The article "Cardiac Death Risk Rises With Both Antipsychotic Types" in the March 6 issue is correct when it points out that there is no safety advantage to second-generation antipsychotics (SGAs). Its headline, however, is misleading since it suggests that there is not much difference between the two groups. Such interpretation of the study is questionable.

The first-generation antipsychotics (FGAs) include drugs ranging from haloperidol, the drug with the lowest risk ratio of 1.61, to thioridazine, the drug with the second highest risk ratio of 3.19. Thioridazine is notorious for its association with sudden, unexplained death. A British study puts the odds ratio at 5.3. For this reason thioridazine is banned in Great Britain and is available in the United States only with a black-box warning. Inclusion of thioridazine, which should never be used, increases the risk ratio for the whole FGA group inordinately.

In fairness, it ought to be pointed out that the SGA group contains the drug with the highest risk ratio—clozapine, with a risk ratio of 3.67. However, the number of patients on clozapine is only 6 percent of the SGA group, while the number of patients on thioridazine in the FGA group is 18 percent, thus causing a much larger distortion.

Even with this distortion, the combined risk ratios for FGAs are lower than those for SGAs at all three dosages, although to a degree that is not statistically significant.

The interpretation of the study by Wayne Ray and colleagues is incomplete without pointing out that haloperidol, the most popular of FGAs, remains what it has always been—the safest antipsychotic in terms of cardiovascular toxicity.


MIODRAG RISTICH, M.D.
 New York, N.Y.