Cardiovascular safety of antipsychotics: a clinical overview

ABSTRACT

Introduction: Although antipsychotics have been associated with sudden cardiac death (SCD), they still remain a cornerstone in the treatment of psychiatric patients. Most antipsychotics have an unfavorable cardiovascular adverse effect profile, and SCD may occur even in patients with no cardiovascular risk factors.

Areas covered: This clinical overview summarizes the cardiovascular safety of antipsychotics by focusing on the wide range of associated adverse effects. In addition, we also discuss current guidelines regarding routine electrocardiogram (ECG) monitoring.

Expert opinion: As SCD in psychiatric patients is multifactorial, the contribution from antipsychotic treatment remains largely unknown. Cardiovascular adverse effects of antipsychotics vary substantially, even when used in therapeutic doses. Currently, most clinical concern focuses on antipsychotic-induced corrected QT prolongation, as this may increase risk of Torsades de Pointes and eventually SCD. However, other serious cardiovascular adverse effects of antipsychotics also include Brugada syndrome phenotype, myocardial infarction, and myocarditis. Increased awareness of the cardiovascular safety of antipsychotics can allow physicians to better manage and monitor high-risk patients. In this patient group, ECG monitoring may be warranted and other examinations symptom driven. Prescription of antipsychotics should always be a balance between the perceived clinical effect and the burden of adverse effects.

KEYWORDS:

• Adverse effects
• antipsychotics
• cardiovascular safety
• ECG monitoring
• QTc prolongation
• sudden cardiac death

Article highlights

• The corrected QT (QTc) interval remains the most widely used surrogate marker for assessing risk of Torsades de Pointes and eventually sudden cardiac death (SCD), but it is considered rather imprecise.

• In patients on antipsychotics, SCD risk is more than doubled due to increased risk of weight gain, dyslipidemia, type 2 diabetes mellitus, smoking, alcohol abuse, poor diet, sedentary lifestyle, and stress, some of which may be related to antipsychotic treatment.

• Polypharmacy, drug doses above recommended therapeutic ranges, exposure to drugs of abuse such as central nervous system stimulants, and attempted suicide with overdose may also contribute to increased SCD risk in this patient group.

• Aripiprazole is associated with a low risk of sinus tachycardia (ST), orthostatic hypotension (OH), and QTc prolongation.

• Olanzapine is associated with a moderate risk of ST, OH, hypertension, and QTc prolongation.

• Clozapine is associated with a high risk of ST, OH, and hypertension. Evidence of clozapine-induced myocarditis and cardiomyopathy is also considered strong, although the incidence is rather low.

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Financial & competing interests disclosure

K Kragholm has received research grants from the Laerdal Foundation. O Schjerning has received speaking fees from H. Lundbeck. J Nielsen has received research grants from H. Lundbeck and Pfizer for clinical studies, as well as speaking fees from Bristol-Myers Squibb, H. Lundbeck, and Hemocue. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.