Bad Medicine? The data on anti-depressants and child suicide aren’t conclusive. (Expanded Version)

Wall Street Journal, September 10, 2004

By Sally Satel

Do anti-depressants cause suicide in children? After simmering for over a year, the question boiled over this summer. A few weeks ago the makers of Paxil, one of a class of drugs called SSRIs (selective serotonin reuptake inhibitors), agreed to settle with the attorney general of New York who had charged them with “concealing” evidence of harm. Last Thursday, the House Committee on Energy and Commerce held an oversight hearing on the safety of SSRIs. And now the Food and Drug Administration is considering bolstering warning labels on the drugs.

The safety debate was stoked by a long-awaited FDA report. Released mid-August, the report featured an analysis conducted by suicide experts under the auspices of Columbia University. It garnered sensational coverage — “New FDA Analysis Backs Continuing Antidepressant-Suicide Concern,” (Associated Press); “Depression Drugs Could Hurt Youth” (Philadelphia Inquirer); “FDA Ties Some Medicines to Suicide in Kids” (Lexington Herald-Leader) — yet a close look at the 131-page report shows how tenuous these claims are.

The Columbia experts were asked by the FDA to determine whether instances of self-harm that occurred during clinical trials were truly suicide attempts. No child had actually killed himself during the trials — a detail often overlooked in the media coverage — but there were incidents ranging in seriousness from a hanging attempt to lightly scratching one’s arm to a girl who slapped herself in the face.

When the Columbia experts parsed these events into various categories they found relatively little cause for alarm. Within the 15 clinical trials of pediatric depression they examined, youngsters on SSRIs were no more likely to experience an “emergence of suicidality” than those on placebo, nor was there any discrepancy between the two groups with respect to the “worsening of suicidality.”

What the report did find was that youngsters on medications for other conditions (such as anxiety or obsessive-compulsive disorder) as well as for depression were 1.78 times as likely as those on placebo to exhibit “definitive suicidal behavior/ideation.” It was this finding that received all the media attention. But not mentioned in the coverage was how this elevated risk emerged only when two discrete categories, “suicidal behavior” and “suicidal thinking,” were combined to make a third, composite category called “definitive suicidal behavior/ideation.”

Separately, neither of the two discrete categories showed a statistically significant elevation for subjects taking medication. Combining data from separate categories is not necessarily a problem, but when the original results are inconclusive in the first place, the finding is less than convincing.

None of this is to say that anti-depressants are harmless. As early as 1960, psychiatrists were aware that anti-depressants called tricyclics could precipitate suicide in some patients. The neurotransmitter changes they induced often caused the patient’s energy to return before his hopelessness faded. Patients no longer immobilized by their misery now had enough energy to end it. Another small fraction of patients could flip into mania or a manic psychosis, or develop a severe form of agitation (akathisia) that might also trigger a suicide attempt. This is why standard teaching for beginning psychiatry residents emphasizes that they watch patients very closely when starting an anti-depressant.

In the mid-80s, the SSRI drugs came on the scene. Eventually they too were observed to spark suicidal activity and akathisia in a small percentage of patients. What is significantly different now, however, is that the medications are increasingly used to treat children and adolescents. What’s more, the primary-care doctors and pediatricians who regularly prescribe these medications for children may do so for minor conditions or they may not always monitor the patients closely enough, or both.

The current controversy stems from uncertainty over whether the risks of the medications are offset by their benefits. From a research perspective, those benefits do not appear to be overwhelming. (Prozac seems to fare somewhat better than other SSRIs.) In pediatric trials of depression, the drugs are only slightly more effective than placebo. Some experts believe that this is because the sickest — and most medication-responsive — children are often excluded from participating. This leaves too many subjects enrolled in clinical trials with relatively mild to moderate depressions that would get better without medication. But clinical experience tells us that some children are helped immensely by anti-depressants. This is why many doctors and parents swear by them.

What we need are studies designed to assess aggravation of suicidal thoughts and behavior in kids who are already suicidal, and we don’t have those yet. Nor do we have studies that look at the long-term effects of treatment on the risk of suicide.

But it is not enough to ask how many suicides are associated with SSRIs; just as important is the question, how many suicides are prevented because of these drugs? Sadly, there is much to prevent. A 1999 study in the Journal of the American Medical Association reported on a group of depressed adolescents 15 years after diagnosis. Within that time, half had attempted suicide and 7 percent succeeded. According to the surgeon general, at least half of all clinically depressed children are not getting any treatment at all.

In the meantime, epidemiologic trends raise the possibility that anti-depressants have helped prevent youth suicide. If many young people were committing suicide as a side effect of medication, it seems reasonable that we would see a spike in the adolescent suicide rate. “In fact, we’re seeing the exact opposite,” says David Fassler, child psychiatrist at the University of Vermont. “Since the early 1990s, the incidence of suicidal ideation among adolescents is down over 40 percent, and actual suicides are down over 25 percent, according to the Centers for Disease Control.”

Along these lines, a study in the Archives of General Psychiatry last year looked at the numbers of anti-depressant prescriptions written for youths according to zip codes across the country and compared them with census data on youth suicide. The greater the increase in the prescriptions in particular geographic areas, the sharper the reduction in the teen-suicide rates in those locations over the last decade. Though an intriguing finding, the study did not control for potential risk factors such as substance use and so cannot be said to constitute definitive proof.

Anyone looking for clear and simple answers here will be frustrated. Of course, that provides no solace to parents who have lost a child. But the emotional weight of the issue must not deform facts, drive public policy, or stymie further research. It is clear that authentic major depression in children is a serious matter. Accurate diagnosis and careful treatment will save many more lives than might be lost through the use of these drugs.

–Sally Satel is a resident scholar at the American Enterprise Institute. This is an expanded version of an op-ed that appeared in the Wall Street Journal on Sept. 10.