Highlights
- •Depression and antidepressant use have been associated with an increased risk of cardiovascular events and mortality.
- •This longitudinal study confirmed that exposure to depression and antidepressants increases the risk of cardiovascular events and death over 12 years.
- •Depression and antidepressants interact to modulate the risk of cardiovascular events and death, so that the risk seems greatest for older men with untreated depression and for those on antidepressants but with no depression.
- •Antidepressant treatment decreases the risk of cardiovascular morbidity and mortality among older men with depression, but not those without.
Abstract
Introduction
It is uncertain whether depression and exposure to antidepressants increase the risk
of cardiovascular events in later life. This study attempts to clarify whether the
risk of cardiovascular events associated with exposure to antidepressant medications
varies according to history of depression.
Methods
Cohort study of 5522 Australian men aged 70–89 years living in the metropolitan region
of Perth, Western Australia, who were followed for novel cardiovascular events over
12 years. Clinical diagnoses followed the International Classification of Diseases
(ICD) codes for ischaemic heart disease, cerebrovascular events and depressive disorders.
Participants self-reported their use of medications. Other study measures included
age, schooling, smoking history and the following concurrent morbidities: diabetes,
hypertension, cancer, dementia, and respiratory diseases, gastrointestinal and renal
diseases.
Results
374 men (6.8%) had a recorded or current diagnosis of depression and 365 (6.6%) were
using an antidepressant. Prevalent depression and antidepressant use were associated
with increased mortality hazard, but not the interaction between them (hazard ratio,
HR = 0.46, 95%CI = 0.33, 0.65). Depression (HR = 1.50, 95%CI = 1.21, 1.86) and antidepressants
(HR = 1.52, 95%CI = 1.20, 1.93) were associated with an increased risk of cardiovascular
events, but the interaction term was associated with decreased risk (HR = 0.51, 95%CI = 0.30,
0.87). All analyses were adjusted for other study measures.
Discussion
Depression and antidepressant use were associated with an increase in the 12-year
risk of cardiovascular events, while antidepressants were associated with a decrease
in the risk of cardiovascular events among older men with depression, but not among
those without. This suggests that the effect of this interaction on the risk of cardiovascular
events may be driven by the ability of antidepressants to lead to clinical improvements
in mood.
Keywords
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References
- Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015.Lancet. 2016; 388: 1659-1724
- Depression, antidepressant use and mortality in later life: the health in men study.PLoS One. 2010; 5e11266
- The contribution of major depression to the global burden of ischemic heart disease: a comparative risk assessment.BMC Med. 2013; 11: 250
- Depression and risk of stroke morbidity and mortality: a meta-analysis and systematic review.JAMA. 2011; 306: 1241-1249
- Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016: a systematic analysis for the Global Burden of Disease Study 2016.Lancet. 2017; 390: 1151-1210
- Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.Lancet. 2018; 391: 1357-1366
- Review of maintenance trials for major depressive disorder: a 25-year perspective from the US Food and Drug Administration.J. Clin. Psychiatry. 2014; 75: 205-214
- Effectiveness and cost-effectiveness of mindfulness-based cognitive therapy compared with maintenance antidepressant treatment in the prevention of depressive relapse or recurrence (PREVENT): a randomised controlled trial.Lancet. 2015; 386: 63-73
- Antidepressant use and risk of adverse outcomes in older people: population based cohort study.BMJ. 2011; 343: d4551
- Psychotropic medication use in Australia, 2007 to 2015: changes in annual incidence, prevalence and treatment exposure.Aust. N. Z. J. Psychiatry. 2017; 51: 990-999
- Depression treatment and 1-year mortality after acute myocardial infarction: insights from the TRIUMPH registry (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients’ Health Status).Circulation. 2017; 135: 1681-1689
- Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders.BMC Psychiatry. 2014; 14: S1
- Prevention and treatment of low back pain: evidence, challenges, and promising directions.Lancet. 2018; 391: 2368-2383
- Trends in psychotropic dispensing among older adults with dementia living in long-term care facilities: 2004-2013.Am. J. Geriatr. Psychiatry. 2015; 23: 1259-1269
- Australia’s Health.Australian Institute of Health and Welfare, Canberra2018 (16. AUS 221 16. AUS 221.2018)
- Cohort profile: the health in men study (HIMS).Int. J. Epidemiol. 2009; 38: 48-52
- A decade of data linkage in Western Australia: strategic design, applications and benefits of the WA data linkage system.Aust. Health Rev. 2008; 32: 766-777
- Short versions of the geriatric depression scale: a study of their validity for the diagnosis of a major depressive episode according to ICD-10 and DSM-IV.Int. J. Geriatr. Psychiatry. 1999; 14: 858-865
- Multiplicative models and cohort analysis.J. Am. Stat. Assoc. 1983; 78: 1-12
- Sensitivity analysis in observational research: introducing the E-value.Ann. Intern. Med. 2017; 167: 268-274
- Treatment of functional chest pain with antidepressants: a meta-analysis.Pain Phys. 2012; 15: E131-142
- Pregnancy, delivery, and neonatal complications in a population cohort of women with schizophrenia and major affective disorders.Am. J. Psychiatry. 2005; 162: 79-91
- Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration.PLoS Med. 2008; 5: e45
- The benefits of aspirin in early secondary stroke prevention.Lancet. 2016; 388: 312-314
- Depression and coronary heart disease.Nat. Rev. Cardiol. 2017; 14: 145-155
- Cardiovascular adverse reactions during antidepressant treatment: a drug surveillance report of German-speaking countries between 1993 and 2010.Int. J. Neuropsychopharmacol. 2014; 18
- Depression and cardiovascular disease.Prog. Cardiovasc. Dis. 2013; 55: 511-523
- Effects of selective serotonin reuptake inhibitors on platelet function: mechanisms, clinical outcomes and implications for use in elderly patients.Drugs Aging. 2011; 28: 345-367
- Platelet and endothelial activity in comorbid major depression and coronary artery disease patients treated with citalopram: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy Trial (CREATE) biomarker sub-study.J. Thromb. Thrombolysis. 2009; 27: 48-56
- Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial.Lancet. 2019; 393: 265-274
- Treatment indications for antidepressants prescribed in primary care in Quebec, Canada, 2006-2015.JAMA. 2016; 315: 2230-2232
- Anxiety and new onset of cardiovascular disease: critical review and meta-analysis.Br. J. Psychiatry. 2016; 208: 223-231
- Antidepressant medication use and future risk of cardiovascular disease: the Scottish Health Survey.Eur. Heart J. 2011; 32: 437-442
- Use of antidepressants and the risk of cardiovascular and cerebrovascular disease: a meta-analysis of observational studies.Eur. J. Clin. Pharmacol. 2017; 73: 487-497
- Antidepressant use and risk of coronary heart disease: meta-analysis of observational studies.Br. J. Clin. Pharmacol. 2014; 78: 727-737
- Generalized anxiety disorder in late life: lifetime course and comorbidity with major depressive disorder.Am. J. Geriatr. Psychiatry. 2005; 13: 77-80
Article info
Publication history
Published online: June 28, 2019
Accepted:
June 27,
2019
Received in revised form:
June 24,
2019
Received:
May 30,
2019
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
