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 (OR 2.2[95%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 (IQR 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.

Long‐term morbidity and mortality in patients with Cushing's syndrome

“…Another Swedish study with 372 patients addressed the use of psychotropic drugs during long‐term remission. The need for antidepressants (odds ratio [OR] = 2.4) and sleeping pills (OR = 3.1) was still increased 5 years after remission compared to the healthy population, whereas the intake of drugs for hypertension (at time of diagnosis, OR = 11.2; in remission, OR = 1.3) and diabetes (at time of diagnosis, OR = 8.1; in remission, OR = 3.1) decreased 4 . These data underline the need for standardised long‐term management of these patients.…”

Impaired quality of life, but not cognition, is linked to a history of chronic hypercortisolism in patients with Cushing’s disease in remission

“…In conclusion, our study challenges the concept of irreversible memory impairment due to a specific and direct effect of hypercortisolism in patients below the age of 60. Although an increased vulnerability of the brain to cortisol excess in aged people cannot be excluded, our results suggest that various persisting co-morbidities of CD may be responsible for long-lasting impaired memory and should therefore be actively sought and adequately treated by expert specialists ( 46 ). The contrast between lasting impairment of QoL on the one hand and absence of major physical, psychological and cognitive sequelae on the other hand, may reflect irreversible consequences of cortisol excess.…”

“…However, both depression and long-term intake of antidepressant drugs can induce cognitive impairments ( 18 , 45 ). Similarly, the use of any psychotropic drug including sleeping pills, described in almost 1/3 of patients with a history of CD ( 46 ), was an exclusion criterion. No major psychological disturbance was found in our patients.…”

Increased Mortality Persists after Treatment of Cushing’s Disease: A Matched Nationwide Cohort Study

“…Another strength of the current study is that the diagnosis of CD was verified via the SPR since reliable identification of CD by using ICD coding has been questioned [ 2 ]. The SPR has a very high coverage [ 18 ] and has the advantage of including longitudinal data on remission status, treatments, tumor size, and hormone deficiencies. One previous study on mortality in patients with Cushing’s syndrome of both adrenal and pituitary origin used matched controls [ 17 ].…”

“…The SPR is a nationwide register that includes the vast majority of Swedish patients with CD [ 18 ]. The SPR contains information on the date of diagnosis, age, sex, treatment (surgery, radiotherapy, and pharmacological treatment), hormone deficiencies, tumor size [microadenomas (<10 mm), macroadenomas (≥10 mm), or invisible tumors], and biochemical remission status evaluations.…”