title: Nocturnal leg cramps and prescription use that precedes them: a sequence symmetry analysis.
abstract: BACKGROUND
  The use of diuretics, statins, and inhaled long-acting β2-agonists (LABAs) is linked to muscle cramps but largely by anecdotal evidence. This study sought population-level data to better evaluate these associations.
  
  
  METHODS
  Linked health care databases containing prescribing information (December 1, 2000, to November 30, 2008) about 4.2 million residents of British Columbia, Canada, were evaluated using sequence symmetry analysis to determine in adults 50 years or older whether new quinine prescriptions (initiations of cramp treatment) increase in the year following diuretic, statin, or LABA starts. The statistic of interest was the sequence ratio: the number of quinine starts in the year following index drug introduction compared with the number of quinine starts in the preceding year (adjusted for age and time trends in population prescribing).
  
  
  RESULTS
  Adjusted sequence ratios (95% CIs) for the 3 drug classes were 1.47 (1.33-1.63 [P < .001]) for diuretics, 1.16 (1.04-1.29 [P = .004]) for statins, and 2.42 (2.02-2.89 [P < .001]) for LABAs. For diuretic subclasses, adjusted sequence ratios (95% CIs) were 2.12 (1.61-2.78 [P < .001]) for potassium sparing, 1.48 (1.29-1.68 [P < .001]) for thiazidelike, and 1.20 (1.00-1.44 [P = .07]) for loop. For LABA subclasses, adjusted sequence ratios (95% CIs) were 2.17 (1.56-3.02) for LABAs alone and 2.55 (2.06-3.12) for LABAs-corticosteroids (P < .001 for both).
  
  
  CONCLUSIONS
  Cramp treatment was substantially more likely in the year following introduction of LABAs, potassium-sparing diuretics, or thiazidelike diuretics, and 60.3% of quinine users (individuals experiencing cramp) received at least 1 of these medications during a 13-year period. In contrast, statin and loop diuretic associations were small. Physicians should be mindful that the use of these medications may worsen symptoms in patients experiencing nocturnal leg cramps.
authors.affiliation: Therapeutics Initiative, University of British Columbia, Vancouver, BC V6T 1Z3, Canada. scott.garrison@ti.ubc.ca
authors.forename: Scott R
authors.initials: SR
authors.lastname: Garrison
authors.forename: Colin R
authors.initials: CR
authors.lastname: Dormuth
authors.forename: Richard L
authors.initials: RL
authors.lastname: Morrow
authors.forename: Greg A
authors.initials: GA
authors.lastname: Carney
authors.forename: Karim M
authors.initials: KM
authors.lastname: Khan
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects; D002170:Canada / Q000453:epidemiology; D015986:Confounding Factors, Epidemiologic; D016208:Databases, Factual; D011307:Drug Prescriptions / Q000706:statistics & numerical data*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009120:Muscle Cramp / Q000139:chemically induced* / Q000188:drug therapy / Q000453:epidemiology; D009125:Muscle Relaxants, Central / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011803:Quinine / Q000627:therapeutic use; D020922:Sleep-Wake Transition Disorders / Q000139:chemically induced* / Q000188:drug therapy / Q000453:epidemiology; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000318:Adrenergic beta-Agonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009125:Muscle Relaxants, Central; D026941:Sodium Channel Blockers; D049993:Sodium Chloride Symporter Inhibitors; D049994:Sodium Potassium Chloride Symporter Inhibitors; D011803:Quinine