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Drs. Tandon and Constantine reply

Vol. 6, No. 1 / January 2007

We thank Dr. Helmuth and the principal investigators of CATIE for their interest in our article and the opportunity to further clarify a key learning point from CATIE.

Dr. Helmuth acknowledges our balanced review but suggests that cost and metabolic side effects should be considered along with lower EPS liability in selecting antipsychotic therapy. We agree. Avoiding EPS while obtaining a good antipsychotic effect is one key consideration in providing optimal antipsychotic therapy. Other adverse effects, patient preference, cost, and other factors are all important considerations in this complex process of individually optimizing antipsychotic treatment.

The CATIE investigators agree with our interpretation of the study’s principal findings. They take exception, however, to our suggestion that CATIE’s finding of no FGA-SGA difference in EPS and TD may be related to its relatively low assay sensitivity to detect such differences because the sample studied was at low risk for EPS and TD.

While accepting our description of the study sample as accurate, they disagree that it was at low risk for EPS and TD. Patients who have been ill for 16 years and received antipsychotic treatment for an average of 14 years without developing TD or severe EPS (as in CATIE) are by definition at low risk for EPS and TD.

We agree that patients without current TD and who are at risk for developing it comprise the best study population to investigate differential risk for TD; however, patients who have not developed it, despite 14 years of antipsychotic therapy, are at very low risk for developing it at all. First-episode patients without prior antipsychotic exposure would be an optimal study population, but such patients were excluded from CATIE.

Drs. Rosenheck and colleagues do not disagree with any of the other assertions in our article; they are, however, critical of “numerous factual errors in other published critiques of CATIE.” We cannot address such supposed inaccuracies, which are best taken up with authors of those commentaries.

To extract maximum value from this important initiative, we must better understand CATIE’s findings in the context of its study design and the results of other relevant studies. Neither mischaracterization nor overinterpretation of CATIE’s findings helps clinicians, patients, and policy-makers.

The essence of our article was that avoiding motor, cognitive, and affective EPS due to unmodulated dopamine blockade is the key to realizing the “atypical benefits” of a broader spectrum of efficacy and lower risk of TD during antipsychotic therapy. Neither Dr. Helmuth nor Drs. Rosenheck and colleagues appear to disagree with this assertion. Avoiding broadly defined EPS appears to be critical to improving cognition, dysphoria, and negative symptoms with SGAs and FGAs. The lower risk of TD observed with SGAs also appears to be related to the greater ease with which they can provide an equivalent antipsychotic effect without EPS.

Rajiv Tandon, MD
Adjunct professor of psychiatry
University of Florida, Tallahassee

Robert Constantine, PhD
Research associate professor
University of South Florida, Tampa

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