The heart of depression: Treating patients who have cardiovascular disease
- Studies of SSRIs have shown them to be safe and well tolerated in post-MI patients. Because Mrs. T failed only 1 previous SSRI trial (sertraline), it would be reasonable to select an alternate agent within this class.
- An FDA alert highlights the risk of using clopidogrel in combination with drugs such as omeprazole, ketoconazole, fluoxetine, and fluvoxamine.10 These medications are CYP2C19 inhibitors, which can reduce clopidogrel’s effect by inhibiting conversion of the parent drug to its active metabolite.
- Adding a strong CYP2D6 inhibitor, such as fluoxetine or paroxetine, could increase the effects of metoprolol, which is a CYP2D6 substrate.11
Cardiac outcomes
Evidence is insufficient to ascertain whether pharmacologic management of depression can reduce the risk of future cardiac events. Data evaluating SSRIs’ effects on cardiac outcomes are equivocal5,12,13 and limited by inadequate power.14,15 Preliminary evidence suggests patients who respond to antidepressant treatment may have improved cardiovascular outcomes.16,17 Evidence obtained from the Sertraline Antidepressant Heart Attack Randomized Trial (SADHART), the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) trial, and the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial suggest the SSRIs sertraline and citalopram can be used safely, with minimal bleeding risk, to treat depression in CVD patients (Table 2).14,15,18 When treating depressed patients who have CVD, remember to include nonpharmacologic options, such as psychotherapy, in the treatment plan, although studies have not yet shown improved cardiovascular mortality rates in patients receiving CBT.8,17,18
Although other SSRIs may be helpful for Mrs. T, citalopram is one of the best-studied agents post-MI, with the CREATE study supporting its efficacy and tolerability in this population. Citalopram has negligible drug interactions, although it is a weak inhibitor of CYP2D6 and the possibility of increasing metoprolol’s effects should be monitored. All SSRIs are associated with an increased risk of bleeding in patients receiving antiplatelet therapy; however, in Mrs. T’s case the risks are minimal, which makes citalopram a reasonable option. CBT also could be resumed to optimize Mrs. T’s treatment.
Table 2
SSRIs and cardiovascular disease: Results from RCTs
| Study | Design | Results |
|---|---|---|
| SADHART14 | Randomized, double-blind trial of sertraline vs placebo for 24 weeks for depression following MI or unstable angina (N=369) | Sertraline was more effective than placebo as measured by CGI-I, but not HAM-D in the total sample; both measures demonstrated statistical significance in patients with a history of MDD and those with HAM-D score >18 with 2 past episodes of MDD; incidence of severe cardiovascular events was 14.5% with sertraline and 22.4% with placebo (P=NS) |
| ENRICHD18 | Randomized, double-blind, controlled trial of early CBT supplemented with SSRI (usually sertraline) if necessary vs usual care for depression and low perceived social support after MI (N=2,481) | Intervention had a modest effect on depressive symptoms; antidepressant use reduced the risk of death or nonfatal MI |
| CREATE15 | Randomized, controlled, 12-week, parallel-group trial of 284 depressed patients with coronary artery disease first randomized to weekly interpersonal psychotherapy for 12 weeks plus clinical management or clinical management only, then randomized to citalopram or placebo for 12 weeks | Although the effect size was small, citalopram was more effective for depression than placebo and did not differ in effect on cardiac parameters, such as blood pressure, heart rate, or ECG change (P=.005) |
| CBT: cognitive-behavioral therapy; CGI-I: Clinical Global Impressions-Improvement scale; CREATE: Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy; ENRICHD: Enhancing Recovery in Coronary Heart Disease Patients; HAM-D: Hamilton Depression Rating Scale; MDD: major depressive disorder; MI: myocardial infarction; NS: nonsignificant; RCT: randomized controlled trial; SADHART: Sertraline Antidepressant Heart Attack Randomized Trial; SSRI: selective serotonin reuptake inhibitor | ||
- Summers KM, Martin KE, Watson K. Impact and clinical management of depression in patients with coronary artery disease. Pharmacotherapy. 2010;30:304-322.
- Indiana University School of Medicine. P450 drug interaction table. Indiana University School of Medicine. https://medicine.iupui.edu/clinpharm/ddis/table.asp.
Drug Brand Names
- Bupropion • Wellbutrin, Zyban
- Citalopram • Celexa
- Clopidogrel • Plavix
- Desipramine • Norpramin
- Duloxetine • Cymbalta
- Fluoxetine • Prozac
- Fluvoxamine • Luvox
- Ketoconazole • Nizoral
- Lisinopril • Prinivil, Zestril
- Metoprolol • Lopressor, Toprol
- Mirtazapine • Remeron
- Omeprazole • Prilosec
- Paroxetine • Paxil
- Sertraline • Zoloft
- Simvastatin • Zocor
- Trazodone • Desyrel
Disclosure
Dr. Bostwick reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
