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October 21, 2025Forensic Science Medicine and Pathology4 citationsOpen Access

Sudden cardiac death in young adults and the role of antipsychotic drugs: a multicenter autopsy study

MEMassimiliano EspositoUniversità degli Studi di Enna KorePZPietro ZuccarelloPegaso UniversityFSFrancesco SessaPegaso University

Key Result

Chronic use of antipsychotic drugs in young adults with schizophrenia was associated with structural cardiac changes, including myocardial fibrosis and contraction band necrosis, predisposing them to sudden cardiac death.

Study Design

Type

Observational (n=7)

Multicenter

Yes

Structured PICO

Does chronic antipsychotic drug therapy induce structural cardiac changes predisposing to sudden cardiac death in young adults with schizophrenia?

P
Population
7 young adults (aged 18-39) with schizophrenia chronically treated with antipsychotic drugs who died from sudden cardiac death, free of traditional cardiovascular risk factors.
E
Exposure
Chronic treatment with antipsychotic drugs (APDs), with toxicological confirmation of therapeutic levels (polypharmacy commonly observed, including haloperidol, quetiapine, clozapine, promazine, aripiprazole).
O
Outcome
Structural cardiac changes (macroscopic and histological) and toxicological findings in postmortem examination.surrogate

Chronic antipsychotic drug use in young adults with schizophrenia is associated with structural cardiac changes, such as myocardial fibrosis and contraction band necrosis, which may predispose to sudden cardiac death even without traditional cardiovascular risk factors.

Limitations

  • Limited sample size due to stringent inclusion criteria
  • Inclusion of only one female participant
  • Lack of genetic analysis to evaluate predispositions to sudden cardiac death
  • Polytherapy patterns prevented assessment of individual antipsychotic drug cardiotoxicity
  • Absence of specialized stains like Masson's trichrome
  • Small sample size
  • Polytherapy patterns limit the ability to identify specific APDs responsible for cardiac toxicity
  • Lack of genetic testing and molecular autopsies

Abstract

Sudden cardiac death (SCD) in patients with schizophrenia treated with antipsychotic drugs (APDs) has become a significant concern, with increasing incidence, particularly among young adults. This multicenter study aimed to investigate the cardiac effects of APDs in a cohort of patients who died from SCD. A retrospective analysis was conducted on seven schizophrenic patients, aged 25 to 39 years, who died from SCD while receiving antipsychotic therapy. Patients with cardiovascular risk factors, substance abuse at the time of death, or advanced age were excluded. Autopsies focused on cardiac tissue, and histological and toxicological analyses were performed. The findings revealed structural cardiac changes, including myocardial fibrosis, myofiber disruption, and contraction band necrosis-features consistent with arrhythmic SCD. Toxicological results confirmed APD use in all cases, with polypharmacy patterns commonly observed. The study suggests that APDs can induce significant cardiac alterations that may predispose patients to SCD, even in the absence of pre-existing cardiac disease. These findings underscore the need for careful cardiac monitoring in patients with schizophrenia treated with APDs, particularly those without traditional cardiovascular risk factors. Further research, including molecular autopsy and genetic analysis, is necessary to better understand genetic predispositions and the role of APDs in SCD.

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Cite This Study

Esposito et al. (2025) conducted an observational in Schizophrenia and sudden cardiac death (n=7). Antipsychotic drugs was evaluated on Histological and toxicological cardiac findings. Chronic use of antipsychotic drugs in young adults with schizophrenia was associated with structural cardiac changes, including myocardial fibrosis and contraction band necrosis, predisposing them to sudden cardiac death.

synapsesocial.com/papers/6a1fe9290a77fb36002e470dhttps://doi.org/10.1007/s12024-025-01096-3
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