Yet Another Disappointment: First CATIE, and Now the 12-Month Results from TEOSS in Children
The NIMH's CATIE trial of antipsychotics for adult schizophrenia is regularly understood to have shown that atypical antipsychotics are "no better" than the old standard antipsychotics. The CATIE study was one of several government-funded trials, here in the United States and in the United Kingdom, to come to that finding. But another conclusion to draw from CATIE is that neither the old drugs or the new ones can really be said to "work" for most patients, given that 74% of the 1,432 patients in the trial stopped taking the assigned antipsychotic within 18 months, mostly because of "intolerable side effects" or the drug's "inefficacy."
Now the 12-month results from the NIMH-funded "Treatment of Early-Onset Schizophrenia Spectrum" study are about to be published, and, unfortunately, in this age group (eight to nineteen years old), the results are even more disappointing. Only 14 of the 116 youth (12%) responded to the study medication and were able to successfully stay on it for one year. In other words, the 74% failure rate in adults climbed to 88% in youth. The results will be published in the June issue of the Journal of the American Academy of Child & Adolescent Psychiatry (and have already been published by the journal online.)
The TEOSS study was not placebo-controlled. The 116 youth entrolled into the trial were randomized either to a standard antipsychotic (molindone) or to an atypical antipsychotic (olanzapine or risperidone.) The investigators hypothesized that "treatment with olanzapine and risperidone would be associated with greater treatment response and greater tolerability than treatment with molindone," but that did not turn out to be the case. At the end of eight weeks, the response rate was 50% for those treated with molindone, 46% for risperidone, and 34% for olanzapine. Adverse events were "frequent" in all three groups.
Only those youth who "responded" during the initial eight weeks -- 54 of the 116 -- were entered into the 44-week maintenance study. Forty of the 54 youth dropped out during this period because of "adverse effects" or "inadequate response." Thus, only 14 of the 116 youth who entered the study responded to the study medication and stayed on it for as long as one year.
These study results are disturbing for three reasons.
First, as is well known, the prescribing of antipsychotics to youth took off in the mid 1990s based on a belief, among psychiatrists, that the atypicals were safer and more efficacious than the old drugs. CATIE showed that not to be true in adults, and now we see the same thing in youth. So this trial tells of prescribing patterns that arose from a delusion, and that generally is not a recipe for good medicine.
Second, we see in the 12-month results evidence of a failed therapy. The bottom-line might be summed up this way: The drug treatment could be said to have worked for 12% of the patients, and to not have worked for the remaining 88%.
Third, we now have to ask this question about the youth in the latter category: Was the drug treatment therapeutically "neutral" for the 88% who tried one of the three antipsychotics and then couldn't stay on that drug for a year, or was the treatment ultimately "harmful," given that antipsychotics can cause so many troubling side effects? In other words, would these patients -- 102 of the original cohort of 116 in the trial -- have been better off at the end of one year if they had been treated from the beginning with a non-drug therapy, instead of an antipsychotic?
The TEOSS trial can't answer that question. But it's clearly one that needs to be asked.
Tuesday, May 25, 2010
