Posted by SLS on September 19, 2009, at 9:55:45
http://www.medscape.com/viewarticle/709155?src=mpnews&spon=12&uac=41170BN
Biomarker Predicts Response to Antidepressant TreatmentSeptember 17, 2009 Two new related reports provide further evidence of the usefulness of neurophysiological biomarkers in determining the effectiveness of antidepressant medication.
The first report from the Biomarkers for Rapid Identification of Treatment Effectiveness in Major Depression (BRITE-MD) study confirms that a biomarker of changes in prefrontal brain activity used 1 week after initiation of treatment with the selective serotonin reuptake inhibitor escitalopram (Lexapro, Forest Pharmaceuticals, Inc) can predict response and remission rates 7 weeks later.
The second report found that patients who were predicted not to respond to escitalopram after 1 week and were switched to bupropion XL (Wellbutrin XL, GlaxoSmithKline) were almost 2 times more likely to respond to the new drug as those who remained on escitalopram.
These findings suggest that the biomarker, used early in treatment, may help identify not only whether a patient is likely to respond to treatment with a selective serotonin reuptake inhibitor but also whether a patient is likely to respond if switched to a different antidepressant early in treatment.
The studies are published in the September issue of Psychiatry Research.
New Hope
This research could give new hope to patients who sometimes wait for months for relief from depressive symptoms, said lead author of the studies Andrew Leuchter, MD, professor of psychiatry, Semel Institute for Neuroscience and Human Behavior, University of CaliforniaLos Angeles. "This approach could really change the way we care for depression, get people back on their feet more quickly, and save healthcare costs," he said in an interview.
The BRITE-MD study included 375 patients aged 18 to 75 years from 9 sites across the United States. All subjects met Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for major depressive disorder based on the Mini International Neuropsychiatric Interview and had a Quick Inventory of Depressive SymptomatologySelf Rated Version score of 12 or more. At baseline, severity of illness was assessed using the Inventory of Depressive SymptomatologyClinician Rated scale.
Researchers used quantitative electroencephalography, a noninvasive, computerized measurement of alterations in brain-wave activity alterations that may precede improvement in mood by several weeks. This involved applying electrodes to subjects at 4 sites on the forehead and 2 on the earlobes. The researchers recorded the data while the subjects rested in a reclining chair during 2 6-minute periods.
The patients were examined with quantitative electroencephalography again after 1 week of treatment with 10 mg daily of escitalopram.
Researchers used the Antidepressant Treatment Response (ATR) index, a biomarker that predicts treatment response based on changes in brain-wave patterns from the baseline quantitative electroencephalography.
The ATR scale ranges from 0 to 100, with lower numbers indicating a lesser likelihood of response to medication and higher numbers indicating a greater probability of response.
For this study, researchers used a cutoff or threshold of 58.6, above which a measurement was considered a "positive" biomarker and below which it was a "negative" biomarker.
The subjects were then randomly assigned to either continue on 10 mg of escitalopram or change to bupropion 300 mg, or to receive a combination of escitalopram 10 mg with bupropion 300 mg.
Researchers also collected serum drug levels and genotyping data.
First Results
Researchers were able to evaluate 220 of the 375 participants who completed the study, including 73 who continued on escitalopram for 49 days. The first study reported results in this group.
In these 73 patients, the response rate (defined as a decrease in the Hamilton Depression scale of at least 50% from baseline) was 52.1% and the remission rate (a Hamilton Depression scale score of 7 or less) was 38.4%.
Responders and remitters had significantly higher ATR values than those who did not. The ATR predicted both response remission with a 74% overall accuracy.
"At 1 week, we could predict what was going to happen at 7 weeks with 74% accuracy," said Dr. Leuchter.
Neither serum drug levels nor common genetic polymorphisms in the seratonergic system were significantly associated with response to escitalopram.
Companion Study
A companion study reported on all the subjects who completed the study. It found that response rates for the escitalopram, bupropion, and combination therapy groups were 52.1%, 41.1%, and 39.2%, respectively. Remission rates were 38.4%, 26%, and 32.4%, respectively.
This second study found that negative biomarker subjects who switched to bupropion were 1.9 times more likely to respond to this new drug and had a greater remission rate, although the latter failed to achieve statistical significance.
"We knew from our prior work that a positive ATR was a very strong indicator of response, and we proved that again in the first study, but the question was, if you have a negative ATR, does that mean you're not going to get well on anything, or does it mean that you need a different drug?" said Dr. Leuchter.
"The second study suggests that if you give people a totally different drug, in this case bupropion, which has a completely different mechanism of action, they're very likely to get well on that," he added.
Better Than 'Trial And Error' Approach
Using biomarkers to determine treatment response has a number of advantages over the current "trial and error" approach, said Dr. Leuchter. "Right now, by the time you've waited 7 weeks to find that somebody's not going to respond, and then you switch to another drug, that patient is disabled for a long period of time, he or she is suffering, and their families are suffering, and it's costing them a lot of money."
The biomarker approach should also improve medication adherence. As it stands, most people stop taking a medication within 4 weeks well before it can be determined whether or not it will work. "Patients get discouraged, they give up, they have side effects, and they don't know if they're going to get better," said Dr. Leuchter.
The biomarker test is noninvasive, painless, and takes less than 15 minutes to complete, he added.
Although still considered experimental, Dr. Leuchter hopes the biomarker test will get regulatory approval within a few years.
Important, Intriguing, Exciting
Asked to comment on the findings, James B. Potash, MD, MPH, associate professor, psychiatry, Arlene and Robert Kogod Professorship in Mood Disorders, and research director, Mood Disorders Center, Baltimore, Maryland, said the biomarker concept is "important, intriguing, and exciting" and could be "incredibly useful" for physicians in determining in advance which medications will work.
However, he pointed out that this research was sponsored by, and to a substantial degree conducted by, the company (Aspect Medical Systems) that manufactures the electrodes used in the study.
"The heavy involvement of the company that makes the electrodes raises the question of whether the desired level of academic objectivity was met," he said.
He also pointed out that the ATR index was derived from a relatively complex composite, and its creation may have involved a fair amount of "mixing and matching and mathematically manipulating of [electroencephalogram] parameters" to arrive at a marker that correlated with antidepressant response.
"That's not a bad thing; it just means that in terms of one's level of confidence, you can't be sure that this isn't a chance finding, and you'd like to see replication."
poster:SLS
thread:917672
URL: http://www.dr-bob.org/babble/wdrawl/20090801/msgs/917672.html