Use of tricyclic antidepressants as analgesic adjuvants results in nonhazardous prolongation of the QTc interval

Osaka City Med J. 2014 Jun;60(1):11-9.


Background: Tricyclic antidepressants (TCAs) are known to prolong QTc interval. However, little is known about the QTc lengthening effect of TCAs at analgesic dosages and the predictive factors for abnormal QTc prolongation.

Methods: We conducted a single-center, retrospective observational study, and evaluated 87 patients (65 amitriptyline, 22 nortriptyline) who underwent 12-lead electrocardiogram (ECG) examinations both before and after receiving TCAs for herpes zoster pain or postherpetic neuralgia from May 2007 to January 2012. Data on QTc interval, age, gender, the type and daily dosage of TCAs, the medication period until the second ECG examination, and ECG findings were obtained from electronic medical charts.

Results: The median daily dosages were 25 mg/day for amitriptyline and 10 mg/day for nortriptyline. The median medication period for all participants was 62 days. TCAs significantly prolonged the QTc interval (before, 413.2 +/-17.0 ms; after, 419.9 +/- 18.9 ms, p < 0.01). Three patients showed marked QTc prolongation, but it did not exceed 500 ms, or deltaQTc of 60 ms, and none had an episode of fatal arrhythmia. Univariate logistic regression analysis revealed left ventricular hypertrophy (LVH) to be the sole risk factor for abnormal QTc prolongation. The adjusted odds ratio was 4.09 (95% CI, 1.01-16.55, p < 0.05) by multivariate logistic regression analysis.

Conclusions: TCAs as analgesic adjuvant significantly prolonged the QTc interval, but within an acceptable range. LVH was a significant predictor of abnormal QTc prolongation.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amitriptyline / adverse effects*
  • Analgesics / adverse effects*
  • Antidepressive Agents, Tricyclic / adverse effects*
  • Electrocardiography
  • Female
  • Herpes Zoster / complications
  • Humans
  • Hypertrophy, Left Ventricular / complications
  • Japan
  • Logistic Models
  • Long QT Syndrome / chemically induced*
  • Long QT Syndrome / diagnosis
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neuralgia, Postherpetic / diagnosis
  • Neuralgia, Postherpetic / drug therapy*
  • Nortriptyline / adverse effects*
  • Odds Ratio
  • Pain Measurement
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors


  • Analgesics
  • Antidepressive Agents, Tricyclic
  • Amitriptyline
  • Nortriptyline