are that it is reversible, it is nondestructive, and it can be modified by adjusting the stimulator settings after implantation,” explains Dr. Malone. “Although DBS appears to be a significant advance for many neurological conditions, there are risks associated with it—as with any surgery—and it might not be effective for all patients.” Success of DBS depends on the surgical team’s ability to precisely pinpoint the specific brain area for stimulation.

      Exciting New Data

      Vagus nerve stimulation (VNS) is the only surgical intervention currently approved by the FDA for treatment-resistant depression, but this procedure is often not covered by insurance. Even when VNS is administered, only some patients—not the majority—will benefit. The search for an alternative has continued, and DBS is now being explored to treat these patients. “Since 2001, together with colleagues from Brown University and the University of Florida, we have been using DBS for OCD,” says Dr. Malone. “We’ve found that this strategy improved anxiety and obsessions and also led to improvements in comorbid depression. As such, our research team initiated a new study to analyze the effects of DBS on patients with major depression.”

      At the 2008 annual meeting of the American Association of Neurological Surgeons (AANS), Dr. Malone and colleagues from institutions throughout the United States presented preliminary results from a multi-center open-label trial assessing the use of DBS for the treatment of intractable major depression (Table 2). “The study involved 15 patients with chronic depression who underwent DBS,” Dr. Malone says. “About half of these individuals achieved a 50% or greater response to DBS when measured at 6 months, and no one in our study group had their depression worsen after implantation. Furthermore, there were substantially rapid declines in suicidality among these patients. Perhaps most importantly, six of the 15 patients were in complete remission when last assessed. Considering the severity of illness for these patients, having a third of the participants achieve remission is astounding.”

      More Studies Needed

      Although the results from the study presented at AANS meeting were encouraging, Dr. Malone warns that more research is necessary before DBS will be used more broadly for patients with intractable major depression. “Our study sample was small, and we still need to establish which depressed patients are ideal candidates for DBS,” he says. “In this preliminary evaluation, patients had previously failed a mean of six different trials of antidepressants, six additional trials of combination or augmentation treatments, and at least one course of bilateral ECT, and most had years of psychotherapy. Long-term and larger trials are needed to evaluate the safety and efficacy of DBS for depression. We may find that ideal depressed candidates for DBS may be less ill, but we need more studies before we can determine appropriate patient selection.”

      Despite the need for more data, Dr. Malone says his study group’s findings could have a significant impact on patients with intractable major depression. “Patients in our study tolerated DBS remarkably well, especially considering the fact that it’s a surgical intervention. All patients have continued to get their DBS batteries replaced because they feel better on treatment than they did before getting it. They may not be true ‘responders’ and achieve symptom improvements of 50% or better, but they are feeling better. If patients believe that the surgery is worth it, even for small changes, then DBS could represent a significant breakthrough for this hard-to-treat patient group.”

      Donald A. Malone, MD, Jr., has indicated to Physician’s Weekly that he has worked as a consultant for Medtronic and a paid speaker for Eli Lilly and Bristol-Myers Squibb. He has also received grants/research aid from Medtronic and Bristol-Myers Squibb.