CHICAGO, April 28 -- Investigational deep-brain stimulation gave year-long relief from severe depression in half of patients in a small study who had been refractory to multiple conventional therapies, a researcher said here.
Eight of 16 patients showed at least 50% improvement in depression scores, reported Ali R. Rezai, M.D., of the Cleveland Clinic in an interview before his presentation at the American Association of Neurological Surgeons meeting here.
"[Responders] had significant improvement in quality of life, returning back to work, getting engaged, dating," Dr. Rezai said.
- Explain that deep-brain stimulation involves delivering electric pulses to specific points in the brain from an implanted pacemaker-like device. It is currently used to treat Parkinson's disease and other movement disorders.
- Explain that deep-brain stimulation for depression is investigational and has not been approved by the FDA.
- Point out that the study was not controlled or blinded and involved only 16 patients.
- Point out that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.
He noted that about 15% of all patients with major depression fail to respond to drugs, behavioral interventions, or electroconvulsive therapy.
The study enrolled 17 patients overall, with one patient not yet completing a year of treatment when the data were analyzed.
Patients had severe and disabling major depression lasting at least five years without response to at least three classes of antidepressants titrated to the highest tolerated doses. All patients also failed combined therapy with at least two augmentation agents and multiple electroconvulsive therapy trials.
Those considered to be at imminent risk of suicide were excluded, as were patients with current or past psychotic disorders, associated neurological disorder, any significant brain imaging abnormality, substance abuse, history of severe personality disorder, coagulopathy, or other medical problems that could increase the risk of surgery.
Treatment involved placement of a Medtronic Soletra implantable pulse generator, a pacemaker-like device used in deep brain stimulation for Parkinson's disease. Bilateral leads were placed in the ventral portion of the anterior limb of the internal capsule and ventral striatum with high-resolution MRI targeting.
Each electrode contact was 3 mm long with 4 mm of spacing or insulation between contacts. The diameter and other physical properties were the same as the common electrodes used in deep brain stimulation for movement disorders, Dr. Rezai said.
Outcome measures included scores on the Montgomery-Asberg Depression Rating Scale and the Global Assessment of Functioning. The assessments were performed by a nurse who was blinded to the treatment parameters. Patients were also evaluated for IQ, visuomotor speed, mental flexibility, verbal and visual memory, and conceptual reasoning.
Mean Montgomery-Asberg score at baseline was 34.7 (SD 6.9).
Dr. Rezai reported a mean decline of 52.3% in Montgomery-Asberg scores among the 16 patients who completed one year of treatment.
The formal clinical response criterion in this study was a decrease in the Montgomery-Asberg Depression Rating Scale score of at least 50% compared to baseline. The criterion was met by eight of 17 patients (47.1%) at the six- month follow-up and by eight of the 16 patients (50%) at 12 months.
Treatment benefits were apparent after the first three months, as the mean decline in Montgomery-Asberg scores was 52.7% at that evaluation.
Mean Global Assessment of Functioning scores rose from 42.5 at baseline to 61.5 after one year (SD not provided). Most of the benefit was achieved by month three.
Neuropsychological assessments showed no significant deleterious effects associated with chronic stimulation, Dr. Rezai said. Improvements in short-term memory were also seen.
There were no major adverse effects such as hemorrhage or infection, he said. One patient reported discomfort from the leads, which resolved after they were relocated.
Two patients had a return of depressive symptoms and suicidal ideation when their pulse generators were accidentally turned off. Restarting them again led to symptom improvement, Dr. Rezai said.
The pulse generators can stop working when exposed to strong magnetic fields, such as in metal detectors, or when the batteries run out, he explained.
He said the next step would be a randomized, controlled trial.
He said Medtronic is currently sponsoring a double-blind, cross-over trial. All patients will have the devices implanted, but half the patients will not have the units switched on immediately so that they can serve as controls.
Dr. Rezai also reported favorable results at the neurological surgeons' meeting here with deep-brain stimulation in patients with treatment-refractory obsessive-compulsive disorder. Following up on the new findings, the Department of Health and Human Services and the Cleveland Clinic announced a one-day conference to be held May 6 in Washington focusing on deep-brain stimulation. It will include discussion of the impact of deep-brain stimulation on patients' quality of life, level of functioning, and ability to work. The agenda will also cover access to care and ethical considerations, according to a joint statement from HHS and Cleveland Clinic.