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

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          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.

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          Most cited references37

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          External review and validation of the Swedish national inpatient register

          Background The Swedish National Inpatient Register (IPR), also called the Hospital Discharge Register, is a principal source of data for numerous research projects. The IPR is part of the National Patient Register. The Swedish IPR was launched in 1964 (psychiatric diagnoses from 1973) but complete coverage did not begin until 1987. Currently, more than 99% of all somatic (including surgery) and psychiatric hospital discharges are registered in the IPR. A previous validation of the IPR by the National Board of Health and Welfare showed that 85-95% of all diagnoses in the IPR are valid. The current paper describes the history, structure, coverage and quality of the Swedish IPR. Methods and results In January 2010, we searched the medical databases, Medline and HighWire, using the search algorithm "validat* (inpatient or hospital discharge) Sweden". We also contacted 218 members of the Swedish Society of Epidemiology and an additional 201 medical researchers to identify papers that had validated the IPR. In total, 132 papers were reviewed. The positive predictive value (PPV) was found to differ between diagnoses in the IPR, but is generally 85-95%. Conclusions In conclusion, the validity of the Swedish IPR is high for many but not all diagnoses. The long follow-up makes the register particularly suitable for large-scale population-based research, but for certain research areas the use of other health registers, such as the Swedish Cancer Register, may be more suitable.
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            Stress and the brain: from adaptation to disease.

            In response to stress, the brain activates several neuropeptide-secreting systems. This eventually leads to the release of adrenal corticosteroid hormones, which subsequently feed back on the brain and bind to two types of nuclear receptor that act as transcriptional regulators. By targeting many genes, corticosteroids function in a binary fashion, and serve as a master switch in the control of neuronal and network responses that underlie behavioural adaptation. In genetically predisposed individuals, an imbalance in this binary control mechanism can introduce a bias towards stress-related brain disease after adverse experiences. New candidate susceptibility genes that serve as markers for the prediction of vulnerable phenotypes are now being identified.
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              The new Swedish Prescribed Drug Register--opportunities for pharmacoepidemiological research and experience from the first six months.

              To describe the content and potentials of the new Swedish national register on prescribed and dispensed medicines. The Swedish Prescribed Drug Register contains information about age, sex and unique identifier of the patient as well as the prescriber's profession and practice. Information regarding drug utilization and expenditures for prescribed drugs in the entire Swedish population was extracted from the first six months July-December 2005 and compared with total drug sales in the country including OTC and hospital use. The total quantity of drugs sold in Sweden was 2666 million DDDs, corresponding to 1608 DDD/1000 inhabitants daily. The total expenditures were 1.6 billion Euro. The prescribed drugs, included in the register, accounted for 84% of the total utilization and 77% of the total expenditures. About half of all men and two-thirds of all women in the country purchased drugs. The proportion increased by age. The most common drugs for chronic treatment were diuretics among women (8.8% of the population) and antithrombotic agents among men (7.6%). Psychotropic drugs, corticosteroids and analgesics were more common among women, while men used antithrombotic agents, antidiabetic drugs, lipid lowering agents and ACE inhibitors to a greater extent. The new register provides valuable data on exposure to drugs and is useful to study patterns of drug utilization. The possibilities for record linkage to other health registers gives from an international perspective good opportunities to explore drug and disease associations and the risks, benefits, effectiveness and health economical effects of drug use.
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                Author and article information

                Journal
                J Clin Endocrinol Metab
                J Clin Endocrinol Metab
                jcem
                The Journal of Clinical Endocrinology and Metabolism
                Oxford University Press (US )
                0021-972X
                1945-7197
                June 2021
                10 February 2021
                10 February 2021
                : 106
                : 6
                : 1750-1760
                Affiliations
                [1 ] Department of Internal Medicine, Kalmar, Region of Kalmar County , Kalmar, Sweden
                [2 ] Department of Biomedical and Clinical Sciences, Linköping University , Linköping, Sweden
                [3 ] Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg , Gothenburg, Sweden
                [4 ] Department of Endocrinology, Sahlgrenska University Hospital , Gothenburg, Sweden
                [5 ] Department of Endocrinology, Karolinska University Hospital , Stockholm, Sweden
                [6 ] Department of Molecular Medicine and Surgery, Karolinska Institutet , Stockholm, Sweden
                [7 ] Department of Public Health and Clinical Medicine, Umeå University , Umeå, Sweden
                [8 ] Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University , Uppsala, Sweden
                [9 ] Department of Endocrinology and Diabetes, Uppsala University Hospital , Uppsala, Sweden
                [10 ] Department of Endocrinology in Linköping and Department of Health, Medicine and Caring Sciences, Linköping University , Linköping, Sweden
                [11 ] Department of Endocrinology, Skåne University Hospital, University of Lund , Malmö, Sweden
                [12 ] Faculty of Medical Sciences, Örebro University , Örebro, Sweden
                Author notes
                Correspondence: Daniel Bengtsson, MD, Department of Internal Medicine, Hälsogränd 2, 391 85 Kalmar, Sweden. Email: daniel.bengtsson@ 123456liu.se .
                Author information
                https://orcid.org/0000-0003-4408-6435
                https://orcid.org/0000-0003-0204-9492
                https://orcid.org/0000-0003-2488-0375
                https://orcid.org/0000-0002-6471-9503
                https://orcid.org/0000-0003-4514-5193
                https://orcid.org/0000-0001-8732-7361
                https://orcid.org/0000-0002-3980-1927
                https://orcid.org/0000-0002-4844-8336
                https://orcid.org/0000-0001-9456-2044
                Article
                dgab079
                10.1210/clinem/dgab079
                8118365
                33567076
                8ab7b0e9-3564-4d75-a501-6e8980027183
                © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 13 December 2020
                : 03 February 2021
                : 12 March 2021
                Page count
                Pages: 11
                Categories
                Clinical Research Articles
                AcademicSubjects/MED00250

                Endocrinology & Diabetes
                cushing’s syndrome,hypercortisolism,neuropsychiatry,depression,sleeping disorder

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