title: Increase of Heart Rate and QTc by Amitriptyline, But Not by Venlafaxine, Is Correlated to Serum Concentration.
abstract: Electrocardiographic pathologies are a common problem during antidepressant treatment. The authors investigated the association of serum concentrations of antidepressants and heart rate, QT, and QTc. Polymorphisms of NOS1AP (nitric oxide synthase 1 adaptor protein) rs10494366 and rs12143842 as potential influence factors also were considered. In the amitriptyline sample (n = 59), significant Spearman ρ correlations were found between serum concentration and QTc (r = 0.333, P = 0.010), as well as heart rate (r = 0.407, P = 0.001). Patients with a serum concentration greater than the therapeutic range (>200 ng/mL) exhibit significantly higher heart rates (87.0 ± 13.3 vs 80.0 ± 13.9, U test P = 0.011) and higher QTc values (443.8 ± 28.8 vs 427.9 ± 20.6, U test P = 0.022). Excluding the 26 patients with a serum concentration greater than the therapeutic range, patients with rs12143842 risk alleles exhibit higher heart rates and as a trend lower QT intervals with no difference in QTc. In the venlafaxine sample (n = 81), no significant association between serum concentration and heart rate, QT, or QTc was revealed. In summary, the risk for relevant electrocardiographic alterations induced by tricyclic antidepressants, such as amitriptyline, is dependent on serum concentrations. NOS1AP polymorphisms may be a genetic vulnerability factor.
authors.affiliation: From the *Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg; †Clinic of Psychiatry and Psychotherapy, Weißer Hirsch, Dresden; and ‡Department of Psychiatry, Psychosomatics and Psychotherapy, Johann Wolfgang Goethe University Frankfurt, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Unterecker
authors.forename: Bruno
authors.initials: B
authors.lastname: Pfuhlmann
authors.forename: Juliane
authors.initials: J
authors.lastname: Kopf
authors.forename: Sarah
authors.initials: S
authors.lastname: Kittel-Schneider
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000639:Amitriptyline / Q000009:adverse effects / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000494:pharmacology; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008133:Long QT Syndrome / Q000097:blood* / Q000139:chemically induced* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D000069470:Venlafaxine Hydrochloride / Q000009:adverse effects / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; C488081:NOS1AP protein, human; D000639:Amitriptyline; D000069470:Venlafaxine Hydrochloride