Experimental new approach for treatment-resistant depression
A recent paper in the Archives of General Psychiatry, a leading psychiatric journal, describes a study investigating deep brain stimulation (DBS) for the treatment of depression. This study involved electrical stimulation of a specific brain region via surgically implanted electrodes in 17 persons suffering from severe treatment-resistant depression. Participants were evaluated for a period of two years after the surgery. DBS involving a different brain location has been used successfully for many years to help patients with Parkinson’s disease.
Eugene Rubin, M.D., Ph.D., is Professor and Vice-Chair for Education in the Department of Psychiatry at Washington University in St. Louis – School of Medicine. He is also Professor of Psychology at Washington University in St. Louis. He is a clinical investigator in the Washington University Alzheimer’s DiseaseResearch Center, and he is involved in clinical research studying depression in the context of co-morbid medical illness. He was the director of the psychiatry residency training program at Washington University in St. Louis School of Medicine from 1987-2007.
Editor: Muhammad Talha
The 17 patients in this study were all very ill. On average, they were in their 40s and had their first episode of depression around the age of 20. Most had been hospitalized, and all had been treated with a variety of medications and therapies. Many had failed to respond to electroconvulsive therapy (ECT). Almost half had attempted suicide, and the average length of their current depressive episode was over 5 years. Ten of the study participants had never experienced episodes of mania or hypomania and hence suffered from “unipolar” depression. Seven suffered from depression associated with bipolar disorder(i.e., they had experienced prior episodes of hypomania). Most were unable to work because of their depression.
After six months of DBS, seven people demonstrated clinically significant improvement and three improved so dramatically that they were said to be in remission (meaning they had very few or no remaining symptoms). After two years of stimulation, 92 percent had improved substantially and 58 percent were classified as in remission. Notably, patients with bipolar depression, which is often very difficult to treat, responded just as well to the stimulation as those with unipolar depression. No patient developed manic or hypomanic symptoms as a result of DBS.
The original research design included a planned period of time in which the electrical stimulation was discontinued in some of the participants without their knowledge. This was done to determine whether observed effects were truly the result of electrical stimulation. When this part of the research protocol was attempted in three participants, they rapidly relapsed and became severely depressed. This was so dramatic that this part of the protocol was eliminated for ethical reasons. When the stimulation was restarted in these three people, they did respond, but it took months for them to regain the ground they lost.
One important aspect of this study is that it helps validate previous neuroscientific research defining depression-related brain pathways. The specific brain area was chosen for DBS in this project on the basis of prior research utilizing the tools of neuroimaging and neuroanatomy to determine brain circuitry involved in depression. The results of this study are highly encouraging and, to our knowledge, this marks the first treatment in psychiatry to evolve from neuroimaging research. Other research has provided preliminary evidence that stimulating a different brain region can help treat severe obsessive compulsive disorder (OCD). These are direct demonstrations that targeting specific brain areas to treat psychiatric illnesses is both possible and effective. As researchers continue to map brain circuits that are abnormal in specific psychiatric illnesses, less invasive methods of influencing these brain circuits can hopefully be developed. Implanting electrodes into a person’s brain is invasive, expensive, and can have side effects; however, we believe it will only be a matter of time before less invasive approaches to correcting abnormally functioning circuits will be developed.
Once DBS is approved for use in depression, it will be very important that it is used only for people with severe and clearly defined illness. Many patients suffer from forms of depression that are complicated by personality disorders and substance abuse disorders. Until and unless this invasive treatment has been shown to work in patients with these mixed diagnoses, it should be reserved for patients with clearly defined severe unipolar or bipolar depression uncomplicated by other psychiatric disorders.
Deep brain stimulation represents a significant step towards a better understanding of brain pathways and disabling brain disorders. It is important to note, however, that DBS is an experimental tool. We still have a lot to learn about the benefits and risks of this type of treatment before it becomes more widely available.