title: Antipsychotic treatment is associated with risk of atrial fibrillation: A nationwide nested case-control study.
abstract: BACKGROUND
  Antipsychotic agents are well known for their arrhythmigenic effect on ventricular arrhythmia. Though a few case reports observed the occurrence of atrial fibrillation (AF) after antipsychotic exposure, information about their implication in AF is limited.
  
  
  METHODS
  Based on the National Health Insurance Database in Taiwan, we conducted a nested case-control study to investigate the relationship between antipsychotics and AF. From 2001 to 2010, a total of 34,053 cases of AF and 34,919 matched controls were enrolled. Antipsychotic exposure was measured and binding affinity to neurotransmitter receptors was calculated. Both medical and psychiatric comorbidities were identified and adjusted in multivariate logistic regression analysis.
  
  
  RESULTS
  Current antipsychotic use was associated with a 17% increased risk of AF relative to nonusers (adjusted OR: 1.17, 95% CI: 1.10-1.26). A dose-dependent relationship of antipsychotic exposure and AF risk was observed (P for trend <0.001). Antipsychotics with higher binding affinity to muscarinic M2 receptors were associated with a higher incidence of AF. In subgroup analysis, subjects with preexisting hypertension, diabetes, or coronary artery diseases were at greater risk of developing AF following antipsychotic exposure.
  
  
  CONCLUSIONS
  Antipsychotic exposure was associated with increased risk of AF, especially for agents with higher cardiac muscarinic receptor binding affinity. Physicians should monitor the occurrence of new-onset AF, and strictly control underlying medical risk factors while prescribing antipsychotic agents to high-risk populations.
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei, Taiwan; Cardiovascular Research Center, Taipei, Taiwan; Institute of Clinical Medicine, Taipei, Taiwan.
authors.forename: Ruey-Hsing
authors.initials: RH
authors.lastname: Chou
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei, Taiwan; Institute of Clinical Medicine, Taipei, Taiwan.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Lo
authors.affiliation: Department of Psychiatry, Taipei, Taiwan; Division of Psychiatry, School of Medicine, Taipei, Taiwan.
authors.forename: Ying-Jay
authors.initials: YJ
authors.lastname: Liou
authors.affiliation: Department of Nursing, Taipei, Taiwan.
authors.forename: Jiah-Hwang
authors.initials: JH
authors.lastname: Shu
authors.affiliation: Department of Nursing, Taipei, Taiwan.
authors.forename: Hsiu-Chuan
authors.initials: HC
authors.lastname: Hsu
authors.affiliation: Department of Nursing, Taipei, Taiwan.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Medical Research and Education, Taipei, Taiwan; Cardiovascular Research Center, Taipei, Taiwan.
authors.forename: Chin-Chou
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei, Taiwan; Cardiovascular Research Center, Taipei, Taiwan; Institute of Clinical Medicine, Taipei, Taiwan.
authors.forename: Po-Hsun
authors.initials: PH
authors.lastname: Huang
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei, Taiwan; Department of Medical Research and Education, Taipei, Taiwan; Cardiovascular Research Center, Taipei, Taiwan; Institute of Clinical Medicine, Taipei, Taiwan.
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei, Taiwan; Department of Medical Research and Education, Taipei, Taiwan; Cardiovascular Research Center, Taipei, Taiwan; Institute of Pharmacology National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jaw-Wen
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei, Taiwan; Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Wan-Leong
authors.initials: WL
authors.lastname: Chan
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei, Taiwan; Healthcare and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan; Cardiovascular Research Center, Taipei, Taiwan; Institute of Clinical Medicine, Taipei, Taiwan. Electronic address: hbleu@vghtpe.gov.tw.
authors.forename: Hsin-Bang
authors.initials: HB
authors.lastname: Leu
mesh_terms: D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000139:chemically induced* / Q000453:epidemiology* / Q000503:physiopathology; D016022:Case-Control Studies; D016001:Confidence Intervals; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012016:Reference Values; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D017678:Sex Distribution; D016019:Survival Analysis; D013624:Taiwan
chemical_list: D014150:Antipsychotic Agents
keywords: Antipsychotic agents; Atrial fibrillation; Autonomic dysfunction; Psychiatric diseases