New drug candidates for depression – a nationwide population‐based study

• Published in: Acta psychiatrica Scandinavica Vol. 139; no. 1; pp. 68 - 77
• Main Authors: Kessing, L.V., Rytgaard, H. C., Gerds, T. A., Berk, M., Ekstrøm, C. T., Andersen, P. K.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.01.2019
• Subjects: Adult; Aged; Allopurinol; Allopurinol - adverse effects; Allopurinol - therapeutic use; Angiotensin; Angiotensins - adverse effects; Angiotensins - therapeutic use; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Antidepressants; Antidepressive Agents - therapeutic use; Aspirin; Aspirin - adverse effects; Aspirin - therapeutic use; Denmark - epidemiology; Depression - diagnosis; Depression - drug therapy; Depression - epidemiology; depressive disorder; Depressive Disorder - diagnosis; Depressive Disorder - drug therapy; Depressive Disorder - epidemiology; Diagnosis; Drug development; Drug dosages; Drug Repositioning - methods; Drug Repositioning - statistics & numerical data; drug repurposing; Female; Gout Suppressants - adverse effects; Gout Suppressants - therapeutic use; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Incidence; inflammation; Inflammation - drug therapy; Male; Mental depression; Middle Aged; Nonsteroidal anti-inflammatory drugs; NSAID; Outcome Assessment, Health Care; Population; Population studies; Population-based studies; Registries; Statins; stress; Stress, Physiological - drug effects; Denmark; stress; drug repurposing; inflammation; NSAID; statins; angiotensin; depressive disorder; aspirin; antidepressants; allopurinol
• ISSN: 0001-690X; 1600-0447; 1600-0447
• DOI: 10.1111/acps.12957

Objective To investigate whether continued use of non‐aspirin NSAID, low‐dose aspirin, high‐dose aspirin, statins, allopurinol and angiotensin agents decreases the rate of incident depression using Danish nationwide population‐based registers. Methods All persons in Denmark who purchased the exposure medications of interest between 1995 and 2015 and a random sample of 30% of the Danish population was included in the study. Two different outcome measures were included, (i) a diagnosis of depressive disorder at a psychiatric hospital as in‐patient or out‐patient and (ii) a combined measure of a diagnosis of depression or use of antidepressants. Results A total of 1 576 253 subjects were exposed to one of the six drugs of interest during the exposure period from 2005 to 2015. Continued use of low‐dose aspirin, statins, allopurinol and angiotensin agents was associated with a decreased rate of incident depression according to both outcome measures. Continued uses of non‐aspirin NSAIDs as well as high‐dose aspirin were associated with an increased rate of incident depression. Conclusion The findings support the potential of agents acting on inflammation and the stress response system in depression as well as the potential of population‐based registers to systematically identify drugs with repurposing potential.