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