Treating Depression May Improve Long-Term Cardiac Outcomes

Jae-Min Kim, MD, PhD

Patients with depression following acute coronary syndrome (ACS) saw a lower risk of major adverse cardiac events (MACE) years later after taking the selective serotonin reuptake inhibitor (SSRI) escitalopram, new research shows.

The study by a team at Chonnam National University Medical School in Gwangju, South Korea, followed a total of 300 patients with recent acute coronary syndrome and depression. The participants took either escitalopram (Lexapro) or a placebo for a 24-week treatment period. They completed a median 8.1 years of follow-up.

Researchers, led by Jae-Min Kim, MD, PhD, Department of Psychiatry, Chonnam National University Medical School, found that major cardiac events occurred in 40.9% of the participants who took escitalopram compared to 53.6% of those who received the placebo.

“Escitalopram treatment for depression following ACS has a beneficial effect on long-term cardiac outcomes,” Kim told MD Magazine®.

Depression is frequently comorbid with acute coronary syndrome and is associated with poor outcomes ranging from nonfatal events to increased mortality.

However, Kim and colleagues wrote in JAMA, the Journal of the American Medical Association, the associations between anti-depressant treatment and long-term cardiac outcomes have been inconclusive. In particular, previous research has been limited by short time periods, they said.

“This study aimed to investigate whether the effect of escitalopram versus placebo for treating acute-phase depression in patients with recent ACS resulted in benefits in longer-term cardiac outcomes,” the authors wrote.

To investigate, the team considered data on 181 men and 119 women with a median age of 60 in a randomized, double-blind, placebo-controlled trial from May 2007 to March 2013. The patient follow-up was completed in June 2017.

Patients initially received a 10-mg daily dose of escitalopram, which could be adjusted from 5 mg per day to 20 mg per day based on a clinical decision by investigators.

The team then assessed the patients on the components of MACE: myocardial infarction; cardiac death; all-cause mortality; and percutaneous coronary intervention. They found that the incidence of myocardial infarction was significantly lower in the escitalopram group at 8.7% versus 15.2% for the placebo group. There were no significant differences in the other MACE components.

Incidence rates for all-cause mortality were 20.8% in escitalopram takers compared to 24.5% for the placebo group. Cardiac death was 10.7% versus 13.2% respectively. Percutaneous coronary intervention was 12.8% compared to 19.9%.

Kim said 2 possible mechanisms may be at play influencing the decreased incidence of myocardial infarction among the escitalopram group.

“First, improvement of depression may promote health behavior including better treatment adherence, more regular hospital visits or medication, more adjusted exercise or diet,” he said.

Second, he added, “escitalopram may positively affect common biomarkers for ACS and depression including brain derived neurotrophic factor and pro-inflammatory cytokines; and may normalize autonomic and platelet dysfunction, which have adverse effects on cardiac outcomes.”

Asked about why the team chose to investigate escitalopram, Kim said that the drug has been known to be more effective and safer than another SSRI, citalopram (Celexa).

“There has been a concern raised by US Food and Drug Administration (FDA) about the use of higher doses of citalopram in relation to QTc prolongation, a surrogate marker of cardiotoxicity,” Kim said. In addition, citalopram’s longer-term follow-up results have not yet been published, he said.

Kim said that further research into psychosocial factors including depression comorbidity and treatment interactions on long-term cardiac outcomes is important.

“Appropriate treatment of depression from the acute stage of ACS could improve long-term treatment outcomes of ACS itself,” he said.