By John Hughes, PhD, FAACVPR Department of Psychological Sciences, Kent State University | May 9, 2019

Many patients with COPD who enroll in pulmonary rehabilitation (PR) are depressed. Depression in COPD increases risk of acute exacerbations[i] and mortality.[ii]^,[iii],[iv] It is typical to screen for depression at enrollment in PR, and patients with elevated scores should undergo further evaluation to determine whether or not intervention is appropriate.

The main options for addressing depression are behavioral and pharmacological therapies. Unfortunately, the infrastructure to provide cognitive behavioral therapy for depression in PR is often lacking, and developing sufficient community referral sources is not an easy task. Thus, many patients are referred to their primary care physician (or another physician) to be evaluated for antidepressants.

Do antidepressants work for patients enrolled in pulmonary rehabilitation who have COPD? The 2019 Report of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) says simply “there is no evidence that anxiety and depression should be treated differently in the presence of COPD”[v] (p. 133). That may be true, because there is not much evidence on the effectiveness of antidepressants in patients with COPD.

• A recent Cochrane review[vi] found only four randomized clinical trials (RCT’s) comparing antidepressants with placebo in patients with COPD. Three tested selective serotonin reuptake inhibitors (SSRI’s), the most widely used class of antidepressants. The pooled analysis found no benefit of SSRI’s for depression or quality of life for patients with COPD. However, two trials did report improvement in exercise tolerance. Thus, the number of studies and quality of evidence that antidepressants work for patients with COPD is insufficient.
• On the other hand, patients enrolled in PR are already receiving a multi-component intervention that can affect depression. Adding antidepressants results in something called “multiple treatment interference,”[vii] which means that it is not possible to attribute improvement in depression to specifically the antidepressant or the effects of pulmonary rehabilitation. Given this methodological challenge, there may never be a randomized clinical trial of antidepressants for patients with COPD who are currently enrolled in PR. Nevertheless, if SSRI’s possibly improve exercise tolerance, they might help patients receive the full benefit of supervised exercise.
• Furthermore, one reason clinical trials of antidepressants are disappointing is because depression scores typically improve quickly for both patients on the active drug and the placebo. A lot of the improvement in depression in drug trials appears to be due to the patient taking action to address their depression, including the expectation that they will improve. Enrollment in PR should also harness the power of positive expectations and a problem-solving focus in patients with comorbid COPD and depression.
• Finally, in real-world clinical practice, only about 1/3 of depressed patients with COPD receive treatment with antidepressants.[viii] This may be by choice. Often, these patients do not prefer pharmacological treatment of depression.[ix]

In conclusion, the evidence that antidepressants medication can address depression in PR patients with comorbid COPD and depression is neither abundant nor strong. Whether or not patients want to add an antidepressant is ultimately a personal choice the patient makes with their physician. Nevertheless, PR staff should rest assured that exercise-based PR is beneficial for depression,[x]^,[xi],[xii] whether or not patients take antidepressants. Because PR is severely under-utilized, with less than 4% of eligible patients participating,[xiii] enrolling patients in PR is a promising approach to addressing depression and improving quality of life in patients with COPD.

[i] Xu W, Collet J-P, Shapiro S, et al. Independent effect of depression and anxiety on chronic obstructive pulmonary disease exacerbations and hospitalizations. American journal of respiratory and critical care medicine. 2008;178(9):913-920.
[ii] Qian J, Simoni-Wastila L, Rattinger GB, et al. Associations of depression diagnosis and antidepressant treatment with mortality among young and disabled Medicare beneficiaries with COPD. General hospital psychiatry. 2013;35(6):612-618.
[iii] de Voogd JN, Wempe JB, Koëter GH, et al. Depressive symptoms as predictors of mortality in patients with COPD. Chest. 2009;135(3):619-625.
[iv] Cuijpers P, Vogelzangs N, Twisk J, Kleiboer A, Li J, Penninx BW. Comprehensive meta-analysis of excess mortality in depression in the general community versus patients with specific illnesses. American journal of psychiatry. 2014;171(4):453-462.
[v] https://goldcopd.org/gold-reports/
[vi] Pollok J, van Agteren JEM, Carson-Chahhoud KV. Pharmacological interventions for the treatment of depression in chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2018, Issue 12. Art. No.: CD012346. DOI: 10.1002/14651858.CD012346.pub2.www.cochranelibrary.com
[vii] Shapiro, E. S., Kazdin, A. E., & McGonigle, J. J. (1982). Multiple-treatment interference in the simultaneous-or alternating-treatments design. Behavioral Assessment.
[viii] Matte DL, Pizzichini MM, Hoepers AT, et al. Prevalence of depression in COPD: a systematic review and meta-analysis of controlled studies. Respiratory medicine. 2016;117:154-161
[ix] Xu W, Collet J-P, Shapiro S, et al. Independent effect of depression and anxiety on chronic obstructive pulmonary disease exacerbations and hospitalizations. American journal of respiratory and critical care medicine. 2008;178(9):913-920.
[x] Nishi SP, Zhang W, Kuo Y-F, Sharma G. Pulmonary Rehabilitation Use in Older Adults with Chronic Obstructive Pulmonary Disease, 2003-2012. Journal of cardiopulmonary rehabilitation and prevention. 2016;36(5):375
[xi] Coventry PA, Hind D. Comprehensive pulmonary rehabilitation for anxiety and depression in adults with chronic obstructive pulmonary disease: systematic review and meta-analysis. Journal of psychosomatic research. 2007;63(5):551-565.
[xii] Lacasse Y, Goldstein R, Lasserson TJ, Martin S. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006;4(4)
[xiii] Lacasse Y, Goldstein R, Lasserson TJ, Martin S. Pulmonary rehabilitation for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2006;4(4).