The Association between Use of ICS and Psychiatric Symptoms in Patients with COPD-A Nationwide Cohort Study of 49,500 Patients

Psychiatric side effects are well known from treatment with systemic corticosteroids. It is, however, unclear whether inhaled corticosteroids (ICS) have psychiatric side effects in patients with COPD. We conducted a nationwide cohort study in all Danish COPD outpatients who had respiratory medicine specialist-verified COPD, age >= 40 years, and no previous cancer. Prescription fillings of antidepressants and risk of admissions to psychiatric hospitals with either depression, anxiety or bipolar disorder were assessed by Cox proportional hazards models. We observed a dose-dependent increase in the risk of antidepressant-use with ICS cumulated dose (HR 1.05, 95% CI 1.03-1.07, p = 0.0472 with low ICS exposure, HR 1.10, 95% CI 1.08-1.12, p < 0.0001 with medium exposure, HR 1.15, 95% CI 1.11-1.15, p < 0.0001 with high exposure) as compared to no ICS exposure. We found a discrete increased risk of admission to psychiatric hospitals in the medium and high dose group (HR 1.00, 95% CI 0.98-1.03, p = 0.77 with low ICS exposure, HR 1.07, 95% CI 1.05-1.10, p < 0.0001 with medium exposure, HR 1.13, 95% CI 1.10-1.15, p < 0.0001 with high exposure). The association persisted when stratifying for prior antidepressant use. Thus, exposure to ICS was associated with a small to moderate increase in antidepressant-use and psychiatric admissions.