Calcium antagonists for Duchenne muscular dystrophy.
BACKGROUND
Duchenne muscular dystrophy (DMD) is a progressive muscle condition starting in childhood, leading to severe disability and a shortened life span. It is due to severe deficiency of the protein dystrophin which performs both structural and signalling roles within skeletal and cardiac myocytes. Calcium accumulates in dystrophic muscle cells and plays a role in cell damage. It has been hypothesised that use of calcium antagonists might reduce this calcium load and its toxic effect on muscle cells.


OBJECTIVE
To evaluate the effects of calcium antagonists on muscle function and muscle strength in people with DMD.


METHODS
The Cochrane Neuromuscular Disease Group Trials Register (February 2008), MEDLINE (from January 1950 to March 2008) and EMBASE (from January 1947 to March 2008) were searched. Search terms were 'calcium antagonists' or 'calcium channel blocker' or 'dantrolene' or 'verapamil' or 'nifedipine' or 'flunarizine' or 'diltiazem' or 'amlodipine' or 'nicardipine' and 'Muscular Dystrophy, Duchenne'. Bibliographies in reports of any trials were also searched.


METHODS
All randomised or quasi-randomised controlled trials of any calcium antagonist in people with DMD.


METHODS
Both authors assessed all identified trials for inclusion in the study on the basis of whether they fulfilled the selection criteria. Both authors extracted data from the trials and assessed the methodological quality. Had there been more than one trial of the same intervention and outcome of sufficient methodological quality, we had planned to undertake a meta-analysis.


RESULTS
Five randomised or quasi-randomised double-blind trials fulfilled the selection criteria, but were not sufficiently comparable to undertake a meta-analysis. The drugs studied were verapamil (8 participants), diltiazem (56 participants), nifedipine (105 participants) and flunarizine (27 participants). There were limitations in the description of blinding and randomisation, and definition of outcome measures. One trial, using verapamil, showed a difference between groups in muscle force measured by ergometry, but also revealed cardiac side effects. The numbers of people included in the trials were low, and so the studies may not have included enough people for sufficient power to detect small differences in muscle force or function between placebo and control groups. In addition, calcium antagonists were in an early stage of development and some of the second generation drugs that have a better side effect profile, such as amlodipine, have not been studied.


CONCLUSIONS
There is no evidence to show a significant beneficial effect of calcium antagonists on muscle function in DMD.
Division of Rehabilitation Medicine, University of Nottingham, Arkwright House, Derby City Hospital, Derby, UK, DE22 3NE. margaret.phillips@nottingham.ac.uk
Margaret F
MF
Phillips
Rosaline
R
Quinlivan
D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004110:Diltiazem / Q000627:therapeutic use; D005444:Flunarizine / Q000627:therapeutic use; D006801:Humans; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy*; D009543:Nifedipine / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D014700:Verapamil / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D005444:Flunarizine