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Deep-Brain Stimulation Shows Promise for Treatment-Resistant Depression Marlene Busko July 30, 2008 - In an early study, 6 months after 20 patients with treatment-resistant depression underwent deep-brain-stimulation surgery, 60% had responded to treatment and 35% had attained remission. These results were largely sustained out to 1 year, and the procedure was well tolerated. These findings, by Andres M. Lozano, MD, a neurosurgeon at Toronto Western Hospital, in Ontario, and colleagues, extend the group's earlier observations of 6 patients (Neuron 2005;45:651-660). The current study was published online in the July 21 issue of Biological Psychiatry. "Impressive," Sustained Results "I think the fact that we've gone out to 1 year and shown the sustained effect of this treatment has been quite impressive," coauthor Sidney H. Kennedy, MD, psychiatrist-in-chief at the University Health Network, in Toronto, told Medscape Psychiatry. "It's not a depression-free future, but when people have had symptoms, they've been less severe and less prolonged," he said. According to Dr. Kennedy, the subcallosal cingulate gyrus (area 25) that was stimulated is pivotal in many people with treatment-resistant depression, but the brain region that needs to be treated is not the same in everyone. The deep-brain-stimulation system consists of a neurostimulator that is surgically implanted near the collarbone and is connected to implanted leads and extension wires in the brain. The system has an external controller and programmer. "You don't just stick the stimulator in with the battery under [the patient's] clavicle in [their] chest and say, 'goodbye and good luck'." said Dr. Kennedy. "It might be seen as an enabling aspect of [depression] treatment, so that people are then able to work with their psychiatrist...usually with medication, but at lower doses than was required before...and sometimes combined with cognitive therapy." More Than 4 Unsuccessful Treatments Approximately 10% to 20% of patients with depression continue to be severely disabled, despite adequate trials of antidepressant drugs, psychotherapy, and electroconvulsant therapy, the authors write. Functional imaging studies have shown that depression is linked to increased activity in the subcallosal cingulate gyrus, they add. In 2006, it was estimated that 30,000 to 40,000 people worldwide with Parkinson's disease underwent deep-brain-stimulation surgery, as did between 30 and 50 people with treatment-resistant depression, said Dr. Kennedy. The surgery has now been used to treat probably close to 100 people with treatment-resistant depression, he noted. In the initial study, the group implanted deep-brain-stimulation electrodes in the subcallosal gyrus of 6 patients with treatment-resistant depression. Four of these had a remarkable response and have continued to function well over the subsequent 5 years, said Dr. Kennedy. The current study reports clinical effects, safety, and changes in brain activity in these 6 patients and an additional 14 patients who were followed for 12 months. Between May 2003 and November 2006, the researchers performed deep-brain stimulation on 9 men and 11 women. The subjects had a minimum score of 20 on the 17-item Hamilton Rating Scale for Depression (HRSD-17) and had failed to respond to at least 4 different treatments for depression, including antidepressant drugs, psychotherapy, and, except for 3 patients who refused, electroconvulsant therapy. After surgery, the investigators performed regular psychiatric assessments and, if needed, stimulator adjustments. The primary outcome was the percentage of patients who achieved a response, which was defined as a 50% or greater reduction in depression severity (as measured by HRSD-17 scores). The secondary outcome was the percentage of patients who achieved clinical remission, which was defined as a HRSD-17 score of 7 or less. The researchers also examined changes in the mood, anxiety, somatic, and sleep subcomponents of the HRSD-17. Positron emission tomography (PET) scans were performed to measure regional glucose metabolism and determine changes in brain activity. May "Rebuild Lives," Needs Further Study The patients showed early progressive benefits from surgery that plateaued at 6 months. At 1 month after surgery, 35% of patients responded to treatment and 10% attained remission. At 6 months after surgery, 60% of patients had responded and 35% achieved remission - benefits that were largely maintained at 12 months. The number of serious adverse effects was small and included wound infection (4 patients), headache (4 patients), irritability (2 patients), and seizure (1 patient). No patients experienced permanent deficits. "Overall, patients were markedly improved with surgery and the benefits were sustained over time, leading in certain cases to reintegration into their family and social activities and a return to past work activities," the authors write. PET scans revealed that areas that were to some extent dampened in the depressed state improved in people as the depression lifted, said Dr. Kennedy. As the patients started to rebuild their lives, they were better able to use cognitive therapy; before surgery, they were too fatigued and unmotivated and had memory problems, he added. Providing deep-brain stimulation for treatment-resistant depressed patients requires a dedicated multidisciplinary team of neurosurgeons, psychiatrists, and support staff, the researchers write. "While these results, particularly in this difficult-to-treat population, are promising, they represent an initial step, and a blinded evaluation of deep-brain stimulation in treatment-resistant depression is required before it can be adopted on a wider scale," they conclude. This work was supported in part by a Distinguished Investigator Award from National Alliance for Research on Schizophrenia and Depression (NARSAD). Dr. Lozano is a consultant for Advanced Neuromodulation Systems and Medtronic and holds intellectual property and licenses in the field of deep-brain stimulation. Dr. Kennedy has been a member of the speaker's bureau and received honoraria from Biovail, Eli Lilly, GlaxoSmithKline, Janssen-Ortho, Lundbeck, Organon, Servier, and Wyeth; he has received consultant fees from Advanced Neuromodulation Systems Inc., Biovail, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen-Ortho, Lundbeck, Organon, Pfizer, Servier, and Wyeth; and he has received grant funding from AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen Ortho, Lundbeck, and Merck Frosst. Coauthor Helen Mayberg, MD, from the University of Toronto, is a consultant and has obtained licensing fees from intellectual property from Advanced Neuromodulation Systems. Biol Psychiatry. Published online before print July 21, 2008. Rayilyn Brown Director AZNPF Arizona Chapter National Parkinson Foundation [log in to unmask] ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn