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Published on: November 11, 2016
A systematic review of calcium channel antagonists in bipolar disorder and some considerations for their future
A Cipriani1,2, K Saunders1,2, M-J Attenburrow1,2
1Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
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.
Insights
L-type calcium channel (LTCC) antagonists show no efficacy for acute mania treatment. Despite genetic links to bipolar disorder, current evidence does not support their use, necessitating further research into targeted therapies.
Area of Science:
- Neuroscience
- Pharmacology
- Psychiatry
Background:
- L-type calcium channel (LTCC) antagonists have a long history in bipolar disorder treatment, yet remain unestablished therapies.
- Recent discoveries link LTCC genes to the genetic basis of bipolar disorder and related phenotypes, renewing interest in these drugs.
Purpose of the Study:
- To systematically review the efficacy of LTCC antagonists in treating and preventing bipolar disorder.
- To evaluate the current evidence and discuss future directions for LTCC antagonist development in bipolar disorder.
Main Methods:
- Conducted a systematic review of 23 eligible studies.
- Focused on six randomized, double-blind, controlled clinical trials investigating verapamil in acute mania.
Main Results:
- No evidence was found for the effectiveness of verapamil in treating acute mania.
- Data on other LTCC antagonists and illness phases are limited to observational studies, precluding robust conclusions.
Conclusions:
- Despite genetic evidence for calcium signaling dysfunction in bipolar disorder, LTCC antagonists lack proven efficacy.
- Future development should focus on brain-selective LTCC ligands and personalized approaches using genetic and molecular data for improved bipolar disorder pharmacotherapy.
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