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#133 Agitation in Dementia: Are benzos a back-up?


CLINICAL QUESTION
QUESTION CLINIQUE
Are benzodiazepines a reasonable pharmaceutical alternative for management of agitation in demented elders?


BOTTOM LINE
RÉSULTAT FINAL
Many trials are old, most are short and/or small, and the results are inconsistent. Benzodiazepines appear, at best, equivalent to antipsychotics in reducing agitation in the short-term, but superior to placebo. If used, they should be stopped as soon as possible due to potential harms.   



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EVIDENCE
DONNÉES PROBANTES
  • Eight randomized controlled trials (RCTs) comparing benzodiazepines to antipsychotics, placebo, or other drugs: 
    • Diazepam vs. thioridazineThioridazine statistically better.1 
      • Nurses rating of improvement: 70% thioridazine vs. 15% diazepam. Number Needed to Treat (NNT)=2. 
    • Oxazepam vs. haloperidol vs. diphenhydramine:2 No statistical difference but oxazepam worse behavioural scores.  
    • Alprazolam vs. haloperidol:3 Both treatments worse than baseline but no statistical difference 
    • Lorazepam vs. olanzapine vs. placebo:4 Lorazepam 1 mg similar to olanzapine (5 mg and 2.5 mg), and all better than placebo.   
      • 40% improved PANSS-EC (measures agitation) at two hours: Lorazepam 72%, olanzapine 62-67%, placebo 37%. Lorazepam NNT=3.  
    • Diazepam vs. thioridazine vs placebo:5 Diazepam worse than thioridazine but better than placebo on some scales.   
      • One point improvement on one anxiety scale: 65% Diazepam, 77% thioridazine, 42% placebo.   
    • Oxazepam vs. placebo:6 Oxazepam better. 
      • “Moderate improvement clinical response: Oxazepam NNT=2.  
    • Oxazepam vs. placebo:7 Oxazepam better. 
      • “Slight improvement” or better clinical response: Oxazepam NNT=5.  
    • Temazepam vs. lorazepam:8 No statistical difference. 
  • Limitations:1-8 Poor description of methods (randomization unclear, etc.), most short (one day to 12 weeks), small (most ≤100 patients)many >25% loss to follow-up, many industry-funded or unclear, etc.   
  • Harms: Poor reporting of harms. Mild-moderate sedation: Lorazepam (10.3%) vs. olanzapine 5 mg (4.2%) vs. olanzapine 2.5 mg (3%), placebo (3%).4  
Context:   
  • Agitation or behavioural issues are very common (up to 75%) in nursing home patients.9 
  • Benzodiazepines are associated with adverse events like falls (57% relative increase) and fractures (34% relative increase). Other medicines, like antidepressants/antipsychotics, are associated with similar risks of these adverse events.10,11     
  • Guidelines for agitation in dementia vary:9 
    • Some (example British Columbia) discourage benzodiazepines because of adverse events. 
    • Others (example American Psychiatric Association and NICE-UK) suggest considering short-acting benzodiazepines as needed for infrequent agitation.  


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Author(s)
Auteur(s)
  • G. Michael Allan MD CCFP
  • Rita McCracken MD CCFP PhD(student)

1. Covington JS. South Med J. 1975; 68:719-24.

2. Coccaro EF, Kramer E, Zemishlany Z, et al. Am J Psychiatry. 1990; 147:1640-5.

3. Christensen DB, Benfield WR. J Am Geriatr Soc. 1998; 46:620-5.

4. Meehan KM, Wang H, David SR, et al. Neuropsychopharmacology. 2002; 26:494-504.

5. Stotsky B. Clin Ther. 1984; 6:546-59.

6. Beber C. Dis Nerv Syst. 1965; 26:591-5.

7. Sanders JF. Geriatrics. 1965 ;20:739-46.

8. Ancill RJ, Carlyle WW, Liang RA, et al. Int Clin Psychopharmacol 1991; 6:141-6.

9. McIntosh B, Clark M, Spry C. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2011. Available from: http://www.cadth.ca/media/pdf/M0022_Benzodiazepines_in_the_Elderly_L3_e.pdf (Accessed December 8, 2014.)

10. Woolcott JC, Richardson KJ, Wiens MO, et al. Arch Intern Med. 2009; 169:1952-60.

11. Takkouche B, Montes-Martínez A, Gill SS, et al. Drug Saf. 2007; 30:171-84.

Authors do not have any conflicts to disclose.