Antidepressant, Exercise Help Combat Anxiety in Coronary Heart Disease

Megan Brooks

August 27, 2021

For patients with stable coronary heart disease (CHD) who have high levels of anxiety, treatment with the antidepressant escitalopram (Lexapro) may help lower anxiety levels. Exercise can also be helpful, although its benefits with regard to anxiety are less consistent.

That's according to results from the single-site UNWIND (Understanding the Benefits of Exercise and Escitalopram in Anxious Patients With Coronary Heart Disease) randomized clinical trial.

"We hypothesized that both escitalopram and exercise would result in greater reductions in anxiety compared to placebo, so the findings were predicted and confirmed," James A. Blumenthal, PhD, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, told Medscape Medical News.

The results were published online August 18 in JAMA Psychiatry.

Clinically Meaningful Results

Anxiety is common in adults with CHD and is associated with poor health outcomes. However, effective treatment for anxiety in patients with CHD remains uncertain; few studies have examined the effects of treating anxiety in patients with cardiac disease.

The UNWIND trial tested the separate effects of the selective serotonin reuptake inhibitor escitalopram and aerobic exercise in comparison with placebo on anxiety and CHD biomarkers of risk in 128 adults (mean age, 64.6 years; 29% women) with stable CHD and moderate to severe levels of anxiety (baseline Hamilton Anxiety Rating Scale score, 15.9).

Fifty-two individuals were randomly allocated to participate in aerobic exercise three times per week for 35 minutes per session at an intensity of 70% to 85% of heart rate reserve for 12 weeks.

Fifty-three patients were randomly assigned to receive oral escitalopram for 12 weeks, starting at 5 mg daily and increasing to 20 mg daily by week 4. The remaining 23 participants took placebo pills for 12 weeks.

Scores on the Hospital Anxiety and Depression–Anxiety Subscale (HADS-A) after 12 weeks (primary outcome) indicated reduced levels of anxiety in all groups. The average reductions were -5.7 (95% CI, -6.4 to -5.0) in the escitalopram group, -4.0 (95% CI, -4.7 to -3.2) in the exercise group, and -3.5 (95% CI, -4.5 to -2.4) in the placebo group.

In a post hoc comparison, there were greater reductions in HADS-A scores in the escitalopram group than in the group that received placebo (P = .003). There were no significant differences between the exercise group and the placebo group (P = .69).

Escitalopram produced clinically meaningful reductions in anxiety, as well as significant reductions in depression, the investigators report.

Exercise Helpful in General

Although anxiety scores were lower in all groups after 12 weeks, Blumenthal said he was surprised that exercise did not yield better results than placebo.

"However, upon further reflection, the placebo group received more than just a pill. They met with the treating psychiatrist six times over the course of the 12 weeks and also received weekly phone calls from study staff to assess anxiety symptoms, all of which may have contributed to the improvement in symptoms," he said.

Blumenthal also noted that although participants in the exercise group reported less anxiety, the differences in the trait anxiety scores following the exercise and placebo conditions were not statistically significant.

Levels of state anxiety, which is how a person is feeling at a particular moment, were lower in the exercise group than in the placebo group after 12 weeks and were comparable to those of the escitalopram group.

The researchers found no consistent changes after the three interventions in the CHD biomarkers of heart rate variability, baroreflex sensitivity, and flow-mediated dilation.

However, the 12-week treatment period may have been too short to see changes in these biomarkers. Escitalopram reduced urinary catecholamine levels, indicative of a reduction in sympathetic nervous system activity, the investigators report.

"I think the clear message is that escitalopram is safe and effective for treating anxiety in patients with coronary heart disease," said Blumenthal.

Exercise "improves functional capacity and reduces risk for heart disease and lowers risk for premature death in patients with existing heart disease and has important mental health benefits. However, the presence of significant comorbid anxiety may attenuate some of those benefits," he noted.

"And it may take longer than 12 weeks to achieve the maximal benefits; so I would encourage people to stay with it. To achieve the most benefit from exercise, it must be sustained," Blumenthal added.

The study was funded by a grant from the National Heart, Lung, and Blood Institute. The investigators have disclosed no relevant financial relationships.

JAMA Psychiatry. Published online August 18, 2021. Abstract

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