Tools for Practice Outils pour la pratique


#206 Agitation in Dementia: Quantifying the effects of antipsychotics


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

BOTTOM LINE
RÉSULTAT FINAL
 A strong placebo effect explains most of the perceived efficacy, with antipsychotics providing little additional improvement over placebo on agitation scales (~3 additional points out of 144). However, 50% improvement in behaviour occurs in ~46% on antipsychotic versus ~33% on placebo. Harms are serious (increased death or cerebrovascular 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


EVIDENCE
DONNÉES PROBANTES
 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 scale, unlikely 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   
Context: 
  • 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:  
    • In severe aggression if risk to patient/others. Balance benefit versus risk of death and cerebrovascular events.14 
    • Target agitation without sedation.15 

Latest Tools for Practice
Derniers outils pour la pratique
program image
Allison Paige MD CCFP

#364 Facing the Evidence in Acne, Part II: Oral Antibiotics

How effective are oral antibiotics in treating acne of at least mild-moderate severity?
Read Lire 0.25 credits available Crédits disponibles
program image
Bradley LeDrew PharmD candidate

#363 Making a difference in indifference? Medications for apathy in dementia

In patients with dementia, how safe and effective are stimulants, antidepressants, and antipsychotics for treating apathy?
Read Lire 0.25 credits available Crédits disponibles
program image
Allison Paige MD CCFP

#362 Facing the Evidence in Acne, Part I: Oral contraceptives and spironolactone in females

How effective are combined oral contraceptives (COC) and spironolactone for treating acne of at least mild-moderate severity in females?
Read Lire 0.25 credits available Crédits disponibles
February 26, 2018

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

Ce contenu est certifié pour les crédits MainPro+, Ouvrir une session
Author(s)
Auteur(s)
  • 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: https://www.acfp.ca/wp-content/uploads/tools-for-practice/1425325257_tfp133benzosagitationdementiafv.pdf. Last Accessed: October 3, 2017.

13. Allan GM, Behn Smith D. Tools for Practice. Available at: https://www.acfp.ca/wp-content/uploads/tools-for-practice/1397830928_20140408_114248.pdf. Last Accessed: October 3, 2017.

14. Toward Optimized Practice. Cognitive Impairment Clinical Practice Guideline; 2017. Available at: http://www.topalbertadoctors.org/download/2111/Cogn%20Imp%202-Diagnosis%20to%20Management.pdf. 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: https://www.nice.org.uk/guidance/cg42/chapter/1-Guidance. 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.