According to the findings of an observational study, the use of diuretics, statins, and long-acting β2-agonists (LABAs) may promote muscle cramping in older adults.

The authors note that nocturnal leg cramps are common in older people (37-50% prevalence).  Although muscle cramping has been linked to the use of various common medications, the evidence for these associations is weak.  The purpose of their study was to determine whether initiation of diuretics, statins or inhaled LABAs (the three most commonly prescribed medications with a potential association with cramping) was associated with a subsequent increased prescribing of medications to treat muscle cramp.

The research involved linked healthcare databases in British Columbia, containing prescribing information (Dec 2000 to November 2008) on about 4.2 million residents.  Researchers used sequence symmetry analysis to evaluate adults aged >50 years starting prescriptions for quinine (used almost exclusively in Canada to treat nocturnal cramps) and one of the three drug classes within a year of each other, in either order.  This type of analysis is based on the fact that the causal drug will more often be prescribed first, if the first causes a symptom that the second treats (if not then the recipients of both will be equally likely to receive them in either order).  The authors state that this type of analysis helps control for many potential confounders, as it is largely independent of patient characteristics.    

The number of individuals in whom quinine use followed use of the index drug was compared with the number of individuals on whom quinine use preceded use of the index drug.  This gives the sequence ratio – which will be >1 if there is a causal relationship.  The reported sequence ratios were adjusted for age and time trends in population prescribing.

The main findings were as follows:

• The adjusted sequence ratio was 1.47 (95% CI 1.33-1.63; P<0.001]) for diuretics, 1.16 (1.04-1.29; P=0.004) for statins, and 2.42 (2.02-2.89; P<0.001) for LABAs.

• For diuretic subclasses, adjusted sequence ratios were 2.12 (1.61-2.78; P<0.001) for potassium sparing, 1.48 (1.29-1.68; P<0.001) for thiazide-like, and 1.20 (1.00-1.44; P=0.07]) for loop.

• For LABA subclasses, adjusted sequence ratios were 2.17 (1.56-3.02) for LABAs alone and 2.55 (2.06-3.12) for LABAs-corticosteroids (P<0.001 for both).

 
The authors comment that physicians should be aware of the epidemiological association between cramp treatment and the use of LABAs, potassium-sparing diuretics, and thiazide-like diuretics, when evaluating patients experiencing nocturnal leg cramps.