Adenosine modulators and calcium channel blockers as add-on treatment for schizophrenia

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 r...

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Autores principales:	Jonne Lintunen, Markku Lähteenvuo, Jari Tiihonen, Antti Tanskanen, Heidi Taipale
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Psychiatry RC435-571
Acceso en línea:	https://doaj.org/article/39076ad68fa7412396994fa04284c3ea
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spelling	oai:doaj.org-article:39076ad68fa7412396994fa04284c3ea2021-12-02T13:48:40ZAdenosine modulators and calcium channel blockers as add-on treatment for schizophrenia10.1038/s41537-020-00135-y2334-265Xhttps://doaj.org/article/39076ad68fa7412396994fa04284c3ea2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41537-020-00135-yhttps://doaj.org/toc/2334-265XAbstract 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.Jonne LintunenMarkku LähteenvuoJari TiihonenAntti TanskanenHeidi TaipaleNature PortfolioarticlePsychiatryRC435-571ENnpj Schizophrenia, Vol 7, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Psychiatry RC435-571
spellingShingle	Psychiatry RC435-571 Jonne Lintunen Markku Lähteenvuo Jari Tiihonen Antti Tanskanen Heidi Taipale Adenosine modulators and calcium channel blockers as add-on treatment for schizophrenia
description	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.
format	article
author	Jonne Lintunen Markku Lähteenvuo Jari Tiihonen Antti Tanskanen Heidi Taipale
author_facet	Jonne Lintunen Markku Lähteenvuo Jari Tiihonen Antti Tanskanen Heidi Taipale
author_sort	Jonne Lintunen
title	Adenosine modulators and calcium channel blockers as add-on treatment for schizophrenia
title_short	Adenosine modulators and calcium channel blockers as add-on treatment for schizophrenia
title_full	Adenosine modulators and calcium channel blockers as add-on treatment for schizophrenia
title_fullStr	Adenosine modulators and calcium channel blockers as add-on treatment for schizophrenia
title_full_unstemmed	Adenosine modulators and calcium channel blockers as add-on treatment for schizophrenia
title_sort	adenosine modulators and calcium channel blockers as add-on treatment for schizophrenia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/39076ad68fa7412396994fa04284c3ea
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Adenosine modulators and calcium channel blockers as add-on treatment for schizophrenia

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