Christopher R. Carpenter, MD, MSc
Which drugs are associated with increased risk for delirium?
Included studies evaluated the association between drugs and delirium in hospital patients or long-term care residents. Outcome was delirium (International Classification of Diseases volume 10 or Diagnostic and Statistical Manual for Mental Disorders [DSM] volumes III, III-R, or IV criteria, or a diagnostic tool validated against those criteria).
MEDLINE, EMBASE/Excerpta Medica, PsycInfo, and Allied and Complementary Medicine (all to Oct 2009); and reference lists were searched for randomized controlled trials (RCTs), prospective cohort studies, and case–control studies. 14 studies (n = 4652, mean age 55 to 89 y) met the selection criteria, including 3 RCTs, 10 prospective cohort studies, and 1 nested case–control study. 7 studies evaluated opioids, 7 benzodiazepines, 4 neuroleptics, 2 antihistamine H1-antagonists, and 1 each evaluated histamine H2-antagonists, dihydropyridines, antimuscarinincs, tricyclic antidepressants, antiparkinson medications, digoxin, steroids, and nonsteroidal antiinflammatory drugs.
Meta-analyses were not done because studies were heterogeneous in populations and methods. 1 RCT found that haloperidol and placebo did not differ for delirium (Table). Using multivariate analysis, 1 cohort study found that neuroleptics and opioids were each associated with increased risk for delirium; another cohort study did not find an association between morphine or fentanyl and delirium (Table). 1 matched case–control study found that benzodiazepines were associated with increased risk for delirium, but opioids, including morphine and fentanyl, were not (Table).
Benzodiazepines may be associated with increased risk for delirium. Insufficient evidence exists to evaluate other drugs.
Risk for delirium associated with drugs and drug classes*
*OR = odds ratio; RCT = randomized controlled trial; RR = risk ratio. High-quality studies, moderate-quality studies evaluating drug classes, and single-drug comparisons evaluated in > 1 moderate-quality study are reported here.
†Cohort and case–control studies used multivariate or matched analyses and were of moderate quality.
‡RRs and ORs > 1 indicate increased risk for delirium associated with drug.
Carpenter CR. Review: Insufficient evidence exists about which drugs are associated with delirium; benzodiazepines may increase risk. Ann Intern Med. ;154:JC6–10. doi: 10.7326/0003-4819-154-12-201106210-02010
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Published: Ann Intern Med. 2011;154(12):JC6-10.
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