Adenosine Modulators and Calcium Channel Blockers in Bipolar Disorder Treatment

Young woman suffering from bipolar disorder, psychological diseases, schizophrenia. Happy young woman with and her ghostly sad twin behind. Concept of Bipolar disorder. Flat vector illustration.
Researchers investigated the effect of calcium channel blockers and adenosine modulators on patients with bipolar disorder.

A decreased risk for psychiatric hospitalization in bipolar disorder was associated with specific calcium channel blockers, diltiazem, and dihydropyridines. Results were inconclusive for this risk associated with the adenosine modulators, allopurinol and dipyridamole. These were among the study findings published in the Journal of Affective Disorders.

Treatment of bipolar disorder remains problematic with inadequate response, medication resistance, and significant costs. Drug repurposing vs traditional drug development is a faster, lower cost, less risky avenue to discover possible new pharmacotherapies. Researchers sought to determine the risk for psychiatric hospitalization among individuals with bipolar disorder associated with their exposure to specific calcium channel blockers (CCBs) and adenosine modulators.

They conducted a nationwide observational cohort study of individuals in Finland identified from the inpatient, specialized outpatient, sickness absence, and disability pension registers (1996-2018) with bipolar disorder (BD) (N=60,045; 56% women; median 40 years of age [IQR 28-52 years]). The primary outcome was psychiatric hospitalization.

Researchers found that use of CCBs (N=9056) when analyzed together associated with a lowered risk for hospitalization due to affective symptoms (adjusted hazard ratio [aHR] 0.83; 95% CI, 0.78–0.88). Analyzed individual CCBs revealed verapamil was not associated with reduced risk (aHR 0.93; 95% CI, 0.73-1.19). However, diltiazem (aHR 0.71; 95% CI, 0.55-0.91) and dihydropyridines (aHR 0.83; 95% CI, 0.78-0.89) were associated with decreased hospitalization risk.

Researchers also found that use of adenosine modulators (N=2967) analyzed together associated with a lowered risk for hospitalization due to affective symptoms (aHR 0.87; 95% CI, 0.79-0.96). Individual analysis revealed marginal decreases with allopurinal (aHR 0.85; 95% CI, 0.74-0.97) and dipyridamole (aHR 0.89; 95% CI, 0.78-1.00). The negative control, thiazide diuretic (N=1286), showed no association with risk for hospitalization due to affective symptoms.

Study limitations include the observational design leading to selection bias, problematic result comparisons with previous randomized controlled trials due to unavailability of data in the current study, and lack of adjustment for psychosocial treatments.

Researchers concluded that, “Dihydropyridines and diltiazem were associated with a decreased risk of psychiatric hospitalization in bipolar disorder.” They found inconclusive results for allopurinol and dipyridamole related to the risk for psychiatric hospitalization.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Lintunen J, Lähteenvuo M, Tanskanen A, Tiihonen J, Taipale H. Allopurinol, dipyridamole and calcium channel blockers in the treatment of bipolar disorder – a nationwide cohort study. J Affect Disord. 2022;313:43-48. doi:10.1016/j.jad.2022.06.040