Psychotherapy vs Pharmacotherapy for Depression in Heart Failure


Clinical trial compares outcomes with behavioral activation psychotherapy or antidepressant medication for depression in patients with heart failure.

heart failure


Data from a 1-year randomized trial showed that behavioral activation (BA) psychotherapy was comparable to antidepressant medication in relieving symptoms of depression in patients with heart failure.1 The psychotherapy group, however, demonstrated slightly more improvement in physical health-related quality of life (HRQOL), and had fewer emergency department (ED) visits and days of hospitalization.

“We postulated that the advantage of BA patients in improved physical-HRQOL, fewer ED visits and days of hospitalization might reflect the increased overall activation, motivation and self care as a result of BA,” lead study author Waguih IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, CA, told Psychiatric Times.

“The absence of antidepressant medication burden and/or increased enjoyable physical activity might be contributing factors with added benefits,” IsHak commented.

IsHak et al point out that approximately 50% of individuals with heart failure experience depressive symptoms, and that the severity of symptoms can be a greater risk factor for poor quality of life than the severity of their heart failure.2 Despite the American Heart Association recommending that patients with cardiovascular disease receive screening for depression,3 the symptoms often go undetected and untreated.

Noting concerns about the effectiveness of psychotherapy and the adverse effect burden of antidepressant medications, IsHak et al observed, "clinicians and patients lack evidence on which intervention to use for depression in heart failure."

To provide additional evidence to aid that determination, the investigators conducted a pragmatic, randomized comparative effectiveness trial of 2 therapeutic interventions: the evidence-based and manualized BA psychotherapy, and antidepressant medication treatment (MED). Both groups were treated within a health center collaborative care model for patients with heart failure, but without providing antidepressants to the BA group or psychotherapy to the MED group.

The investigators described BA therapy as emphasizing the improvement of patient mood, sense of control, and activity level through increased engagement in pleasurable and rewarding tasks; but without delving into complex cognitive domains to the extent undertaken with CBT. The investigators chose to use BA rather than cognitive behavioral therapy (CBT) for having comparable efficacy and being "more feasible in patients with HF."

"BA has lower implementation barriers due to high uptake by patients and feasibility of administration by various health care professionals with less expensive and lengthy training," IsHak et al explained.

The antidepressant regimens for the MED group were determined by the prescribers, but were to be consistent with American Psychological Association antidepressant guidelines and World Health Organization antidepressant equivalence dosing guidelines. The antidepressant selection by prescriber prerogative rather than a trial protocol, the investigators explained, allowed for individualized medication selection with consideration of adverse effects and drug-drug interactions.

The pragmatic design of the comparative effectiveness trial was consistent with the PRECIS-2 tool,4 to help ensure that results could be generalized to larger population. The PRECIS-2 tool includes several domains, and scores conformance of the trial design with each. In the domain of participant eligibility, for example, PRECIS-2 poses: “To what extent are the participants in the trial similar to those who would receive this intervention if it was part of usual care.”

Comparing Outcomes

The BA and MED groups, with 208 participants in each, had no significant differences in demographic characteristics, or in the baseline severity of depressive symptoms as measured on the Patient Health Questionnaire 9-item (PHQ-9). Among the 78 caregivers enrolled, there was also no significant difference in baseline score on the 26-item Caregiver Burden Questionnaire for Heart Failure (CBQ-HF).

At 6 months, depressive symptom severity was reduced by approximately 50% in both groups. The reduction in PHQ-9 for BA group was 7.53 (SD 5.74); and 8.09 (SD 6.06) for the MED group. Both groups also demonstrated clinically significant improvement in secondary outcome measures of the physical- and mental-HRQOL, and the heart failure-specific QOL.

At 6 months, but not at the 3- and 12-month assessments, the BA group demonstrated statistically significantly better scores than the MED group on the physical- and HF- specific HRQOL. At 3, 6, and 12 months, the BA group had statistically significantly fewer ED visits as well as fewer days of hospitalization. There were no significant differences between groups in hospital readmissions or in mortality.

Although the trial was designed to compare the different interventions, IsHak considered the question of whether he might expect better outcomes if some components of the BA psychotherapy could be provided along with medication.

“It is hard to tell if some BA components hand-in-hand would work as well, without doing an actual comparative effectiveness study using this proposed third arm,” IsHak indicated. “However, we know from the research on full collaborative care that utilizing BA components with antidepressants is superior to usual care in depression. We just would not know until a study is actually performed if it would be as effective as BA for patients with heart failure.”

In a statementreleased by Cedars-Sinai on the publication of the trial report, IsHak emphasized that the findings support treatment options for depression in patients with heart failure.5

“The most important finding here is that patients experiencing depression have a choice in terms of their treatment between therapy or medications. Patients who prefer not to be on medication can do behavioral activation therapy with similar results,” IsHak said.

Dr Bender reports on medical innovations and advances in practice and edits presentations for news and professional education publications. He previously taught and mentored pharmacy and medical students, and he provided and managed pharmacy care and drug information services.


1. IsHak WW, Hamilton MA, Korouri S, et al. Comparative effectiveness of psychotherapy vs antidepressants for depression in heart failure. JAMA Netw Open. 2024;7(1):e23529094.

2. Müller-Tasch T, Peters-Klimm F, Schellberg D, et al. Depression is a major determinant of quality of life in patients with chronic systolic heart failure in general practice. J Card Fail. 2007;13(10):818-824.

3. Lichtman JH, Bigger JT Jr, Blumenthal JA, et al; American Heart Association Prevention Committee of the Council on Cardiovascular Nursing; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Epidemiology and Prevention; American Heart Association Interdisciplinary Council on Quality of Care and Outcomes Research; American Psychiatric Association. 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(17):1768-1775.

4. Loudon K, Treweek S, Sullivan F, et al. The PRECIS-2 tool: designing trials that are fit for purpose. BMJ. 2015;350:h2147.

5. Cedars-Sinai. Therapy versus medication: comparing treatments for depression in heart disease. Press release. ScienceDaily. January 17, 2024. Accessed February 5, 2024.

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