Could Genes Determine Whether Anti-Depressants Make Us Suicidal?

In an article published today in the American Journal of Psychiatry, Gonzalor Laje, M.D. and his colleagues at the National Institutes of Health, University of Texas, and Mount Sinai School of Medicine, report findings that there may be two genetic markers that increase the likelihood of suicidal thoughts during the course of antidepressant treatment. Their motivation for the study was in part guided by the life-threatening nature of suicidal thoughts during the course of antidepressant treatment with SSRIs, or selective serotonin reuptake inhibitors, despite being a relatively rare occurrence. The researchers hope to add to the growing body of knowledge that may one day enable clinicians to identify patients who would be at an increased risk for developing suicidal thoughts during the course of antidepressant treatment through a routine genetic screening process. In turn, it may enable clinicians to determine the best drug for each patient during the course of anti-depressant treatment. "If we have genetic markers or blood tests that would tell us who is at a higher risk of developing suicidal thoughts when they take an antidepressant, we can provide them a different type of treatment, give them a different follow-up, or in the case of primary care physicians or pediatricians in the community treating patients, they can refer them to a psychiatrist," says Laje.

Implementing a standard study protocol at 18 primary care and 23 psychiatric care settings across the United States, the researchers collected participants between the ages of 18 and 75 years for their study. Participants met the DSM-IV criteria for nonpsychotic major depressive disorder, which is the standard criteria clinicians use for diagnosing depression. The patients also had initial scores of greater than or equal to 14 on the 17-item Hamilton Depression Rating Scale, commonly used for diagnosing depression; such scores clearly demonstrate a strong depressive symptomatology.

Dr. Laje and his colleagues gave the participants the anti-depressant drug known as Citalopram, starting at a dose of 20 mg/ day, and increased the dose as needed according to previously recommended procedures. Additionally, Dr. Laje collected DNA samples from all of the participants. Ultimately, after several rigorous exclusion procedures of participants, he and his colleagues collected data from 120 patients experiencing suicidal thoughts as a result of Citalopram treatment.

Furthermore, the researchers included a comparison group of 1,742 people in the study. The participants in this group either denied having any suicidal thoughts at initial and subsequent visits or acknowledged having suicidal ideas at the initial visit before the start of treatment. In either case, the researchers excluded the possibility that Citalopram could be causing suicidal thoughts in these control patients. Thus, though these patients were given the same dosages of Citalopram as the other 120 patients, they did not have the same or increased emergence of suicidal thoughts in response to Citalopram treatment.

Dr. Laje and colleagues compared the DNA of the 1,742 participants in the nonsuicidal group to the 120 other patients to see what was different in the 120 patients that made them more susceptible to suicidal ideation during anti-depressant treatment. They found that two genetic markers were significantly correlated with suicidal ideations after treatment with Citalopram. These genetic markers were found in two genes that code for receptors for glutamate, an excitatory neurotransmitter found in the brain. The implications of this finding are still unclear, but suggest a role for glutamate in suicidal ideation during anti-depressant treatment.

The researchers are cautious about the extent of their findings. As the study only tested Citalopram, the findings apply to this drug only. The researchers have yet to determine the presence of a correlation between the genetic markers they have identified in this study and suicidal ideations when the subjects are treated with other drugs.

Written by: Shilpa Gowda

Reviewed by: Hoi See Tsao and Dean Corbaley

Published by: Konrad Sawicki

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