BMJ 2001;323:666-669 ( 22 September )

Primary care

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

Julia Hippisley-Cox, senior lecturer in general practice, a Mike Pringle, professor of general practice, a Vicky Hammersley, research network coordinator, Trent Focus, a Nicola Crown, researcher, b Alison Wynn, researcher in general practice, a Andy Meal, lecturer, c Carol Coupland, senior lecturer in statistics. a

a Division of General Practice, University of Nottingham, Nottingham NG7 2RD, b Collingham Medical Centre, Collingham, Nottinghamshire NG23 7LB, c School of Nursing, Medical School, Queen's Medical Centre, Nottingham NG7 2UH

Correspondence to: Julia Hippisley-Cox julia.hippisley-cox{at}nottingham.ac.uk

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
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
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



© BMJ 2001
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Relevant Articles

Risk of adverse gastrointestinal outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis
Julia Hippisley-Cox, Carol Coupland, and Richard Logan
BMJ 2005 331: 1310-1316. [Abstract] [Full Text] [PDF]

Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis
Julia Hippisley-Cox and Carol Coupland
BMJ 2005 330: 1366. [Abstract] [Full Text] [PDF]

Dosulepin increases the risk of heart disease
BMJ 2001 323: 0. [Full Text]

This article has been cited by other articles:

  • Von Ruden, A. E., Adson, D. E., Kotlyar, M. (2008). Effect of Selective Serotonin Reuptake Inhibitors on Cardiovascular Morbidity and Mortality. J CARDIOVASC PHARMACOL THER 13: 32-40 [Abstract]  
  • de Jonge, P., Honig, A., van Melle, J. P., Schene, A. H., Kuyper, A. M.G., Tulner, D., Schins, A., Ormel, J., The MIND-IT Investigators, (2007). Nonresponse to Treatment for Depression Following Myocardial Infarction: Association With Subsequent Cardiac Events. Am. J. Psychiatry 164: 1371-1378 [Abstract] [Full text]  
  • Hippisley-Cox, J., Coupland, C., Logan, R. (2005). Risk of adverse gastrointestinal outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ 331: 1310-1316 [Abstract] [Full text]  
  • Hippisley-Cox, J., Coupland, C. (2005). Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ 330: 1366- [Abstract] [Full text]  
  • Tata, L J, West, J, Smith, C, Farrington, P, Card, T, Smeeth, L, Hubbard, R (2005). General population based study of the impact of tricyclic and selective serotonin reuptake inhibitor antidepressants on the risk of acute myocardial infarction. Heart 91: 465-471 [Abstract] [Full text]  
  • Marzari, C., Maggi, S., Manzato, E., Destro, C., Noale, M., Bianchi, D., Minicuci, N., Farchi, G., Baldereschi, M., Di Carlo, A., Crepaldi, G., the Italian Longitudinal Study on Aging Working Gr, (2005). Depressive Symptoms and Development of Coronary Heart Disease Events: The Italian Longitudinal Study on Aging. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 60: 85-92 [Abstract] [Full text]  
  • Rainone, F. (2004). Treating Adult Cancer Pain in Primary Care. J Am Board Fam Med 17: S48-S56 [Abstract] [Full text]  
  • Allonier, C, Chevalier, A, Zins, M, Catelinois, O, Consoli, S., Goldberg, M, Lahon, G (2004). Anxiety or depressive disorders and risk of ischaemic heart disease among French power company employees. Int J Epidemiol 33: 779-786 [Abstract] [Full text]  
  • Pringle, M. (2003). Improving quality: bridging the health sector divide. Int J Qual Health Care 15: 457-462 [Abstract] [Full text]  
  • Danner, M., Kasl, S. V., Abramson, J. L., Vaccarino, V. (2003). Association Between Depression and Elevated C-Reactive Protein. Psychosom. Med. 65: 347-356 [Abstract] [Full text]  
  • MacHale, S. (2002). Managing depression in physical illness. Adv. Psychiatr. Treat. 8: 297-305 [Full text]  

Rapid Responses:

Read all Rapid Responses

Are antidepressants an independant risk factor for ischaemic heart disease?
Peter Cansfield
bmj.com, 22 Sep 2001 [Full text]
Is dothiepin really different?
W P Plummer
bmj.com, 24 Sep 2001 [Full text]
Antidepressants and ischaemic heart disease
K F Ashley
bmj.com, 27 Sep 2001 [Full text]
Dothiepin and ischaemic heart disease
Joe Reilly
bmj.com, 30 Oct 2001 [Full text]
Depression not Dosulpin increases IHD
Alan Thomas
bmj.com, 30 Oct 2001 [Full text]
Doc2Doc Vacancy
Access jobs at BMJ Careers
Whats new online at Student BMJ