Abstract
Relapses remain common among individuals with schizophrenia indicating a need for improved treatments. Creating a completely new drug molecule is expensive and time consuming, and therefore drug repurposing should be considered. Aim of this study was to investigate the risk of psychiatric rehospitalization associated with use of adenosine modulators (AMs) and calcium channel blockers (CCBs) in schizophrenia. Individuals diagnosed with schizophrenia (N = 61,889) in inpatient care between 1972–2014 in Finland were included. The follow-up lasted from 1996 to 2017. Main exposures were use of AMs (allopurinol and dipyridamole) and CCBs (dihydropyridines, diltiazem, and verapamil). Thiazide diuretics were used as a negative control. Within-individual models in stratified Cox regression were used and adjusted hazard ratios (HR) with 95% confidence intervals (CIs) are reported. Use of AMs was associated with a reduced risk of psychiatric rehospitalization on drug class level (HR 0.74, 95% CI 0.65–0.84, P < 0.0001), as well as on the level of individual drugs (allopurinol HR 0.82, 95% CI 0.70–0.97, P = 0.02; dipyridamole HR 0.65, 95% CI 0.55–0.77, P < 0.0001). Use of CCBs was associated with a reduced risk of psychiatric rehospitalization on drug class level (HR 0.81, 95% CI 0.77–0.86, P < 0.0001). From the different CCBs, only exposure to dihydropyridines was associated with a reduced risk (HR 0.79, 95% CI 0.74–0.84, P < 0.0001). No effect was observed for the negative control, thiazide diuretics (HR 0.96, 0.90–1.02, P = 0.20). The effects of dipyridamole and dihydropyridines were more pronounced among younger persons and combination of AMs, and CCBs was associated with a lower risk than either drug class as monotherapy. These results indicate a need for randomized controlled trials of these drugs.
Highlights
Antipsychotics are the basis of schizophrenia treatment[1]
Our results suggest that use of adenosine modulators (AMs) and calcium channel blockers (CCBs) as add-on treatment for schizophrenia could be beneficial in decreasing the risk of psychiatric hospitalizations
On the level of individual drugs, the most beneficial results were noted for dipyridamole, and of CCBs, only dihydropyridines were associated with a lower risk
Summary
Antipsychotics are the basis of schizophrenia treatment[1]. Despite their use, many patients continue to have symptoms, and the rate of psychiatric rehospitalization among persons with schizophrenia is high[2]. Creating a completely new drug molecule is expensive and time consuming, and to overcome these drawbacks drug repurposing should be considered. Novel targets for drugs that have been used for other indications and proven to be safe can be found[3]. Adenosine modulators (AMs), such as allopurinol and dipyridamole, and calcium channel blockers (CCBs) have been considered[4]
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