TY - JOUR

T1 - New drug candidates for bipolar disorder

T2 - A nation-wide population-based study

AU - Kessing, Lars Vedel

AU - Rytgaard, Helene Charlotte

AU - Gerds, Thomas Alexander

AU - Berk, Michael

AU - Ekstrøm, Claus Thorn

AU - Andersen, Per Kragh

N1 - This article is protected by copyright. All rights reserved.

PY - 2019

Y1 - 2019

N2 - OBJECTIVE: Drug repurposing is an increasingly promising idea in many fields of medicine. We systematically used Danish nation-wide population-based registers to investigate whether continued use of non-aspirin NSAIDs, low dose aspirin, high dose aspirin, statins, allopurinol, and angiotensin agents decrease the rate of incident mania/bipolar disorder.METHODS: A nation-wide population-based longitudinal study using Poisson regression analyses including all persons in Denmark who purchased the exposure medication of interest and a random sample of 30% of the Danish population. The follow-up period comprised a 10 years period from 2005 to 2015. Two different outcome measures were included, 1) a diagnosis of mania/bipolar disorder at a psychiatric hospital contact as inpatient or outpatient and 2) a combined measure of a diagnosis of mania/bipolar disorder or initiation of lithium use.RESULTS: A total of 1,605,365 subjects were exposed to one of the six drugs of interest during the exposure period from 2005 to 2015, median age 57 years [quartiles: 43;69], female proportion: 53.1%. Continued use of low dose aspirin, statins, and angiotensin agents were associated with decreased rates of incident mania/bipolar disorder on both outcome measures. Continued uses of non-aspirin NSAIDs as well as high dose aspirin were associated with an increased rate of incident bipolar disorder. There were no statistically significant associations for allopurinol.CONCLUSIONS: The study supports the potential of agents acting on inflammation and the stress response system in bipolar disorder and illustrates that population-based registers can be used to systematically identify drugs with repurposing potentials. This article is protected by copyright. All rights reserved.

AB - OBJECTIVE: Drug repurposing is an increasingly promising idea in many fields of medicine. We systematically used Danish nation-wide population-based registers to investigate whether continued use of non-aspirin NSAIDs, low dose aspirin, high dose aspirin, statins, allopurinol, and angiotensin agents decrease the rate of incident mania/bipolar disorder.METHODS: A nation-wide population-based longitudinal study using Poisson regression analyses including all persons in Denmark who purchased the exposure medication of interest and a random sample of 30% of the Danish population. The follow-up period comprised a 10 years period from 2005 to 2015. Two different outcome measures were included, 1) a diagnosis of mania/bipolar disorder at a psychiatric hospital contact as inpatient or outpatient and 2) a combined measure of a diagnosis of mania/bipolar disorder or initiation of lithium use.RESULTS: A total of 1,605,365 subjects were exposed to one of the six drugs of interest during the exposure period from 2005 to 2015, median age 57 years [quartiles: 43;69], female proportion: 53.1%. Continued use of low dose aspirin, statins, and angiotensin agents were associated with decreased rates of incident mania/bipolar disorder on both outcome measures. Continued uses of non-aspirin NSAIDs as well as high dose aspirin were associated with an increased rate of incident bipolar disorder. There were no statistically significant associations for allopurinol.CONCLUSIONS: The study supports the potential of agents acting on inflammation and the stress response system in bipolar disorder and illustrates that population-based registers can be used to systematically identify drugs with repurposing potentials. This article is protected by copyright. All rights reserved.

U2 - 10.1111/bdi.12772

DO - 10.1111/bdi.12772

M3 - Journal article

C2 - 30873730

VL - 21

SP - 410

EP - 418

JO - Bipolar Disorders, Supplement

JF - Bipolar Disorders, Supplement

SN - 1399-2406

IS - 5

ER -