Researchers look at antidepressants and risk of suicide among kids

Which is more likely to push a depressed child to suicide: not taking antidepressant drugs or taking antidepressant drugs?

Medical experts have struggled with this question at least since 1990 when Harvard researchers reported that six people developed suicidal feelings soon after taking Prozac (fluoxetine). This was the first of the now widely prescribed serotonin drugs to ease depression. Called selective serotonin reuptake inhibitors, or SSRIs, such medications ease the problems of depression, anxiety, and obsessive-compulsive behavior by decreasing the activity of a brain chemical known to affect moods.

Despite the 1990 reports, doctors had, by 2002, begun prescribing these drugs for children and adolescents. “The Food and Drug Administration had not granted specific approval for this, but ‘off-label’ prescribing is a common and accepted practice,” notes an article in the July issue of the Harvard Mental Health Letter. In 2003, the FDA went ahead and approved Prozac for treating depression in people 18 years and younger.

Since then, a variety of SSRIs have been cleared for treating major depression, anxiety, and obsessive-compulsive disorder for adults. However, since 2003, reports of young users committing or attempting suicide had become too numerous to ignore.

The following year, the FDA reported the results of 24 tests involving 11 antidepressants and almost 4,500 children and adolescents. The agency concluded that the drugs involved a doubling of the risk for suicidal behavior. Four percent of young people taking antidepressants, compared with 2 percent of those taking dummy pills, “were found to have definitely or possibly thought about killing themselves or taken actions that might have led to suicide,” according to the Harvard review.

The happy ending to this story is that no one in any of the studies actually committed suicide.

Black-box warnings

By 2004, the FDA ordered so called black-box warnings — the most serious alerts — added to all labels on antidepressant medications. The warning clearly states that antidepressants raise the risk of suicidal thoughts and behavior in children and adolescents.

That action did not end the controversy. In 2005, the American Medical Association adopted a resolution saying that antidepressants had not been proven to raise the number of completed suicides in people 18 years and younger, and that children “should not be denied possibly life-saving medication on the basis of equivocal evidence.”

With the ball back in its court, the FDA asked drugmakers to provide information from medical trials of suicidal behavior and thinking among adults treated with antidepressants. The results, which involved more than 100,000 adults, were announced in 2006. The data revealed a slightly higher risk for suicidal thinking and behavior in people up to age 25. No differences were found at ages 25 to 30. A slightly decreased risk was found for those 30 years and older, and that risk declined further after age 65.

By May of this year, FDA advisers recommended adding a postscript to the black-box warning, calling attention to the protective effect of antidepressants for older people and to the suicide risk of untreated mental illness.

About the same time, an analysis of more than 5,000 patients age 19 and younger concluded that antidepressants can be effective for treating not only major depression but anxieties and obsessive-compulsive disorders. Results were greatest for anxiety and smallest for depression. The researchers, from the Western Psychiatric Institute and Clinic in Pittsburgh, estimated that an antidepressant would be helpful for one out of every three young patients treated for anxiety, one of every six for obsessive-compulsive behavior, and one of every 10, or 10 percent, of youngsters with major depression. These results appeared in the April 18 issue of the Journal of the American Medical Association.

This analysis also found an age difference. Most of the drugs helped only adolescents, those more than 12 years old. Prozac, alone, was effective for those 12 years and younger. At present, Prozac is the sole drug approved by the FDA for treating depressed children.

Another study, reported last year in the Archives of General Psychiatry, also found an age difference. Each of 263 patients hospitalized for depression who attempted or committed suicide was matched with hospitalized depressed patients who were not suicidal. Use of antidepressants was not more common among those 19 and older who became suicidal than among those who did not. But of patients 18 years and younger who attempted suicide, 46 percent had taken antidepressants compared with 36 percent who did not.

Three of eight young people who died by suicide had taken antidepressants. However, patients who attempted or completed suicides were not more likely to have taken SSRIs, except for Zoloft. Rather, they were more likely to be taking the newer antidepressant Effexor (venlafaxine) or one of the older drugs known as tricyclic antidepressants.

Decreasing the risk

Some people argue that any risk of suicide cannot possibly justify treating children with antidepressants. But the authors of the Western Psychiatric Institute and Clinic report conclude, “The strength of the evidence presented here supports the cautious and well-monitored use of antidepressants….”

The Harvard Mental Health Letter agrees. The best way to get the benefit while decreasing the risk, it says, is careful monitoring and regular follow-up by a doctor. Parents should contact the doctor, the article warns, if a child shows a noticeable shift in behavior: “Examples are a change in appetite, sleep, or energy, becoming anxious, irritable, hostile, or socially withdrawn, or revealing uncharacteristic thoughts or preoccupations. The danger is greatest in the first few weeks after starting a new medication or changing the dose.”

Mental disorders like depression and anxiety are serious risk factors for suicide. “So, for many adults and children, antidepressants can make a vital contribution to reducing suicide risk,” the Harvard review article concludes. Not taking advantage of the benefits of antidepressants may ultimately put children and adolescents at a higher risk for suicide.