Highlight
1. Individuals with autoimmune Addison’s disease (AAD) show higher use of hypnotics/sedatives, anxiolytics, and antidepressants before diagnosis compared to matched controls.
2. The use of hypnotics/sedatives remains significantly elevated after diagnosis, suggesting persistent sleep disturbances.
3. Early mental health symptoms associated with AAD may be misdiagnosed, underscoring the importance of awareness for clinicians.
4. Insomnia emerges as a common and enduring symptom in patients with AAD.
Study Background and Disease Burden
Autoimmune Addison’s disease (AAD) is a rare endocrine disorder characterized by destruction of the adrenal cortex, leading to deficiencies in cortisol and aldosterone. While physical manifestations such as fatigue, weight loss, and hypotension are well recognized, the impact of AAD on mental health remains less well characterized. Psychological symptoms, including mood disturbances and insomnia, could precede diagnosis but often remain under-recognized by clinicians. Given that early clinical features may mimic psychiatric disorders, there is a risk of misdiagnosis that delays appropriate treatment. Understanding the patterns of psychotropic drug use around AAD diagnosis could provide valuable insight into early disease manifestations and assist in earlier detection. This also addresses an unmet medical need by highlighting the intersection of endocrinology and psychiatry in AAD management.
Study Design
This population-based cohort study utilized comprehensive national health and population registers in Sweden, coupled with the Swedish Addison Registry, to identify individuals diagnosed with AAD between July 2006 and December 2019. A total of 963 AAD patients were matched with 9,366 population controls. The Swedish Prescribed Drug Register provided annual dispensation data on psychotropic medications, including antipsychotics (ATC N05A), anxiolytics (N05B), hypnotics/sedatives (N05C), and antidepressants (N06A) from three years before up to three years after AAD diagnosis. Additionally, a cross-sectional analysis of psychotropic drug use in the year 2019 was performed to assess longer-term patterns.
Key Findings
The study found significantly increased use of hypnotics/sedatives, anxiolytics, and antidepressants within the year preceding AAD diagnosis compared to matched controls. The odds ratios (ORs) were 1.72 (95% CI 1.40-2.11) for hypnotics/sedatives, 1.38 (1.07-1.78) for anxiolytics, and 1.29 (1.05-1.59) for antidepressants, indicating a robust association during this critical period.
Post-diagnosis, the elevated use of hypnotics/sedatives persisted consistently, with ORs ranging from 1.42 to 1.78 across the three years following AAD diagnosis. No significant differences were noted in antipsychotic dispensation after diagnosis, suggesting that psychotic disorders are not differentially prevalent in this population. The cross-sectional analysis for the year 2019 confirmed ongoing elevated hypnotic/sedative use (OR 1.31, 1.01-1.70), reinforcing the persistence of sleep-related issues.
These findings strongly suggest that early neuropsychiatric symptoms, particularly those related to anxiety, depression, and insomnia, may either be prodromal signs of AAD or misdiagnosed as primary psychiatric disorders. Insomnia appears especially prominent and enduring among affected individuals.
Expert Commentary
The study by Öster et al. provides valuable clinical insights by linking psychotropic drug dispensation data with AAD diagnosis timelines. It underscores the need for heightened clinical suspicion for AAD in patients presenting with unexplained neuropsychiatric symptoms, particularly when accompanied by systemic signs of adrenal insufficiency.
From a mechanistic perspective, cortisol deficiency in AAD can disrupt circadian rhythms, affect neurotransmitter systems, and impair stress response, contributing to mood disorders and sleep disturbances. This biological plausibility supports the observed patterns of psychotropic use.
However, limitations include the observational design and lack of direct clinical psychiatric assessments, which preclude definitive causal conclusions. The Swedish health registers provide high validity and large sample size, enhancing generalizability to European populations but extrapolations to other ethnicities should be made cautiously.
Conclusion
This study highlights that psychotropic drug use, especially hypnotics and sedatives, may serve as a signal for the early presence of autoimmune Addison’s disease before formal diagnosis. Early recognition of mental health symptoms linked to AAD could lead to timely endocrine evaluation and appropriate treatment initiation, potentially improving patient outcomes. Additionally, the persistence of insomnia after diagnosis calls for integrated management strategies addressing both endocrine and psychiatric needs in AAD patients. Further research should aim at elucidating the neuroendocrine mechanisms underlying these psychiatric symptoms and assessing interventions to mitigate their impact.
References
Öster S, Spelman T, Bensing S, Skov J. Psychotropic drug use in patients with autoimmune Addison’s disease: a Swedish population-based cohort study. Eur J Endocrinol. 2025 Jul 31;193(2):262-269. doi: 10.1093/ejendo/lvaf155. PMID: 40751493.
