Psychological and pharmacological interventions for depression in patients with coronary artery disease

Phillip J Tully, Ser Yee Ang, Emily Jl Lee, Eileen Bendig, Natalie Bauereiß, Jürgen Bengel, Harald Baumeister, Phillip J Tully, Ser Yee Ang, Emily Jl Lee, Eileen Bendig, Natalie Bauereiß, Jürgen Bengel, Harald Baumeister

Abstract

Background: Depression occurs frequently in individuals with coronary artery disease (CAD) and is associated with a poor prognosis.

Objectives: To determine the effects of psychological and pharmacological interventions for depression in CAD patients with comorbid depression.

Search methods: We searched the CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL databases up to August 2020. We also searched three clinical trials registers in September 2021. We examined reference lists of included randomised controlled trials (RCTs) and contacted primary authors. We applied no language restrictions.

Selection criteria: We included RCTs investigating psychological and pharmacological interventions for depression in adults with CAD and comorbid depression. Our primary outcomes included depression, mortality, and cardiac events. Secondary outcomes were healthcare costs and utilisation, health-related quality of life, cardiovascular vital signs, biomarkers of platelet activation, electrocardiogram wave parameters, non-cardiac adverse events, and pharmacological side effects.

Data collection and analysis: Two review authors independently examined the identified papers for inclusion and extracted data from the included studies. We performed random-effects model meta-analyses to compute overall estimates of treatment outcomes.

Main results: Thirty-seven trials fulfilled our inclusion criteria. Psychological interventions may result in a reduction in end-of-treatment depression symptoms compared to controls (standardised mean difference (SMD) -0.55, 95% confidence interval (CI) -0.92 to -0.19, I2 = 88%; low certainty evidence; 10 trials; n = 1226). No effect was evident on medium-term depression symptoms one to six months after the end of treatment (SMD -0.20, 95% CI -0.42 to 0.01, I2 = 69%; 7 trials; n = 2654). The evidence for long-term depression symptoms and depression response was sparse for this comparison. There is low certainty evidence that psychological interventions may result in little to no difference in end-of-treatment depression remission (odds ratio (OR) 2.02, 95% CI 0.78 to 5.19, I2 = 87%; low certainty evidence; 3 trials; n = 862). Based on one to two trials per outcome, no beneficial effects on mortality and cardiac events of psychological interventions versus control were consistently found. The evidence was very uncertain for end-of-treatment effects on all-cause mortality, and data were not reported for end-of-treatment cardiovascular mortality and occurrence of myocardial infarction for this comparison. In the trials examining a head-to-head comparison of varying psychological interventions or clinical management, the evidence regarding the effect on end-of-treatment depression symptoms is very uncertain for: cognitive behavioural therapy compared to supportive stress management; behaviour therapy compared to person-centred therapy; cognitive behavioural therapy and well-being therapy compared to clinical management. There is low certainty evidence from one trial that cognitive behavioural therapy may result in little to no difference in end-of-treatment depression remission compared to supportive stress management (OR 1.81, 95% CI 0.73 to 4.50; low certainty evidence; n = 83). Based on one to two trials per outcome, no beneficial effects on depression remission, depression response, mortality rates, and cardiac events were consistently found in head-to-head comparisons between psychological interventions or clinical management. The review suggests that pharmacological intervention may have a large effect on end-of-treatment depression symptoms (SMD -0.83, 95% CI -1.33 to -0.32, I2 = 90%; low certainty evidence; 8 trials; n = 750). Pharmacological interventions probably result in a moderate to large increase in depression remission (OR 2.06, 95% CI 1.47 to 2.89, I2 = 0%; moderate certainty evidence; 4 trials; n = 646). We found an effect favouring pharmacological intervention versus placebo on depression response at the end of treatment, though strength of evidence was not rated (OR 2.73, 95% CI 1.65 to 4.54, I2 = 62%; 5 trials; n = 891). Based on one to four trials per outcome, no beneficial effects regarding mortality and cardiac events were consistently found for pharmacological versus placebo trials, and the evidence was very uncertain for end-of-treatment effects on all-cause mortality and myocardial infarction. In the trials examining a head-to-head comparison of varying pharmacological agents, the evidence was very uncertain for end-of-treatment effects on depression symptoms. The evidence regarding the effects of different pharmacological agents on depression symptoms at end of treatment is very uncertain for: simvastatin versus atorvastatin; paroxetine versus fluoxetine; and escitalopram versus Bu Xin Qi. No trials were eligible for the comparison of a psychological intervention with a pharmacological intervention.

Authors' conclusions: In individuals with CAD and depression, there is low certainty evidence that psychological intervention may result in a reduction in depression symptoms at the end of treatment. There was also low certainty evidence that pharmacological interventions may result in a large reduction of depression symptoms at the end of treatment. Moderate certainty evidence suggests that pharmacological intervention probably results in a moderate to large increase in depression remission at the end of treatment. Evidence on maintenance effects and the durability of these short-term findings is still missing. The evidence for our primary and secondary outcomes, apart from depression symptoms at end of treatment, is still sparse due to the low number of trials per outcome and the heterogeneity of examined populations and interventions. As psychological and pharmacological interventions can seemingly have a large to only a small or no effect on depression, there is a need for research focusing on extracting those approaches able to substantially improve depression in individuals with CAD and depression.

Trial registration: ClinicalTrials.gov NCT00998400 NCT04986969 NCT04799899 NCT04529148.

Conflict of interest statement

Phillip Tully: Dr Tully reports receiving salary from the National Health and Medical Research Council of Australia. Dr Tully reports receiving salary and his institution received grant payment from the Alzheimer's Drug Discovery Foundation. Dr Tully has received royalties from Springer and Lambert Academic Publishing. Dr Tully reports receiving payment for development of educational presentations from the Mental Health Professionals Network. Dr Tully reports receiving payment for editorial services from Elsevier.

Ser Yee Ang: none to declare.

Emily JL Lee: none to declare.

Eileen Bendig: EB is an author of an included study, but was not involved in the data extraction or ratings of bias or quality for that study.

Natalie Bauereiss: NB is an author of an included study, but was not involved in the data extraction or ratings of bias or quality for that study.

Jürgen Bengel: JB is an author of an included study, but was not involved in the data extraction or ratings of bias or quality for that study.

Harald Baumeister: HB is an author of an included study, but was not involved in the data extraction or ratings of bias or quality for that study.