Sudden cardiac and sudden unexpected death related to antipsychotics: A meta-analysis of observational studies.
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.
University of Bordeaux, INSERM U657, Bordeaux, France.|CHU Bordeaux, Bordeaux, France.
F
F
Salvo
University of Bordeaux, INSERM U657, Bordeaux, France.|CHU Bordeaux, Bordeaux, France.|CIC Bordeaux CIC1401, Bordeaux, France.
A
A
Pariente
Drug Safety Research Unit, Southampton, Hampshire, UK.
S
S
Shakir
CIC Bordeaux CIC1401, Bordeaux, France.|ADERA, Pessac, France.
P
P
Robinson
University of Bordeaux, INSERM U657, Bordeaux, France.
M
M
Arnaud
Medical Toxicology Centre, Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
Shl
S
Thomas
Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
E
E
Raschi
University of Bordeaux, INSERM U657, Bordeaux, France.|CHU Bordeaux, Bordeaux, France.
A
A
Fourrier-Réglat
University of Bordeaux, INSERM U657, Bordeaux, France.|CHU Bordeaux, Bordeaux, France.|CIC Bordeaux CIC1401, Bordeaux, France.
N
N
Moore
Department of Medical Informatics, Erasmus University Medical Centre, Rotterdam, Netherlands.
M
M
Sturkenboom
Drug Safety Research Unit, Southampton, Hampshire, UK.
L
L
Hazell On Behalf Of Investigators Of The Aritmo Consortium
D014150:Antipsychotic Agents / Q000009:adverse effects*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology* / Q000209:etiology*; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors; D006801:Humans; D020128:Inhibitory Concentration 50; D064887:Observational Studies as Topic
D014150:Antipsychotic Agents; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human