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Letter to the Editor

Dr Manu Replies

Peter Manu, MDa

Published: November 17, 2020

See letter by Finsterer et al and article by Manu et al

To the Editor: Dr Finsterer and colleagues question data, derived from a retrospective cohort study my colleagues and I published 10 years ago,1 regarding sudden deaths among patients receiving care in a psychiatric institution that found that a plurality of deaths were due to cardiovascular causes, primarily coronary artery disease. They think that we had no mandatory protocol for establishing the cause of death and that we did not present information regarding “a number of risk factors” for sudden death. They seem to be particularly concerned about the absence of embolic stroke among the causes of sudden death identified in our 100-case cohort, because they felt that “it is conceivable that that some of the 100 patients had atrial fibrillation, severe heart failure, dilated cardiomyopathy, noncompaction, patent foramen ovale, or Takotsubo syndrome.” They also wondered how many of the patients included in the cohort had electrocardiograms prior to sudden death.

Before addressing the specific comments, I need to present the background of our work, which was the publication, in 2009, in the New England Journal of Medicine, of a retrospective cohort study2 that indicated a significantly higher risk of sudden cardiac death among persons who had been prescribed antipsychotic drugs. This highly influential study was based of death certificates and was conducted by epidemiologists, and it concluded that the excess of sudden dying may have been due to the known effect of antipsychotic drugs on myocardial repolarization leading to lethal ventricular arrhythmia. Our data indicated that unexplained sudden deaths in psychiatric patients were not associated with higher utilization of first- or second-generation antipsychotics.

Contrary to to the impression of Dr Finsterer and colleagues, our study was based on a structured protocol of multidisciplinary root cause analysis with access to all relevant information and expert opinions. The process was described in detail in our work. We also made clear in our publication that in each case all available electrocardiograms, which were recorded for all according to our hospital’s policy, were carefully reviewed to determine the corrected QT interval and all other significant abnormalities.

We had no reason to doubt the fact that work using structured root cause analyses was clearly superior to that based on death certificates. However, in this cohort, only 18 of the 100 patients were accepted by the Medical Examiner of the City of New York for autopsy and the report made available to the root cause analysis team. In a study published a few years later,3 we evaluated data derived from another cohort of patients, all diagnosed with schizophrenia, who died suddenly while admitted for psychiatric care. For that cohort, autopsy data were available in 51 of 57 cases and indicated that in a majority of cases the cause of death was myocardial infarction.

The absence of embolic strokes among the causes of death identified by us is related to the rarity of this association. In the only large study available,4 among 255 deaths caused by a first stroke, 52 were sudden, but only 2 were due to cortical or pontine infarction. All other stroke-related sudden deaths were associated with primary intracerebral or subarachnoid hemorrhages.


1.Manu P, Kane JM, Correll CU. Sudden deaths in psychiatric patients. J Clin Psychiatry. 2011;72(7):936-941. PubMed CrossRef

2.Ray WA, Chung CP, Murray KT, et al. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med. 2009;360(3):225-235. PubMed CrossRef

3.Ifteni P, Correll CU, Burtea V, et al. Sudden unexpected death in schizophrenia: autopsy findings in psychiatric inpatients. Schizophr Res. 2014;155(1-3):72-76. PubMed CrossRef

4.Phillips LH, Whisnant JP, Reagan TJ. Sudden death from stroke. Stroke. 1977;8(3):392-395. PubMed CrossRef

Peter Manu, MDa

aDonald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.

Published online: November 17, 2020.

Potential conflicts of interest: None.

Funding/support: None.

J Clin Psychiatry 2021;82(1):20lr13623a

To cite: Manu P. Dr Manu replies. J Clin Psychiatry. 2021;82(1):20lr13623a.

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