Electrocardiogram Alterations Associated With Psychotropic Drug Use and CACNA1C Gene Variants in Three Independent Samples

Chiara Fabbri, Giuseppe Boriani, Igor Diemberger, Maria Giulia Filippi, Gloria Ravegnini, Patrizia Hrelia, Alessandro Minarini, Diego Albani, Gianluigi Forloni, Sabrina Angelini, Alessandro Serretti

Research output: Contribution to journalArticle

Abstract

Several antipsychotics and antidepressants have been associated with QTc prolongation or other electrocardiogram (ECG) alterations, but their impact is still debated and other risk factors are known to affect QTc. We investigated the effect of antidepressants and antipsychotics on QTc and other ECG intervals/waves in three samples. Two discovery samples (cross-sectional sample n = 145 and prospective sample n = 68, naturalistic treatment) and a replication prospective sample (Clinical Antipsychotic Trials of Intervention Effectiveness, n = 515, randomized treatment) were analysed. In both prospective samples, baseline/follow-up changes in ECG parameters were analysed in relation to the number of psychotropic drugs stratified according to their known cardiovascular risk. In the cross-sectional sample, ECG parameters were compared among drugs with different risk profile. The possible effect of single nucleotide polymorphisms (SNPs) in the CACNA1C gene on QTc was also investigated. There was no evidence of mean QTc prolongation or increased risk of clinically relevant QTc prolongation (≥20 msec.) in association with psychotropic drugs stratified according to their known cardiovascular risk. The prescription of drugs with cardiovascular risk was less common in older individuals or individuals with cardiovascular comorbidities. Other factors (gender, baseline QTc, renal function) affected QTc. rs1006737 and SNPs in linkage disequilibrium with it modulated QTc duration/changes in all samples. An association between risk drugs and shorter RR interval or higher heart rate was found in all samples. A relevant effect of psychotropic drugs with cardiovascular risk on QTc duration was not observed. A number of factors other than psychotropic drugs may influence QTc. CACNA1C rs1006737 may modulate QTc in patients treated with psychotropic drugs.

Original languageEnglish
Pages (from-to)482-490
Number of pages9
JournalBasic and Clinical Pharmacology and Toxicology
Volume120
Issue number5
DOIs
Publication statusPublished - May 1 2017

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Psychotropic Drugs
Electrocardiography
Genes
Antipsychotic Agents
Antidepressive Agents
Single Nucleotide Polymorphism
Polymorphism
Nucleotides
Prescription Drugs
Linkage Disequilibrium
Pharmaceutical Preparations
Comorbidity
Heart Rate
Clinical Trials
Kidney
Therapeutics

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Electrocardiogram Alterations Associated With Psychotropic Drug Use and CACNA1C Gene Variants in Three Independent Samples. / Fabbri, Chiara; Boriani, Giuseppe; Diemberger, Igor; Filippi, Maria Giulia; Ravegnini, Gloria; Hrelia, Patrizia; Minarini, Alessandro; Albani, Diego; Forloni, Gianluigi; Angelini, Sabrina; Serretti, Alessandro.

In: Basic and Clinical Pharmacology and Toxicology, Vol. 120, No. 5, 01.05.2017, p. 482-490.

Research output: Contribution to journalArticle

Fabbri, C, Boriani, G, Diemberger, I, Filippi, MG, Ravegnini, G, Hrelia, P, Minarini, A, Albani, D, Forloni, G, Angelini, S & Serretti, A 2017, 'Electrocardiogram Alterations Associated With Psychotropic Drug Use and CACNA1C Gene Variants in Three Independent Samples', Basic and Clinical Pharmacology and Toxicology, vol. 120, no. 5, pp. 482-490. https://doi.org/10.1111/bcpt.12720
Fabbri, Chiara ; Boriani, Giuseppe ; Diemberger, Igor ; Filippi, Maria Giulia ; Ravegnini, Gloria ; Hrelia, Patrizia ; Minarini, Alessandro ; Albani, Diego ; Forloni, Gianluigi ; Angelini, Sabrina ; Serretti, Alessandro. / Electrocardiogram Alterations Associated With Psychotropic Drug Use and CACNA1C Gene Variants in Three Independent Samples. In: Basic and Clinical Pharmacology and Toxicology. 2017 ; Vol. 120, No. 5. pp. 482-490.
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