Evidence-Based Reviews

Antipsychotics in dementia: Beyond ‘black-box’ warnings

Current Psychiatry. 2008 June;7(6):51-65

References

1. Jeste DV, Meeks TW, Kim DS, Zubenko GS. Research agenda for DSM-V: diagnostic categories and criteria for neuropsychiatry syndromes in dementia. J Geriatr Psychiatry Neurol 2006;19:160-71.

2. Yaffe K, Fox P, Newcomer R, et al. Patient and caregiver characteristics and nursing home placement in patients with dementia. JAMA 2002;287:2090-7.

3. Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry 2006;14:191-210.

4. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA 2005;294:1934-43.

5. Jeste DV, Blazer D, Casey D, et al. ACNP White Paper: update on the use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology 2008;33(5):957-70.

6. Nasrallah HA, White T, Nasrallah AT. Lower mortality in geriatric patients receiving risperidone and olanzapine versus haloperidol: preliminary analysis of retrospective data. Am J Geriatr Psychiatry 2004;12:437-9.

7. Schneeweiss S, Setoguchi S, Brookhart A, et al. Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients. CMAJ 2007;176:627-32.

8. Wang PS, Schneeweiss S, Avorn J, et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med 2005;353:2335-41.

9. Trifirò G, Verhamme KM, Ziere G, et al. All-cause mortality associated with atypical and typical antipsychotics in demented outpatients. Pharmacoepidemiol Drug Saf 2007;16:538-44.

10. Gill SS, Bronskill SE, Normand SL, et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med 2007;146:775-86.

11. Kales HC, Valenstein M, Kim HM, et al. Mortality risk in patients with dementia treated with antipsychotics versus other psychiatric medications. Am J Psychiatry 2007;164:1568-76.

12. Gill SS, Rochon PA, Herrmann N, et al. Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study. BMJ 2005;330:445.-

13. Liperoti R, Gambassi G, Lapane KL, et al. Cerebrovascular events among elderly nursing home patients treated with conventional or atypical antipsychotics. J Clin Psychiatry 2005;66:1090-6.

14. Jeste DV, Lacro JP, Nguyen HA, et al. Lower incidence of tardive dyskinesia with risperidone versus haloperidol. J Am Geriatr Soc 1999;47:716-9.

15. Rainer M, Haushofer M, Pfolz H, et al. Quetiapine versus risperidone in elderly patients with behavioural and psychological symptoms of dementia: efficacy, safety and cognitive function. Eur Psychiatry 2007;22:395-403.

16. Holmes C, Wilkinson D, Dean C, et al. Risperidone and rivastigmine and agitated behaviour in severe Alzheimer’s disease: a randomised double blind placebo controlled study. Int J Geriatr Psychiatry 2007;22:380-1.

17. Pollock BG, Mulsant BH, Rosen J, et al. A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia. Am J Geriatr Psychiatry 2007;15:942-52.

18. Zhong KX, Tariot PN, Mintzer J, et al. Quetiapine to treat agitation in dementia: a randomized, double-blind, placebo-controlled study. Curr Alzheimer Res 2007;4:81-93.

19. Mintzer JE, Tune LE, Breder CD, et al. Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses. Am J Geriatr Psychiatry 2007;15:918-31.

20. Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med 2006;355:1525-38.

21. Pollock BG, Mulsant BH, Rosen J, et al. A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia. Am J Geriatr Psychiatry 2007;15:942-52.

22. Livingston G, Johnston K, Katona C, et al. Systematic review of psychological approaches to the management of neuropsychiatric symptoms of dementia. Am J Psychiatry 2005;162:1996-2021.

23. Jeste D, Meeks T. To prescribe or not to prescribe? Atypical antipsychotic drugs in patients with dementia. South Med J 2007;100:961-3.

24. Cohen-Mansfield J. Nonpharmacologic interventions for inappropriate behaviors in dementia: a review and critique. Am J Geriatr Psychiatry 2001;9:361-81.

Table 4

Atypicals in dementia: Starting and target doses

Drug	Starting dose	Target dose
Aripiprazole	2.5 to 5 mg/d	7.5 to 12.5 mg/d
Olanzapine	2.5 to 5 mg/d	5 to 10 mg/d
Quetiapine	12.5 to 25 mg/d	50 to 200 mg/d
Risperidone	0.25 to 0.5 mg/d	0.5 to 1.5 mg/d
Source: Reference 23

Related resources

Jeste DV, Blazer D, Casey D, et al. ACNP White Paper: update on use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology 2008;33(5):957-70.
American Association for Geriatric Psychiatry position statement: principles of care for persons with dementia resulting from Alzheimer disease. www.aagponline.org/prof/position_caredmnalz.asp.

Drug brand names

Alprazolam • Xanax
Aripiprazole • Abilify
Atenolol • Tenormin
Buspirone • Buspar
Carbamazepine • Tegretol
Ciprofloxacin • Ciloxan
Citalopram • Celexa
Clozapine • Clozaril
Diphenhydramine • Benadryl
Divalproex • Depakote
Donepezil • Aricept
Haloperidol • Haldol
Hydrocodone/acetaminophen • Lortab, Vicodin
Lorazepam • Ativan
Memantine • Namenda
Olanzapine • Zyprexa
Oxazepam • Serax
Oxybutynin • Ditropan
Paroxetine • Paxil
Quetiapine • Seroquel
Risperidone • Risperdal
Rivastigmine • Exelon
Sertraline • Zoloft
Trazodone • Desyrel
Ziprasidone • Geodon

Disclosure

Dr. Meeks receives research/grant support from the John A. Hartford Foundation, the Mental Health Research Foundation, NARSAD, and the U.S. Department of Health and Human Services’ Health Resources and Services Administration.

Dr. Jeste receives research/grant support from the John A. Hartford Foundation, the National Institute of Aging, and the National Institute of Mental Health. AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, and Janssen, L.P. provide free medications for an NIMH-funded study for which Dr. Jeste is the principal investigator.