#133 Agitation in Dementia: Are benzos a back-up?
CLINICAL QUESTION
Are benzodiazepines a reasonable pharmaceutical alternative for management of agitation in demented elders?
BOTTOM LINE
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
- Eight randomized controlled trials (RCTs) comparing benzodiazepines to antipsychotics, placebo, or other drugs:
- Diazepam vs. thioridazine: Thioridazine 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.
- Diazepam vs. thioridazine: Thioridazine statistically better.1
- 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
- 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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