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SSRIs recommended for patients with CHD, depression
For almost half a century, an association between coronary heart disease and depression has been recognized.
It is estimated that up to 20% of patients hospitalized with an MI meet the criteria for major depression and even more have depressive symptoms. Prevalence is similar in patients hospitalized for HF, unstable angina and revascularization. Because depression in patients with CHD is associated with increased cardiovascular morbidity and mortality, early diagnosis and adequate treatment is essential in the overall management of patients with CHD. Depression in patients with CHD has been associated with poor compliance with cardiac rehabilitation programs as well as poor medication adherence. Therefore, in September 2008, the American Heart Association, with endorsement from the American Psychiatric Association, released a Science Advisory including recommendations for screening, referral and treatment of depression in patients with CHD.
Assessing depression
The AHA Science Advisory recommends use of the Patient Health Questionnaire to assess depressive symptomatology, which was developed by the MacArthur Initiative on Depression and Primary Care (depression-primarycare.org). In order to assess whether patients are currently depressed, the best first step is to administer the first two questions of the Patient Health Questionnaire (PHQ-2), which assess a patient’s level of interest in or pleasure derived from doing things, as well as whether they are feeling down, depressed or hopeless during the prior two weeks. If a response of either “more than half the days” or “nearly every day” is received for any of these questions, then the full Patient Health Questionnaire (PHQ-9) should be administered, which can usually be completed in less than five minutes while a patient is waiting to be seen for a clinic visit. After scoring, the PHQ-9 results can be used to determine a provisional depression diagnosis, including a treatment recommendation. The score guides treatment with antidepressants, psychotherapy or a combination of both.
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There are a number of observational trials evaluating the use of serotonin reuptake inhibitors (SSRIs) on cardiovascular morbidity and mortality in patients with heart disease. These trials have mixed results. There are only two published randomized controlled trials comparing an SSRI vs. placebo in patients with CHD and another in patients with chronic HF in abstract form only (see table online at CardiologyToday.com). While these three trials included relatively small numbers of patients and did not evaluate long-term CV outcomes, the two in patients with CHD provide evidence suggesting treatment of depressed patients with CHD with either sertraline or cetalopram is safe, and results in improved depressive symptoms, and as a result, both of these SSRIs are recommended as first line treatment in the AHA Science Advisory. The third study in patients with CHF did not show added benefit of sertraline over and above a nurse-facilitated supportive intervention. Patients who have SSRI therapy initiated should be closely monitored during the first two months for adverse outcomes, particularly symptoms of suicidal ideation.
Possible interactions
Of importance to note by cardiologists are potential drug interactions with SSRIs and drugs routinely used in patients with CHD. Because both sertraline (Zoloft, Pfizer) and citalopram (Celexa, Forest Laboratories) are mild inhibitors of CYP2D6, co-administration with drugs metabolized via the same pathway, including some beta-blockers (carvedilol [Coreg, GlaxoSmithKline], metoprolol, propranolol and timolol) and antiarrhythmics (encainide, flecainide, mexiletine [Mexitil, Boehringer Ingelheim] and propafenone), can result in increased concentrations. Because the clinical effects of these drug interactions will vary, close monitoring of patients taking SSRIs with these cardiovascular therapies is necessary.
Additionally, SSRIs may inhibit the serotonin uptake by platelets, which could augment the antiplatelet effects of aspirin and NSAIDs, and may enhance the effects of warfarin. Patients should be closely monitored for signs and symptoms of bleeding and in those patients on a stable dose of warfarin who have SSRI therapy initiated, close INR follow-up is necessary.
Patients with heart disease and depression who are stabilized on other SSRIs should continue them, although tricyclic antidepressants and monoamine oxidase inhibitors are generally contraindicated for treatment of depression in these patients due to their cardiotoxic adverse events.
Rhonda Cooper-DeHoff, Pharm D, MS, is Assistant Director of Clinical Programs and Research Assistant Professor, Division of Cardiology at University of Florida College of Medicine, Gainesville.
For more information:
- Lichtman JH, Bigger JT, Jr., Blumenthal JA, et al. Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association. Circulation. 2008;118:1768-1775.
- Glassman AH, O’Connor CM, Califf RM, et al. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA. 2002;288:701-709.
- Lesperance F, Frasure-Smith N, Koszycki D, et al. Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial. JAMA. 2007;297:367-379.
