Exploring Duloxetine for Depression in COPD: A Pilot Study

Abebaw Yohannes, MSc, PhD
Credit: American Lung Association

Prevalence of depression: Chronic obstructive pulmonary disease (COPD) is a major cause of disability, morbidity, and premature mortality.^1,2 Approximately, two-thirds of COPD patients live with 2 or more comorbidities.^4,5 Of these, over 40% suffer from co-morbid depression that warrants medical intervention; however, many remain undiagnosed and thus untreated.⁶ Untreated depression is associated with poor compliance to medical treatment, early dropout from pulmonary rehabilitation (PR) and increased risk of exacerbation,emergency care utilization, and hospital readmission.^8,9,10,11,12

Why this study needed?

To date, pharmacological interventions that have been employed to treat comorbid depression in patients with moderate-to-severe COPD have led to inconclusive results.^13,14 Selective serotonin reuptake inhibitors (SSRI) and selective norepinephrine reuptake inhibitors (SNRI) are the first line of treatment for major depression in the general population because of their efficacy and their safety profile compared to tricyclic antidepressants (TCA).¹⁵ In contrast, SSRI/SNRI have been associated with elevated risk of poor outcomes in patients with COPD in large observational data-based studies.^16,17 However, all case-control epidemiological designs, even self-controlled studies, and even after adjusting for possible confounders, suffer from residual confounding. That is, people who require antidepressants are likely to be very different from those who do not. Given the negative impact of depression in patients with COPD, a proper randomized controlled trial is needed. The role of these agents has not been systematically examined in randomized controlled trial in patients with COPD.

Purpose of the study: The overall goal of this pilot study is to examine the feasibility of using duloxetine (an SNRI)in patients with moderate to severe COPD who suffer from comorbid depression. We will test the hypothesis that the use of duloxetine is feasible and acceptable in the treatment of depression (primary outcome) and improves anxiety, quality of life (QoL), dyspnea, and exercise capacity (secondary outcomes). To test this hypothesis, we propose three phases for this 2-center study to: (1) determine acceptability and identify potential barriers to antidepressant treatment from COPD patients, (2) identify barriers and experiences of treating depression in COPD by primary care and pulmonary physicians and (3) generate pilot data from an open-label study using duloxetine to ascertain acceptability, compliance, tolerability in patients with COPD with comorbid depression. Our goal is to generate the preliminary data necessary for a subsequent interventional multi-center trial of antidepressant treatment in patients with COPD and comorbid depression.

Specific Aims:

Aim 1: To examine the attitudes, perceptions, and beliefs of patients with moderate-to-severe patients with COPD (N= 30) living with depression using a semi-structured qualitative interview. Patients will ber ecruited from the outpatient clinics of University Alabama Healthcare System and (UAB) Baylor Collegeof Medicine (BCM). We will first elucidate the acceptability and attitudes of patients about antidepressant drug therapy and probe any fears and misconceptions as well barriers and facilitators about this treatment.COPD patients with a Hospital Anxiety Depression Scale (HADS), HADS-depression score > 8 will be recruited for this phase of the study [18].

Aim 2: To examine attitudes, experiences, and perceptions of healthcare providers (pulmonary physicians and primary care physicians) about treatment of comorbid depression in patients with COPD. We plan to recruit healthcare providers (n = 30) for the survey using the local physician networks at UAB and BCM. We plan to develop two educational booklets from Aim 1 to support patients when receiving antidepressant therapy and from Aim 2 to create provider materials to support physicians Aim 3.

Aim 3: To conduct an open-label pilot study of Duloxetine therapy in patients with COPD and comorbid depression to 1) establish its tolerability and feasibility (e.g., recruitment rates, adherence to intervention, completion, and attrition rates), (primary outcomes) and 2) examine its preliminary effects on depression, anxiety, QoL, dyspnea, exercise capacity, and loneliness (secondary outcomes). We will recruit (N = 15) COPD patients with depressive symptoms based on a HADS depression score > 8 and depression diagnosis confirmed by the Mini International Neuropsychiatric Interview diagnostic interview.

We plan to treat them with duloxetine treatment for 12 weeks. Duloxetine therapy starts at 30mg and titrated to 60mg after 2 weeks and further titrated to 90mg after 4 weeks and maximally titrated (as tolerated) to 120 mg after 6 weeks. In each visit, adverse events will be monitored using a pre-specified protocol. Findings of the pilot trial will help us to inform the approach to take for a subsequent larger randomized controlled trial to determine the sample size and the power of the study.