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Sudden cardiac and sudden unexpected death related to antipsychotics: a meta-analysis of observational studies

Sudden cardiac and sudden unexpected death related to antipsychotics: a meta-analysis of observational studies
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.

0009-9236
306-314
Salvo, F.
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Pariente, A.
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Shakir, S.
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Robinson, P.
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Arnaud, M.
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Thomas, S.H.
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Raschi, E.
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Fourrier-Reglat, A.
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Moore, N.
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Sturkenboom, M.
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Hazell, L.
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Salvo, F.
2e7651c7-4c18-4dc2-9a95-923bb32d2507
Pariente, A.
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Shakir, S.
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Robinson, P.
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Arnaud, M.
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Thomas, S.H.
01001c3b-1010-479b-aeeb-5157c637e319
Raschi, E.
d851b687-ff98-4e41-8228-037048e63168
Fourrier-Reglat, A.
41580357-bbbf-4cbc-9398-00199b55695d
Moore, N.
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Sturkenboom, M.
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Hazell, L.
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Salvo, F., Pariente, A., Shakir, S., Robinson, P., Arnaud, M., Thomas, S.H., Raschi, E., Fourrier-Reglat, A., Moore, N., Sturkenboom, M. and Hazell, L. (2016) Sudden cardiac and sudden unexpected death related to antipsychotics: a meta-analysis of observational studies. Clinical Pharmacology and Therapeutics, 99 (3), 306-314. (doi:10.1002/cpt.250).

Record type: Article

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.

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More information

Accepted/In Press date: 9 August 2015
e-pub ahead of print date: 20 November 2015
Published date: 1 March 2016

Identifiers

Local EPrints ID: 438868
URI: http://eprints.soton.ac.uk/id/eprint/438868
ISSN: 0009-9236
PURE UUID: 64074184-28cc-4451-abf9-0cf02394a5b8
ORCID for L. Hazell: ORCID iD orcid.org/0000-0002-5962-0648

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Date deposited: 25 Mar 2020 17:52
Last modified: 10 May 2024 16:59

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Contributors

Author: F. Salvo
Author: A. Pariente
Author: S. Shakir
Author: P. Robinson
Author: M. Arnaud
Author: S.H. Thomas
Author: E. Raschi
Author: A. Fourrier-Reglat
Author: N. Moore
Author: M. Sturkenboom
Author: L. Hazell ORCID iD

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