title: Electrocardiogram Alterations Associated With Psychotropic Drug Use and CACNA1C Gene Variants in Three Independent Samples.
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.
authors.affiliation: Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fabbri
authors.affiliation: Department of Cardiology, Modena University Hospital, University of Modena and Reggio Emilia, Modena MO, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Boriani
authors.affiliation: Department of Specialist, Diagnostic and Experimental Medicine, University of Bologna, Bologna, Italy.
authors.forename: Igor
authors.initials: I
authors.lastname: Diemberger
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Filippi
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Ravegnini
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Hrelia
authors.affiliation: Department of Diagnostic, Clinical and Public Health Medicine, Section of Psychiatry, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Minarini
authors.affiliation: IRCCS - Institute for Pharmacological Research "Mario Negri", Milan, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Albani
authors.affiliation: IRCCS - Institute for Pharmacological Research "Mario Negri", Milan, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Angelini
authors.affiliation: Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000209:etiology; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D014644:Genetic Variation; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000209:etiology / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type