Older antipsychotic drugs as effective, offer fewer side effects in children than newer drugs, study finds

The two most frequently prescribed antipsychotic drugs for children and adolescents offer no additional benefit and are more likely to cause side effects than an older, less costly medication, according to a National Institute of Mental Health study published on Monday, the New York Times reports.

Prescription rates for Eli Lilly's Zyprexa and Janssen's Risperdal , known as atypical antipsychotics, have increased more than fivefold in the last 15 years and now are used to "settle outbursts and aggression in children with a wide variety of diagnoses, despite serious side effects," the Times reports. Both drugmakers noted that the medications are not approved for use in children.

For the study, Linmarie Sikich of the University of North Carolina-Chapel Hill and colleagues examined 119 people ages eight to 19 who experienced psychotic symptoms. The participants received either Zyprexa, Risperdal or molindone, an older drug used to lessen the effects of psychosis. Neither doctors nor the children knew what drug each was taking, but children were allowed to stop taking medications at any time or switch to a different drug. After eight weeks, 34% of children taking Zyprexa, 46% of those taking Risperdal and 50% of those taking molindone reported significant improvements. However, by this time, half of the participants had elected to stop taking the drugs because of side effects, so "it was not clear that those differences were significant," the Times reports. Participants in the Zyprexa group gained an average of 13 pounds, while the Risperdal group showed average weight gain of nine pounds and the molindone group gained less than a pound on average.

Sikich said, "One implication of this study is that the guidelines for treating schizophrenia need to be revised, so that some of the milder, traditional or older medications are considered first-line treatments in some cases." She added, "The other significant thing is that none of these medications were as well tolerated as we had hoped. We really need to find better alternatives." Sanjiv Kumra, director of the division of child and adolescent psychiatry at the University of Minnesota, who was not involved in the study, said, "This is really a landmark study, because these newer drugs have been around for 12 years or so now, and there were fundamental questions for which we really didn't have answers." According to Kumra, "What this is saying is that all treatments work, at least for some people, and have serious risks for others," so it is a "trial-and-error process" to match people with the right drug.

The results of the study are likely to affect treatments for an estimated one million children and "intensify a broader controversy in child psychiatry over the newer medications," according to the Times. A consortium of state Medicaid directors currently is evaluating the use of atypical antipsychotics in child beneficiaries to ensure the drugs are being prescribed appropriately (Carey, New York Times, 9/15).

Opinion Piece

FDA's "refusal to withdraw its off-putting 'black-box' warning label on antidepressants for teens" has led to a "decline in physician prescribing ... of safe and effective antidepressants -- and the rate of teen suicide rose to a historic, and tragic degree," Gilbert Ross, an executive and medical director of the American Council on Science and Health, writes in a Washington Times opinion piece. He notes that in FDA evaluations, "[n]o actual suicides occurred, only thoughts about suicide." He continues, "Studies done over the ensuing years confirmed the obvious: Fewer prescriptions were written for these safe and effective drugs." According to Ross, "Defensive FDA talk last year about a 'chance spike' in teen suicides is refuted by these new data, which confirm a real increase."

According to Ross, experts in teen depression "continue to petition the regulators to remove the warning label." However, Ross notes that FDA spokesperson Sandy Walsh said, "We never intended to discourage appropriate prescribing," adding, "It's still good advice to monitor patients starting treatment." Ross writes, "If she actually wanted to benefit public health ... she should stop lecturing doctors and instead tell her bosses ... that the time is long past when the inappropriate warning label on antidepressants should be removed." Ross concludes, "Every day it remains -- frightening parents, teens and doctors -- costs a youngster his or her life," and "[t]hese are real lives, not hypothetical ones" (Ross, Washington Times, 9/14).