Posted by Phillipa on May 28, 2009, at 20:25:09
Thought some might be interested. Phillipa
APA 2009: New Data Suggest Benefit of Deep Brain Stimulation for Refractory Depression
Susan Jeffrey
Read more May 27, 2009 (San Francisco, California) Although the numbers are still small, 2 studies presented here suggest that patients with highly refractory depression may respond to treatment using deep brain stimulation (DBS), although in slightly different parts of the brain, with some achieving remission.Peter Giacobbe, MD, from the department of psychiatry at the University Health Network, in Toronto, Ontario, reported results with DBS of the subgenual cingulated gyrus in 21 patients treated at 3 Canadian centers.
"Using a definition of a 40% decrease in the Hamilton Depression Scale, 62% of people had achieved response at 6 months," Dr. Giacobbe told Medscape Neurology & Neurosurgery. "Of those who had achieved a response by 6 months, 92% were still responders at 12 months, so those who responded early tended to maintain their response."
In a separate study, Donald Malone, MD, from the Cleveland Clinic, in Ohio, reported results in 17 subjects with refractory depression treated with DBS of the ventral capsule/ventral striatum. "We found that on average, at last follow-up, we had 70% response rates and 35% remission, so a third of them are in remission, which you don't typically see with this kind of refractory patient," he said in an interview.
The studies, supported by St. Jude Medical and Medtronic, respectively, were presented here at the American Psychiatric Association 162nd Annual Meeting.
DBS Studies
DBS, already used successfully to treat Parkinson's disease, was first undertaken for refractory depression in Toronto in 2003, when Helen Mayberg, MD, now at Emory University School of Medicine, in Atlanta, Georgia, was at their institution, Dr. Giacobbe said. The initial series of 6 patients was eventually expanded to 20, and results from that series were published last fall, suggesting response rates of about 60%, with about a third achieving remission (Lozano A et al. Biol Psychiatry 2008;64:461-467.)
At this meeting, they report on 21 patients enrolled from their own center, as well as from McGill University and the University of British Columbia, to see whether the initial findings could be replicated in other settings, Dr. Giacobbe said.
Patients included all had major depressive disorder with documented resistance to at least 4 depression treatments, including cognitive behavioral therapy. Of them, 90% had failed electroconvulsive therapy (ECT) he noted, "so this was a highly refractory group of people." All had unipolar depression only; those with bipolar or psychotic depression were excluded. Baseline medications were maintained through the trial.
Response was defined as a 40% decrease on the Hamilton Depression Rating (HAM-D) scale. Using this definition, they found that at 6 months, 62% met the criteria for response; 19% had a partial response, defined as an improvement of 20% to 40% on the HAM-D; and 19% were nonresponders.
At last observation, 92% of the responders were still responding, but half of those who had previously been nonresponders converted to become responders, as did 25% of those who had been partial responders at 6 months. "That suggests that the benefit accrues over time," Dr. Giacobbe said.
At the last follow-up, 2 patients of the 21 had achieved remission of their depression.
In all of the patients, the greatest improvements were seen in core depressive symptoms such as mood, guilt, and motor retardation and in sleep parameters, he noted, with little improvement seen in somatic symptoms such as low energy or low libido. "If you have a patient with more of the core depressive symptoms, they might preferentially benefit from this type of intervention," he said.
Adverse events were similar to those that have previously been seen with DBS, the researchers note. Two serious adverse events were related to a broken extension; the majority of events were mild, with headache being the most common.
There were no changes in any neuropsychological tests, but 3 patients had depression diseaserelated adverse events, including 3 suicide attempts and 1 suicide. "One attempt came from a return of symptoms due to loss of therapy, and all others were judged to be not device-related," the authors note.
Different Stimulation Targets
In a separate report, 17 patients with refractory depression were enrolled from the Cleveland Clinic, Massachusetts General Hospital, and Butler Hospital/Brown University. On average, patients had been depressed for 20 years or more, had failed at least 6 antidepressant trials and another 6 trials of augmentation/combination agents, Dr. Malone said. All 17 had failed ECT, 15 of them in their current depression episode.
In this trial, the target for stimulation was the ventral capsule/ventral striatum, more posterior to the target for stimulation in the Canadian trial.
"There are larger trials going on in both sites as well, so hopefully we'll get more information about which patients may respond to 1 or the other," Dr. Malone noted. However, there is already a precedent for this in DBS for Parkinson's disease, he added. "There's still controversy after it's been approved for 7 or 8 years about whether the subthalamic nucleus or the globus pallidus is the best target, so it's not surprising."
After an average of 37 months of follow-up, response rates, defined as greater than 50% reduction in scores on the Montgomery-Asberg Depression Rating Scale (MADRS), were about 70%, and remission, defined as a MADRS score of less than 10, was seen in 35%.
Table 1. Response (> 50% Reduction on MADRS) End Point 6 mo 12 Mo Last Follow-Up
Responders, n/17 8 9 12
Responders, % 47.1 52.9 70.6
Table 2. Remission (< 10 MADRS Score) End Point 6 mo 12 Mo Last Follow-Up
Remitters, n/17 5 7 6
Remitters, % 29.4 41.2 35.3
Like the Canadian study, response took time in some patients. In these patients, Dr. Malone pointed out, scores of global assessment of functioning were 45 or less, "so they were disabled," he said. "We had 1 lady who basically left her bedroom once a week for 8 years. It's going to take a while to change that behavior."Serious adverse events in this series included hypomania in 1 subject with bipolar depression, syncope of unknown cause, lead fracture requiring revision, pain at the implant site requiring revision, and suicidality/increased depression, the authors note. One subject committed suicide after 5 years of continuous stimulation.
Remission Rates Disappointing?
Asked for some perspective on these findings, Iqbal "Ike" Ahmed, MD, professor of psychiatry at the John A. Burns School of Medicine of the University of Hawaii at Manoa, said that DBS for depression is an area of great interest to the field, "especially since we're dealing more and more with refractory depressed patients. From that standpoint, both of these studies will have a great deal of interest for clinicians as well as researchers."
I think they focus on the positive here which it is but I think they need to address the fact that it's not as robust as one would expect.
The numbers here are still fairly small, and the studies look at different targets for stimulation, although both regions have been implicated in the pathophysiology of depression, Dr. Ahmed noted."On the plus side, there seems to be treatment response, which seems to be sustained," he told Medscape Psychiatry. "On the downside, the numbers who achieve remission are not that impressive, and this is what we are looking for."
In addition, despite the improvement, depression scores remained fairly high, and given the cost and invasive nature of the treatment, he said, "It's a bit disappointing. I think they focus on the positive here which it is but I think they need to address the fact that it's not as robust as one would expect, especially as remission rates go."
Larger trials using sham controls are now under way to address some of these issues. Dr. Ahmed suggested that more data on what separates responders from nonresponders, those who remit and those who do not, would also be helpful.
The studies were funded by Medtronic and St. Jude Medical. Drs. Giacobbe and Malone report that they are consultants for St. Jude Medical and Medtronic, respectively. Dr. Ahmed reports no relevant disclosures.
American Psychiatric Association 162nd Annual Meeting: Abstracts NR3-009, NR6-009. Presented May 19 and May 20, 2009
poster:Phillipa
thread:898165
URL: http://www.dr-bob.org/babble/20090524/msgs/898165.html