Intended for healthcare professionals

Primary Care

Antidepressants as risk factor for ischaemic heart disease: case-control study in primary care

BMJ 2001; 323 doi: (Published 22 September 2001) Cite this as: BMJ 2001;323:666
  1. Julia Hippisley-Cox, senior lecturer in general practice (julia.hippisley-cox{at},
  2. Mike Pringle, professor of general practicea,
  3. Vicky Hammersley, research network coordinator, Trent Focusa,
  4. Nicola Crown, researcherb,
  5. Alison Wynn, researcher in general practicea,
  6. Andy Meal, lecturerc,
  7. Carol Coupland, senior lecturer in statisticsa
  1. a Division of General Practice, University of Nottingham, Nottingham NG7 2RD
  2. b Collingham Medical Centre, Collingham, Nottinghamshire NG23 7LB
  3. c School of Nursing, Medical School, Queen's Medical Centre, Nottingham NG7 2UH
  1. Correspondence to: Julia Hippisley-Cox
  • Accepted 13 June 2001


Objectives: To determine whether antidepressants are a risk factor for ischaemic heart disease and to compare the risk for different subgroups of antidepressants and individual antidepressants.

Design: Case-control study.

Setting: Nine general practices recruited from the Trent Focus Collaborative Research Network.

Participants: 933 men and women with ischaemic heart disease matched by age, sex, and practice to 5516 controls.

Main outcome measure: Adjusted odds ratio for ischaemic heart disease calculated by logistic regression.

Results: Odds ratios for ischaemic heart disease were significantly raised for patients who had ever received a prescription for tricyclic antidepressants even after diabetes, hypertension, smoking, body mass index, and use of selective serotonin reuptake inhibitors had been adjusted for (1.56; 95% confidence interval 1.18 to 2.05). Patients who had ever taken dosulepin (dothiepin) had a significantly raised odds ratio for ischaemic heart disease after adjustment for confounding factors and use of other antidepressants (1.67, 1.17 to 2.36). There was no significant increase in the odds ratios for amitriptyline, lofepramine, and selective serotonin reuptake inhibitors in multivariate analysis. Increasing maximum doses of dosulepin were associated with increasing odds ratios for ischaemic heart disease. Similarly, there was a significant positive trend associated with increasing numbers of prescriptions of dosulepin (adjusted odds ratio 1.52 for 1 prescription, 1.39 for 2-3, and 1.96 for ≥4, P<0.002).

Conclusion: There is good evidence for an association between dosulepin and subsequent ischaemic heart disease and for a dose-response relation.

What is already known on this topic

What is already known on this topic Over 45% of patients in hospital after myocardial infarction have depression

Depression is an independent risk factor for increased mortality and morbidity after myocardial infarction

What this study adds

What this study adds Patients who had ever taken dosulepin (dothiepin) had significantly increased risk of ischaemic heart disease after confounding factors had been adjusted for

The association followed a dose-response relation

The effect of other antidepressants was not significant after adjustment for confounders


  • Funding This project was supported by Culyer research and development funds.

  • Competing interests None declared.

  • Accepted 13 June 2001
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