Sudden death in schizophrenia

To examine the recent literature regarding sudden death in patients with schizophrenia and synthesize salient conclusions based on this evidence.

Sudden cardiac death (SCD) is the largest subset of sudden unexpected death (SUD), with up to 40% of SUD from cardiovascular causes. SCD has been associated with exposure to both first and second-generation antipsychotics. Clozapine [odds ratio (OR) 3.67, 95% confidence interval (CI) 1.94-6.94] confers the highest risk of SCD followed by risperidone (OR 3.04, 95% CI 2.39-3.86) then olanzapine (OR 2.04, 95% CI 1.52-2.74). SCD not associated with antipsychotic use has been correlated to several modifiable and nonmodifiable risk factors - obesity, smoking, dyslipidemia, diabetes, hypertension, age, sex, and history of cardiovascular disease. Other subsets of SUD include hematological and pulmonary causes, including agranulocytosis leading to sepsis, deep vein thrombosis leading to pulmonary embolisms, and aspiration pneumonia leading to sepsis.

There is a huge paucity in genetic and pharmacogenetic data focused on SUD in schizophrenia. Future studies should emphasize the genetic aspects as well as clarify the underlying molecular mechanisms of these pathways. Additionally, early detection of those patients at high risk for SUD and discovery of preventive measures should also be emphasized.