Allopurinol, dipyridamole and calcium channel blockers in the treatment of bipolar disorder - A nationwide cohort study

Jonne Lintunen; Markku Lähteenvuo; Antti Tanskanen; Jari Tiihonen; Heidi Taipale

doi:10.1016/j.jad.2022.06.040

Allopurinol, dipyridamole and calcium channel blockers in the treatment of bipolar disorder - A nationwide cohort study

J Affect Disord. 2022 Sep 15:313:43-48. doi: 10.1016/j.jad.2022.06.040. Epub 2022 Jun 23.

Authors

Jonne Lintunen¹, Markku Lähteenvuo², Antti Tanskanen³, Jari Tiihonen⁴, Heidi Taipale⁵

Affiliations

¹ Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland. Electronic address: jonnel@student.uef.fi.
² Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland.
³ Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Psychiatry Research, Stockholm City Council, Stockholm, Sweden.
⁴ Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Psychiatry Research, Stockholm City Council, Stockholm, Sweden; Neuroscience Center, University of Helsinki, Helsinki, Finland.
⁵ Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Center for Psychiatry Research, Stockholm City Council, Stockholm, Sweden; School of Pharmacy, University of Eastern Finland, Kuopio, Finland.

PMID: 35753501
DOI: 10.1016/j.jad.2022.06.040

Abstract

Background: Improved treatments for bipolar disorder (BD) are needed. Drug repurposing aims to find novel targets for drugs that have been used for other indications. This study investigated the risk of psychiatric hospitalization associated with use of calcium-channel blockers (CCBs; dihydropyridines, diltiazem, verapamil) and adenosine modulators (allopurinol, dipyridamole) in BD in within-individual design.

Methods: Individuals diagnosed with BD (ICD-10: F30-F31) were identified from the inpatient, specialized outpatient, sickness absence, and disability pension registers during 1996-2018 in Finland (N = 60,045). The main outcome was hospitalization due to affective symptoms (ICD-10: F30-F39). Within-individual models in stratified Cox regression were used and adjusted hazard ratios (aHR) with 95 % confidence intervals (CIs) reported.

Results: Use of CCBs was associated with a decreased risk of hospitalization due to affective symptoms (aHR 0.83, 95 % CI 0.78-0.88) when all CCBs were analyzed together. Of specific CCBs, use of diltiazem (0.71, 0.55-0.91) and dihydropyridines (0.83, 0.78-0.89) were associated with a decreased risk but verapamil was not (0.93, 0.73-1.19). Use of adenosine modulators in general was associated with a decreased risk of hospitalizations due to affective symptoms (0.87, 0.79-0.96). Both allopurinol (0.85, 0.74-0.97) and dipyridamole (0.89, 0.78-1.00) were associated with a marginally decreased risk. Thiazide diuretic use as a negative control was not associated with the risk of hospitalization due to affective symptoms (0.97, 0.83-1.13).

Limitations: Due to the observational nature of this study, causation cannot be confirmed.

Conclusions: Dihydropyridines and diltiazem were associated with a decreased risk of psychiatric hospitalization in bipolar disorder. Results for allopurinol and dipyridamole were inconclusive.

Keywords: Adenosine; Allopurinol; Bipolar disorder; Calcium channel blockers; Dipyridamole; Drug repurposing.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adenosine / therapeutic use
Allopurinol / adverse effects
Bipolar Disorder* / drug therapy
Calcium Channel Blockers / adverse effects
Cohort Studies
Dihydropyridines* / therapeutic use
Diltiazem / therapeutic use
Dipyridamole / adverse effects
Humans

Substances

Calcium Channel Blockers
Dihydropyridines
Allopurinol
Dipyridamole
Diltiazem
Adenosine