Psychotropic Drugs in Patients with Cushing's Disease Before Diagnosis and at Long-Term Follow-Up: A Nationwide Study

Abstract

Context: Psychiatric symptoms are common in Cushing's disease (CD) and seem only partly reversible following treatment.

Objective: To investigate drug dispenses associated to psychiatric morbidity in CD patients before treatment and during long-term follow-up.

Design: Nationwide longitudinal register-based study.

Setting: University Hospitals in Sweden.

Subjects: CD patients diagnosed between 1990 and 2018 (N = 372) were identified in the Swedish Pituitary Register. Longitudinal data was collected from 5 years before, at diagnosis, and during follow-up. Four matched controls per patient were included. Cross-sectional subgroup analysis of 76 patients in sustained remission was also performed.

Main outcome measures: Data from the Swedish Prescribed Drug Register and the Patient Register.

Results: In the 5-year period before and at diagnosis, use of antidepressants (odds ratio [OR] 2.2 [95% confidence interval (CI) 1.3-3.7]) and 2.3 [1.6-3.5]), anxiolytics [2.9 (1.6-5.3) and 3.9 (2.3-6.6)], and sleeping pills [2.1 (1.2-3.7) and 3.8 (2.4-5.9)] was more common in CD than controls. ORs remained elevated at 5-year follow-up for antidepressants [2.4 (1.5-3.9)] and sleeping pills [3.1 (1.9-5.3)]. Proportions of CD patients using antidepressants (26%) and sleeping pills (22%) were unchanged at diagnosis and 5-year follow-up, whereas drugs for hypertension and diabetes decreased. Patients in sustained remission for median 9.3 years (interquartile range 8.1-10.4) had higher use of antidepressants [OR 2.0 (1.1-3.8)] and sleeping pills [2.4 (1.3-4.7)], but not of drugs for hypertension.

Conclusions: Increased use of psychotropic drugs in CD was observed before diagnosis and remained elevated regardless of remission status, suggesting persisting negative effects on mental health. The study highlights the importance of early diagnosis of CD, and the need for long-term monitoring of mental health.

Keywords: Cushing’s syndrome; depression; hypercortisolism; neuropsychiatry; sleeping disorder.

Figure 1.

Outline of the study and eligible patients for each analysis. Age is median (IQR) at diagnosis.

Figure 2.

Cumulative proportion of subjects (CD n = 103, controls n = 412) with first drug dispense from start of observation (5 years before) to date of diagnosis. x-axis: years before diagnosis; y-axis: proportion of patients. P-values refer to log rank (Mantel-Cox).

Figure 3.

Proportions of CD patients with drug dispenses at diagnosis and 5- and 10-year follow-up. Difference of proportions were tested with Fisher exact 2-sided test at 2 levels: diagnosis vs 5-year and diagnosis vs 10-year, respectively. Only significant changes are indicated: *P-value < 0.05; **P-value < 0.01; ***P-value < 0.001.