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PMID: 27240535 Published · ppublish English Journal Article Review Systematic Review

A systematic review of calcium channel antagonists in bipolar disorder and some considerations for their future development.

Molecular psychiatry ·Vol. 21 ·No. 10 ·2016-00-00 ·Pages 1324-32

Cipriani A, Saunders K, Attenburrow MJ, Stefaniak J, Panchal P, Stockton S, Lane TA, Tunbridge EM, Geddes JR, Harrison PJ

Abstract

l-type calcium channel (LTCC) antagonists have been used in bipolar disorder for over 30 years, without becoming an established therapeutic approach. Interest in this class of drugs has been rekindled by the discovery that LTCC genes are part of the genetic aetiology of bipolar disorder and related phenotypes. We have therefore conducted a systematic review of LTCC antagonists in the treatment and prophylaxis of bipolar disorder. We identified 23 eligible studies, with six randomised, double-blind, controlled clinical trials, all of which investigated verapamil in acute mania, and finding no evidence that it is effective. Data for other LTCC antagonists (diltiazem, nimodipine, nifedipine, methyoxyverapamil and isradipine) and for other phases of the illness are limited to observational studies, and therefore no robust conclusions can be drawn. Given the increasingly strong evidence for calcium signalling dysfunction in bipolar disorder, the therapeutic candidacy of this class of drugs has become stronger, and hence we also discuss issues relevant to their future development and evaluation. In particular, we consider how genetic, molecular and pharmacological data can be used to improve the selectivity, efficacy and tolerability of LTCC antagonists. We suggest that a renewed focus on LTCCs as targets, and the development of 'brain-selective' LTCC ligands, could be one fruitful approach to innovative pharmacotherapy for bipolar disorder and related phenotypes.

MeSH Terms
Bipolar Disorder/drug therapy Calcium Channel Blockers/metabolism,therapeutic use Calcium Channels, L-Type/genetics Double-Blind Method Humans Isradipine/therapeutic use Nimodipine/therapeutic use Verapamil/therapeutic use
Chemicals
Calcium Channel Blockers Calcium Channels, L-Type Nimodipine Verapamil Isradipine
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Cipriani A ORCID
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK. | Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
Saunders K
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK. | Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
Attenburrow M-J
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK. | Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
Stefaniak J
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
Panchal P
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK. | Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
Stockton S
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK. | Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
Lane T A
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
Tunbridge E M
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK. | Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
Geddes J R
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK. | Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
Harrison P J
Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK. | Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK.
Conflict of Interest

In the past 2 years: AC has served as an expert witness for a patent litigation case about quetiapine extended-release. PJH has served as an expert witness on patent litigation involving drugs used to treat bipolar disorder. The remaining authors declare no conflicts of interest.

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Article Info
Journal
Molecular psychiatry
Abbr.
Mol Psychiatry
ISSN
1476-5578
DOI
10.1038/mp.2016.86
Published
2016-00-00
Epub
2016-00-31
Pages
1324-32
Language
English
Region
England
NLM ID
9607835
PMCID
PMC5030455
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1038/mp.2016.86 PMC Full Text View journal details
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