Tools for Practice


#38 What are the Risks and Benefits of Stopping Antipsychotics in the Elderly?


CLINICAL QUESTION
In elderly patients, what are the risks and benefits of stopping long-term antipsychotics (initiated for behavioral concerns)?

BOTTOM LINE
In elderly patients on long-term antipsychotics, withdrawal of antipsychotics in four patients may prevent one death at two years. After discontinuation, neuropsychiatric symptoms appear to vary little, although one study suggests stopping after four months can cause one in four more patients to have a relapse of neuropsychiatric symptoms. 


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EVIDENCE
Systematic review1,2 of nine Randomized Controlled Trials (RCTs) of antipsychotic discontinuation reporting a variety of outcomes: 
  • Only 1/9 RCTs3 reported a statistically significant difference in the primary neuropsychiatric outcome. Two highest-quality trials (including the one with a neuropsychiatric change): 
    • ADAD:3 180 patients (mean age 80) whose neuropsychiatric symptoms improved with 16 weeks of open-label risperidone (110 patients) were randomized to switch to placebo (discontinuation) or continue risperidone. 
      • Relapse (on any of four measures) at 16 weeks: Discontinued 60% versus continued 33% (Number Needed to Harm (NNH)=4 with discontinuation). 
      • No difference in deaths (but numbers very low). 
    • DART-AD:4,5 165 patients (mean age 85) on antipsychotics for ≥3 months for behavioural disturbance due to dementia were randomized to continue antipsychotic or switch to placebo (discontinue). 
      • Neuropsychotic outcomes at six months: Eight different scales, none worse with discontinuation.4 
      • Mortality was statistically significantly lower in those discontinuing (29%) versus continuing antipsychotics (54%), Number Needed to Treat (NNT)=4 with discontinuation.5 
Context: 
  • One systematic review6 of 15 RCTs found an increased risk of death with second-generation antipsychotics vs. placebo (NNH=84 at 10-12 weeks). 
  • Four of six large cohort studies7 found that first-generation antipsychotics were associated with a greater risk of death than second-generation antipsychotics, whereas the other two studies found a similar associated risk of death. 
    • As observational data, these studies should be interpreted with caution, but suggest older antipsychotics are not safer than newer agents. 
  • Three systematic reviews of antipsychotics for patients with behavioural issues and psychosis in dementia have found the effects to be: 
    • At best, modest (but statistically significant) improvement in aggression and psychosis8,9 or not statistically different from placebo.10 
    • Countered by statistically significant increase in adverse events including cerebrovascular events.10 
updated jan 19 2018
December 6, 2010

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Author(s):

  • Danièle Behn Smith MD CCFP-EM
  • G. Michael Allan MD CCFP

1. Declercq T, Petrovic M, Azermai M, et al. Cochrane Database Syst Rev. 2013; (3):CD007726.

2. Pan YJ, Wu CS, Gau SSF, et al. Dement Geriatr Cogn Disord. 2014; 37:125-40.

3. Devanand DP, Mintzer J, Schultz SK, et al. N Engl J Med. 2012; 367:1497-507.

4. Ballard C, Lana MM, Theodoulou M, et al. PLoS Med. 2008; 5:e76.

5. Ballard C, Hanney ML, Theodoulou M, et al. Lancet Neurol. 2009; 8:151-7.

6. Schneider LS, Dagerman KS, Insel P. JAMA. 2005; 294:1934-43.

7. Maher AR, Maglione M, Bagley S, et al. JAMA. 2011; 306:1359-69.

8. Yury CA, Fisher JE. Psychother Psychosom. 2007; 76:213-8.

9. Wang J, Yu JT, Wang HF, et al. Neurosurg Psychiatry. 2015; 86:101-9.

10. Ballard C, Waite J. Cochrane Database Syst Rev. 2006; (1):CD003476.

Authors do not have any conflicts of interest to declare.