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Genes Might Predispose Antidepressant Users to Suicidal Thoughts
Date:9/27/2007

cidal ideation. SSRIs include widely used drugs such as Celexa, Paxil, Prozac and Zoloft.

The black box warning was based on studies that found that 4 percent of the group taking SSRIs had suicidal ideation, compared with 2 percent of the group taking a placebo.

"It is a severe side effect, but it is unusual," Laje stated. "Given the warnings by regulatory agencies, we thought this would be a very important side effect to look at."

The current study was part of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, the largest trial to date to look at depression in real-world settings. Participants in STAR*D were treated with the SSRI citalopram (Celexa) for up to 14 weeks.

For this study, Laje and colleagues analyzed DNA samples from 1,915 participants, looking for associations between reports of suicidal ideation at 768 sites in 68 genes.

Versions of two genes involved with cellular glutamate receptors, which have been implicated in depression, were more prevalent in participants reporting suicidal thinking.

While overall about 6 percent of the patients reported suicidal thoughts when taking Celexa, 36 percent of patients who carried both of the gene variations reported suicidation. Overall, 59 percent of those who reported suicidal ideation had at least one of the suspect gene types.

One percent of the participants had a version of the kainate receptor gene (GRIK2) that increased the risk of suicidal thinking more than eightfold.

Forty-one percent had a version of the AMPA receptor gene (GRIA3) that almost doubled the odds.

Eleven participants, or one-half of one percent, had both versions which resulted in a 15-fold increase in risk.

Since the researchers only looked at Celexa, it's unknown if the findings extend to other antidepressants, even those in the same class of SSRIs.

This study, which is published in the October i
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