Introduction

Studies using death certificates have indicated an excess of sudden cardiac deaths among users of antipsychotic drugs compared to the general population, but may have underestimated the presence of other known causes of sudden and unexpected death.

Objectives

To assess the cause and risk factors for sudden death discovered by contemporaneous investigation of all deaths occurring over a 26-year period (1984–2009) in adult patients registered for care in one large psychiatric hospital in New York.

Methods

Circumstances of death, psychiatric diagnoses, psychotropic drugs and past medical history were extracted from the root cause analyses of sudden unexpected deaths. After the exclusion of suicides, homicides and drug overdoses, explained and unexplained cases were compared regarding clinical variables and the utilization of antipsychotics.

Results

One hundred cases of sudden death were identified among of 119, 500 patient-years. The death remained unexplained in 52 cases. The incidence of unexplained sudden death was 125/100,000 (95% CI 88.9–175.1/100,000) patient-years in 2005–2009, 53/100,000 (95% CI 31.7–88.5/100,000) patient-years in 1999–2004 and 7/100,000 (95% CI 3.7–19.4/100,000) patient-years in 1984–1998. Explained and unexplained cases were similar regarding psychiatric diagnoses and treatment with any psychotropic class, including first- and second-generation antipsychotics. Dyslipidemia (p = 0.012), diabetes (p = 0.055) and co-morbid dyslipidemia and diabetes (p = 0.008) were more common in the unexplained than in the explained cases.

Conclusions

In a consecutive cohort of psychiatric patients, the unexplained sudden deaths were associated with known risk factors for coronary artery disease, but not with higher utilization of first- or second-generation anti-psychotics.

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Psychiatric patients are at greater risk of sudden death,
with a 3–5 fold increase compared with the nonpsychiatric
population. Sudden death may arise from complications of
the mental illnesses or as a result of psychotropic
medication. Anorexia nervosa, drug use, alcohol misuse
are the mental disorders most likely associated with
sudden death. A variety of psychotropic drugs,
particularly antipsychotic agents and tricyclic
antidepressants are associated with sudden death.
Inducing cardiac arrhythmias are one of the most likely
mechanisms of sudden death because of electric
membrane alterations induced by psychotropic drugs,

resulting in electrocardiogram changes. Psychotropic
medication is not necessarily causative for excess
mortality in psychiatric patients as higher doses might be
linked with mortality through a contradictory factor such
as worse physical condition in people with more serious
mental health problems. Compared with non-suicide
mortality, the number of deaths that might be attributable
to medication is small, but according to most researchers,
iatrogenic mortality must be taken seriously, with
appropriate steps taken towards prevention.
Key words: unexpected death; mental illnesses; QT
interval prolongation.

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