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Switching Drugs No Panacea in Schizophrenia


NEW YORK -- For many schizophrenia patients, switching antipsychotic drugs may improve symptom control with fewer side effects. But other patients, already doing well, may be better off standing pat, showed a randomized trial.

NEW YORK, Dec. 1 -- For schizophrenia patients already doing well on antipsychotic medication, switching drugs to improve symptom control may backfire.

In a large prospective study, many patients who were randomly assigned to continue the same medication they were already on did better than those who were switched, Susan Essock, Ph.D., of Mount Sinai here, and colleagues, reported in the December issue of the American Journal of Psychiatry.

"The stayers did better, which underscores the risk associated with changing anti-psychotic medications," Dr. Essock said during a press conference.

The finding came from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial, which compared Trilafon (perphenazine) with four so-called second generation medications, Zyprexa (olanzapine), Geodon (ziprasidone), Seroquel (quetiapine fumarate), and Risperdal (risperidone).

The main result of the study, published last September, was that Zyprexa had the lowest rate of discontinuation, but that Trilafon was comparable to the other three and "not than much less effective than olanzapine," said principal investigator Jeffrey Lieberman, M.D., of Columbia University.

Dr. Essock, not part of the original CATIE research team, employed data from the first phase of the study to look at the question of switching medication, using the same endpoint as the overall trial - time to discontinuation of medication for any reason.

Her report is one of two secondary analyses of the CATIE data published in the December issue of the journal. The other, from researchers led by Robert Rosenheck, M.D., of Yale, examined the relative cost-effectiveness of the study drugs.

Dr Essock said the urge to change medications is understandable, because most patients are "partial responders," and the new study shouldn't discourage physicians from trying new avenues.

But, she said, doctors "should make all efforts to optimize the current regimen for patients" before switching.

Because Zyprexa and Risperdal were widely used when CATIE started in 2000, Dr. Essock and colleagues said, many patients entering the trial were already using them. Such patients were dubbed "stayers" if they were randomly assigned to continue on the same medication. "Switchers" were those who were randomly assigned to either medication from another drug.

Analysis showed that 77 of 314 patients (or 25%) assigned to Zyprexa and 62 of 321 (or 19%) patients assigned to Risperdal were stayers, Dr. Essock said.

The researchers found that Zyprexa stayers had an all-cause discontinuation rate of less than 50%, compared with nearly 70% for those switched to it from another drug drug. Risperdal stayers had a discontinuation rate of about 67%, compared with more than 85% for those switched to it from another drug.

The median times to discontinuation reflected the same picture:

  • Risperdal stayers remained on the drug for 8.4 months
  • Zyprexa switchers lasted 7.7 months
  • Risperdal switchers lasted 4.7 months.

Because of a relative lack of discontinuations, the researchers were unable to pin down the median time for Zyprexa stayers, but said it was greater than 11.6 months with 95% certainty.

Because of the size of the effect, the researchers re-analyzed the original CATIE data without the stayers and found that the overall picture was unchanged, although because of the smaller sample size, statistical significance was weakened.

The new analysis "adds unexpectedly valuable information" despite some limitations, according to the journal's deputy editor, Carol Tamminga, M.D., of the University of Texas Southwestern Medical Center in Dallas.

In an accompanying editorial, Dr. Tamminga and colleagues said the study tells physicians and their patients that "switching is a not a risk-free decision for the patient."

On the other hand, they said, the study does not address the issue of switching medications early in the course of the disease, because CATIE participants had on average been treated for 14 years at the time of the study.

The authors noted several other limitations of the study in addition to the sample size, which limited the number of drugs that could be evaluated.

"The post hoc analyses were exploratory and, as such, carry concerns about spurious findings from multiple comparisons," they wrote. "Thus, the results should be interpreted as preliminary."

"Dosages of the medications in the double-blind condition may have advantaged some medications (e.g., olanzapine) and not others (e.g., quetiapine and ziprasidone)," they added.

It is not surprising, Dr. Tamminga and colleagues said, that many patients were already on a drug that suited them better than others, so that switching worsened their condition.

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