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Keywords:

  • drug interactions;
  • aged;
  • lithium;
  • diuretics;
  • nonsteroidal anti-inflammatory agents;
  • ACE inhibitors;
  • toxicity;
  • pharmacoepidemiology;
  • nested case-control studies

Objectives: To study the association between hospital admission for lithium toxicity and the use of diuretics, angiotensin-converting enzyme (ACE) inhibitors, and nonsteroidal antiinflammatory drugs (NSAIDs) in the elderly.

Design: Population-based nested case-control study.

Setting: Ontario, Canada.

Participants: Ontario residents aged 66 and older treated with lithium.

Measurements: Estimated relative risk of hospital admission for lithium toxicity.

Results: From January 1992 to December 2001, 10,615 elderly patients continuously receiving lithium were identified, of whom 413 (3.9%) were admitted to the hospital at least once for lithium toxicity. After adjustment for potential confounders, a dramatically increased risk of lithium toxicity was seen within a month of initiating treatment with a loop diuretic (relative risk (RR)=5.5, 95% confidence interval (CI)=1.9–16.1) or an ACE inhibitor (RR=7.6, 95% CI=2.6–22.0). Conversely, neither thiazide diuretics nor NSAIDs were independently associated with a significantly increased risk of hospitalization for lithium toxicity.

Conclusion: The use of loop diuretics or ACE inhibitors significantly increases the risk of hospitalization for lithium toxicity, particularly in naïve recipients.