The Darker Side of Happy Pills

Variant genes increase suicidal thoughts

By: Jigyasa Jyotika /The Daily Cardinal

New study begins to unravel the dark side of antidepressants

Although most people are knowledgeable about the positive effects of antidepressants (a.k.a. “happy pills”), far fewer are aware of the dark side of these drugs—the same pills prescribed to help make patients happy may be leading some patients to suicide.

Researchers and doctors became increasingly alarmed during 2004 when studies suggested antidepressants increased the risk of suicide in some adolescents and children. As a result of these studies, the Food and Drug Administration required all antidepressant medications to carry “black box warnings,” alerting parents and patients of the risks associated with taking antidepressants.

While scientists have continued to struggle to make sense of the paradoxical relationship between the use of antidepressants and increased rates of suicide since 2004, this October, researchers at the National Institutes of Mental Health discovered two genes that may help to explain this link.

In one of the largest and most comprehensive studies of its kind to date, researchers at NIMH found that the inheritance of one or two genes increased the likelihood of suicidal thoughts among patients taking an antidepressant called citalopram between two- to 15- times compared to those who did not share similar genes.

“This study is a step forward in individualizing depression treatment for patients identified as high-risk for suicides,” said Michael Peterson, a UW-Madison instructor of psychiatry.
Citalopram, a drug within the selective serotonin re-uptake inhibitor family, works to decrease feelings of depression by preventing the recycling of the “happy hormone” serotonin, which results in higher serotonin levels in the brain. According to Peterson, SSRIs are the most commonly prescribed antidepressants.

Scientists from the NIMH looked at 68 suspect genes in more than 1,900 adults with major depression who were treated with citalopram. Based upon patient reports of suicidal thoughts and genetic code variation among the 68 suspected genes, the researchers narrowed their search to two variable gene sequences, or “markers.”

“A small variation in the sequence of these genes is what seems to predispose some people more than others to suicidal thoughts while taking the drug,” said Gonzalo Laje, a co-author of the study.

While participants with only one of two genetic variants were two- to eight-times as likely as those without variants to develop suicidal thoughts while taking citalopram, a NIMH press release reported those with both variants—an extremely rare phenomenon—were 15 times as likely to report suicidal thoughts.

Researchers also found gene variants were not related to self-reported history of suicide attempts, suggesting the genetic variations leading to suicidal thoughts were occurring during antidepressant treatment, not outside treatment.

Overall, 59 percent of the patients who had suicidal thoughts had at least one of the variable gene versions. This still left out 41 percent of the participants, who developed suicidal thoughts without either variant, indicating that other genes and environmental factors may also be involved.

In the future, the NIMH plans to begin to attempt to understand why the identified genetic variations are leading to increased suicidal thoughts among people who take citalopram and if similar variations could be linked to increased suicidal thoughts among people on other antidepressants.

“It remains unclear at this point why we see what we see,” Laje said.