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Last Updated: Oct 11, 2012 - 10:22:56 PM |
Research Article
Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study
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Depression Channel 
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Genetic variations may predispose some men to suicidal thoughts during treatment for depression
Jun 7, 2007 - 4:00:00 PM
, Reviewed by: Dr. Himanshu Tyagi
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Regardless of treatment specificity, nearly all antidepressant medication studies find that some patients experience suicidal thoughts and behaviors after treatment initiation. Identification of this subpopulation before treatment would have tremendous clinical utility.
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Level of Evidence
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3b - Individual Case-Control Study
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Key Points of this article
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If replicated, this finding would suggest that pharmacogenetic testing could facilitate the identification of the small subset of individuals at greater risk during short-term antidepressant treatment
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Main results
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Two of five single nucleotide polymorphisms (SNPs) - variations that occur when a single building block of DNA is altered - were significantly and strongly associated with the onset of suicidality in men, but not in women.
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STAR*D study
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The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study, funded by the NIH National Institute of Mental Health in USA, is a US wide public health clinical trial. The purpose of the trial is to determine the effectiveness of different treatments for people with Major Depressive Disorder (MDD) who have not responded to initial treatment with an antidepressant. This is the largest and longest study ever done to evaluate depression treatment. Over a seven-year period, the study enrolled more than 4,000 outpatients, aged 18-75 years. The participants were people who came to their doctors for care and who had other psychiatric and medical conditions like those regularly seen in typical clinical practices. Patients from both mental health (specialty care) and non-mental health (primary medical care) practices in diverse racial, ethnic, and socioeconomic populations were enrolled in the study. Source: NIMH
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By JAMA and Archives Journals,
[RxPG] Genetic variations may help explain why some men with depression develop suicidal thoughts and behaviors after they begin taking antidepressant medications, while most do not, according to a report in the June issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
Although most patients with depression respond favorably to antidepressant medications, a very small subgroup may experience worse symptoms after beginning treatment, according to background information in the article. "Regardless of treatment specificity, nearly all antidepressant medication studies find that some patients experience suicidality [suicidal thoughts and behaviors] after treatment initiation," the authors write. "Identification of this subpopulation before treatment would have tremendous clinical utility."
Roy H. Perlis, M.D., of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues studied 1,447 individuals with depression who were part of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, which was conducted from July 2001 to September 2006, and who did not express suicidal thoughts at the beginning of the study. The participants were men and women ages 18 to 75 years who had been diagnosed with non-psychotic major depressive disorder. They took the antidepressant citalopram hydrobromide for up to 12 weeks, following a protocol that advised follow-up treatment visits at two, four, six, nine and 12 weeks, with an optional visit at 14 weeks if needed. The patients' DNA was analyzed for common types of mutations nearby or within the CREB1 gene, which codes for a protein previously suggested to be involved in both antidepressant effects and suicide.
Of the 1,447 patients, 123 (8.5 percent) reported suicidal thoughts or behaviors during at least one follow-up visit, including 54 (10 percent) of the 539 men. Two of five single nucleotide polymorphisms (SNPs) - variations that occur when a single building block of DNA is altered - were significantly and strongly associated with the onset of suicidality in men, but not in women.
The researchers performed additional analyses suggesting these variations are not linked to suicidal thoughts and behaviors in men before treatment. "No statistically significant association was noted between any SNP and the presence or absence of baseline suicidality," the authors write. "Likewise, no evidence of association was noted between any SNP and history of lifetime suicide attempt."
Studies that link genes to illnesses are most compelling when there is additional evidence of that gene's function, the authors note. "We recently observed an association between the same CREB1 polymorphisms and a measure of anger expression among males but not females in a sample of 94 patients with major depressive disorder; hostility and anger expression have also been associated with suicide," they write.
"If replicated, this finding would suggest that pharmacogenetic testing could facilitate the identification of the small subset of individuals at greater risk during short-term antidepressant treatment," the authors conclude.
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About Dr. Himanshu Tyagi
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This news story has been reviewed by Dr. Himanshu Tyagi before its publication on RxPG News website. Dr. Himanshu Tyagi, MBBS is the founder editor and manager for RxPG News. In this position he is responsible for content development and overall website and editorial management functions. His areas of special interest are psychological therapies and evidence based journalism.
RxPG News is committed to promotion and implementation of Evidence Based Medical Journalism in all channels of mass media including internet.
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Additional information about the news article
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STAR*D has a unique study design that mimics clinical practice and ensures high levels of patient participation, making the results directly applicable to practitioners and their patients. This study was conducted by psychiatrists and primary care physicians in both private practice and public clinics to reflect the treatments patients typically receive in community settings. The study reflects what is done in clinical practice by allowing the study participants to choose what treatments would be acceptable to them, and then limiting randomization of each participant only to his/her range of acceptable treatment strategies. No prior studies have evaluated the acceptability of different treatment strategies in broadly defined participant groups treated in diverse care settings.
STAR*D aimed for the first time to provide solid scientific evidence regarding which next treatment steps are best for treatment-resistant depression. The results should produce clinical, administrative and economic benefits.
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