Sudden cardiac and sudden unexpected death related to antipsychotics: A meta‐analysis of observational studies

Abstract

To estimate the risk of sudden cardiac death (SCD) or sudden unexpected death (SUD) related to individual antipsychotics, a meta-analysis of observational studies was performed. Adjusted odds ratio (OR) of SCD/SUD with 95% confidence intervals (CI) were extracted and pooled; heterogeneity was studied using Q statistic and I(2) index, and its potential causes (e.g., hERG blockade potency) explored using meta-regression. Two cohort (740,306 person-years) and four case-control (2,557 cases; 17,670 controls) studies, investigating nine antipsychotics, were included. Compared with nonusers, the risk was increased for quetiapine (OR = 1.72, 95% CI: 1.33-2.23), olanzapine (OR = 2.04, 1.52-2.74), risperidone (OR = 3.04, 2.39-3.86), haloperidol (OR = 2.97, 1.59-5.54), clozapine (OR = 3.67, 1.94-6.94), and thioridazine (OR = 4.58, 2.09-10.05). Heterogeneity was found (Q = 20.0, P = 0.01; I(2) = 60.0%), and the increasing mean hERG blockade potency (P = 0.01) accounted for 43% of this. The SCD/SUD risk differed between individual antipsychotics, and mean hERG blockade potency could be an explanatory factor. This should be considered when initiating antipsychotic treatment.

Metabolic Response to Olanzapine in Healthy Chinese Subjects with rs7093146 Polymorphism in Transcription Factor 7‐like 2 Gene (TCF7L2): A Prospective Study

“…Large public health studies have demonstrated that cardiovascular disease (CVD) is the single largest cause of death in patients with schizophrenia [44,45]. The use of AAPs such as olanzapine may cause dyslipidaemia, which is one of the major causes of CVD and of mortality in patients with mental illness [46,47]. In the present study, acute olanzapine treatment significantly increased the plasma triglycerides level in both the subjects with rs7903146 and those without.…”

Two Sudden and Unexpected Deaths of Patients with Schizophrenia Associated with Intramuscular Injections of Antipsychotics and Practice Guidelines to Limit the Use of High Doses of Intramuscular Antipsychotics

“…The outcome of that decision, based on “limited” case reports would probably have led to saving hundreds or thousands of lives worldwide during the last 30 years. Psychiatrists would have prescribed other antipsychotics with less risk for TdP rather instead of prescribing thioridazine, which may be the oral antipsychotic that most frequently causes sudden death [58]. Similarly, it would be a mistake to ignore the risk of TdP associated with high doses of haloperidol IM, suggested by our 2 case reports.…”

Evidence for the hERG Liability of Antihistamines, Antipsychotics, and Anti‐Infective Agents: A Systematic Literature Review From the ARITMO Project

“…First, there may be gaps in the clinical knowledge compiled by AZCERT because much of the published literature on TdP risk is based on case reports, which vary in context and completeness of information. There are relatively few formal controlled studies, and these focus on a drug's potential to prolong the QT interval as a surrogate marker for TdP, whereas larger‐scale observational studies tend to measure broader outcomes such as sudden cardiac death . Second, there may be gaps in the available hERG data because this is not always available in the public domain.…”