Tools for Practice Outils pour la pratique

#206 Agitation in Dementia: Quantifying the effects of antipsychotics

What are the benefits and harms of antipsychotics for agitation in dementia?

A strong placebo effect explains most of the perceived efficacy, with antipsychotics providing little additional improvement over placebo on agitation scales (~additional points out of 144)However, 50% improvement in behaviour occurs in ~46% on antipsychotic versus ~33% on placebo. Harms are serious (increased death ocerebrovascular events for 1 in ~80, for each over placebo) and common (somnolence or gait troubles 1 in ~10 or 20, for each). Antipsychotics should be reserved for cases of severe aggression and withdrawal attempted as soon as possible.  

CFPCLearn Logo

Reading Tools for Practice Article can earn you MainPro+ Credits

La lecture d'articles d'outils de pratique peut vous permettre de gagner des crédits MainPro+

Join Now S’inscrire maintenant

Already a CFPCLearn Member? Log in

Déjà abonné à CMFCApprendre? Ouvrir une session

Six systematic reviews [5-16 Randomized Controlled Trials (RCTs), 856-5,110 patients], most followed ~10-12 weeks.1-6 Statistically significant unless indicated: 
  • Placebo has large effects.7 Example: 
    • Improves 11-points on 144-point neuropsychiatric scale, a clinically meaningful difference. 
  • Atypical antipsychotics:  
    • Mean improvement over placebo on multiple scales trivial at best:1-3  
      • Example 3-points on 144-point neuropsychiatric scaleunlikely clinically meaningful. 
    • Individual antipsychotics (risperidone,2 olanzapine,2 quetiapine5) found similar. 
      • Exception was improvement on the global change scale of 0.32 points on  7-point scale, likely clinically detectable. 
    • Proportion of patients attaining 50% improvement in scales.4  
      • Example: Risperidone 46% versus 33%, Number Needed to Treat (NNT)=8. 
  • Atypical antipsychotic harms:  
    • Stopping due to adverse events:2 Number Needed to Harm (NNH)=13-39. 
    • Serious harms: Death (NNH=77-84),1,4 cerebrovascular events (NNH=48-104).1,2,4 
    • Mini-Mental Status Exam 0.73 worse (not significant).4 
    • Other:1,2,4 Somnolence (NNH=7-11), gait abnormalities (NNH=11-20), extrapyramidal symptoms (NNH=16-44), and peripheral edema (NNH=20-25). 
  • First generation antipsychotics (example haloperidol) appear to have similar rates of harms but inconsistent benefits.6   
  • Cholinesterase inhibitors, SSRIs, trazodone, and valproate provide no meaningful improvement in agitation.8-11 
    • Benzodiazepines may approach antipsychotics for efficacy in agitation but also have harms.12 
  • Stopping antipsychotics may reduce death (NNT=4 at two years) with little impact on neuropsychiatric symptoms.13 
  • While highlighting harms, guidelines support atypical antipsychotic use:  
    • Isevere aggression if risk to patient/othersBalance benefit versus risk of death and cerebrovascular events.14 
    • Target agitation without sedation.15 

Latest Tools for Practice
Derniers outils pour la pratique

#367 Oral Calcitonin Gene-related Peptide Antagonists: A painfully long name for the acute treatment of migraines

What are the risks and benefits of ubrogepant for the acute treatment of episodic migraines?
Read Lire 0.25 credits available Crédits disponibles

#366 Looking for Closure: Managing simple excisions or wounds efficiently

What are some options for efficiency in wound closure?
Read Lire 0.25 credits available Crédits disponibles

#365 Shrooms for Glooms: Evidence for psilocybin for depression

What are the benefits and harms of psilocybin for treatment-resistant/recurrent depression?
Read Lire 0.25 credits available Crédits disponibles

This content is certified for MainPro+ Credits, log in to access

Ce contenu est certifié pour les crédits MainPro+, Ouvrir une session

  • Joey Ton PharmD
  • Jamil Ramji BSc BSP ACPR
  • G. Michael Allan MD CCFP

1. Ma H, Huang Y, Cong Z, et al. J Alzheimers Dis. 2014; 42(3):915-37.

2. Ballard C, Waite J. Cochrane Database Syst Rev. 2006; 1:CD003476.

3. Yury CA, Fisher JE. Psychother Psychosom. 2007; 76(4):213-8.

4. Schneider LS, Dagerman K, Insel PS. Am J Geriatr Psychiatry. 2006; 14:191-210.

5. Cheung G, Stapelberg J. N Z Med J. 2011; 124:39-50.

6. Lonergan E, Luxenberg J, Colford J. Cochrane Database Syst Rev. 2002; 2:CD002852.

7. Rosenberg PB, Drye LT, Porsteinsson AP, et al. Int Psychogeriatr. 2015; 27:2059-67.

8. Campbell N, Ayub A, Boustani MA, et al. Clin Interv Aging. 2008; 3(4):719-28.

9. Seitz DP, Adunuri N, Gill SS, et al. Cochrane Database Syst Rev. 2011; 2:CD008191.

10. Martinon-Torres G, Fioravanti M, Grimley EJ. Cochrane Database Syst Rev. 2004; 4:CD004990.

11. Lonergan E, Luxenberg J. Cochrane Database Syst Rev. 2009; 3:CD003945.

12. McCracken R, Allan GM. Tools for Practice. Available at: Last Accessed: October 3, 2017.

13. Allan GM, Behn Smith D. Tools for Practice. Available at: Last Accessed: October 3, 2017.

14. Toward Optimized Practice. Cognitive Impairment Clinical Practice Guideline; 2017. Available at: Last Accessed: September 28, 2017.

15. National Institute for Health and Care Excellence. Dementia: supporting people with dementia and their carers in health and social care; 2016. Available at: Last Accessed: September 28, 2017.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.