Current issues of ACP Journal Club are published in Annals of Internal Medicine


Second-generation antipsychotics did not improve outcomes and increased costs for patients with Alzheimer disease and psychosis


ACP J Club. 2008 Mar-Apr;148:53. doi:10.7326/ACPJC-2008-148-2-053

Clinical Impact Ratings

GIM/FP/GP: 5 stars

Hospitalists: 6 stars

Geriatrics: 6 stars

Neurology: 5 stars

Source Citation

Rosenheck RA, Leslie DL, Sindelar JL, et al. Cost-benefit analysis of second-generation antipsychotics and placebo in a randomized trial of the treatment of psychosis and aggression in Alzheimer disease. Arch Gen Psychiatry. 2007;64:1259-68. [PubMed ID: 17984395]



Do second-generation antipsychotics improve health and reduce costs in patients with psychosis and Alzheimer disease (AD)?


Design: Cost–benefit analysis from a randomized placebo-controlled trial (Clinical Antipsychotic Trial of Intervention Effectiveness—AD, [CATIE-AD]) with 9-month follow-up.

Setting: 42 clinical sites in the United States.

Patients: 421 ambulatory outpatients (mean age 78 y, 56% women) who had dementia (Alzheimer type) and clinically severe delusions, hallucinations, aggression, or agitation after onset of dementia; lived at home or in assisted living; scored 5 to 26 on the Mini-Mental State Examination and “moderate” or greater on the Neuropsychiatric Inventory (delusion, hallucination, agitation, or “aberrant motor behavior” items) and Brief Psychiatric Rating Scale (≤ 1 wk before randomization); and had a partner or caregiver (≥ 8 h/wk for ≥ 3 d/wk) able to contribute to assessments. Exclusion criteria included schizophrenia; schizoaffective disorder; delirium; probable vascular dementia; and concurrent use of antipsychotics, antidepressants, anticonvulsants as mood stabilizers, or benzodiazepines.

Intervention: Olanzapine (n = 100), quetiapine (n = 94), risperidone (n = 85), or placebo (n = 142), with flexible dosing schedules. If a treatment was discontinued, patients could be re-randomized to 1 of the other 2 drugs or citalopram.

Outcomes: Health care costs; quality-adjusted life-years (QALYs) assessed using the Health Utilities Index Mark 3; and scores on the AD Related Quality of Life (ADRQOL), AD Cooperative Study Activities of Daily Living (ADCS-ADL), and AD dependence scales. Net health benefits were calculated using estimates of $50 000 and $100 000 per QALY/y minus health care costs.

Main results

Adjusted monthly costs over 9 months were lower for placebo as the initial treatment than for olanzapine, quetiapine, or risperidone (P = 0.02). Placebo was better than olanzapine for activities of daily living; groups did not differ for other outcomes (Table) or for net health benefits of treatment at an estimated value of $50 000 or $100 000 per QALY.


In patients with Alzheimer disease and psychosis, olanzapine, quetiapine, and risperidone did not improve outcomes and increased the costs of care.

Source of funding: National Institute of Mental Health.

For correspondence: Dr. R.A. Rosenheck, VA Connecticut Health Care System, West Haven, CT, USA. E-mail

Table. Antipsychotics vs placebo over 9 months in patients with Alzheimer disease (AD) and psychosis or aggression*

Outcomes † Initial treatment (adjusted mean scores) P value
Olanzapine Risperidone Quetiapine Placebo
QALYs 0.12 0.16 0.15 0.14 0.42
ADRQOL 72.44 71.08 72.19 72.12 0.88
ADCS-ADL 30.4 33.27 33.79 34.4 0.03‡
AD dependence 3.73 3.69 3.7 3.62 0.66

*ADCS-ADL = AD Cooperative Study Activities of Daily Living scale; ADRQOL = AD-Related Quality of Life scale; QALY = quality-adjusted life-year.
†Higher scores better for all scales except AD dependence.
‡Favors placebo compared with olanzapine.


Behavioral and psychological symptoms of dementia (BPSD) are common and challenging to manage. Atypical antipsychotics are frequently prescribed for BPSD, although a recent large, randomized, controlled trial (1) adds to the growing literature that efficacy may be outweighed by adverse effects. Accordingly, the findings of Rosenheck and colleagues, that atypical antipsychotics are not a cost-effective intervention for community-dwelling older adults with AD and significant BPSD, are not surprising.

Although their analysis provides important information about direct health care expenditures, potential indirect costs and benefits were not measured. Management of BPSD accounts for a substantial proportion of all costs associated with dementia care (2), much of which is related to indirect costs of informal caregiver activities provided by family members (3).

Some trials of psychosocial interventions for dementia (4) have shown both efficacy and cost-effectiveness; guidelines and education on alternative management strategies for BPSD are needed. Guidelines should emphasize nonpharmacologic approaches as initial interventions for BPSD when possible (5), and clinicians should minimize use of antipsychotics.

Dallas P. Seitz, MD
Queen's University
Kingston, Ontario, Canada

Andrea Gruneir, PhD
Paula A. Rochon, MD, MPH
University of Toronto
Toronto, Ontario, Canada


1. Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. N Eng J Med. 2006;355:1525-38. [PubMed ID: 17035647]

2. Beeri MS, Werner P, Davidson M, Noy S. The cost of behavioral and psychological symptoms of dementia (BPSD) in community dwelling Alzheimer's disease patients. Int J Geriatr Psychiatry. 2002;17:403-8. [PubMed ID: 11994927]

3. Harrow BS, Mahoney DF, Mendelsohn AB, et al. Variation in cost of informal caregiving and formal-service use for people with Alzheimer's disease. Am J Alzheimers Dis Other Demen. 2004;19:299-308. [PubMed ID: 15553986]

4. Nichols LO, Chang C, Lummus A, et al. The cost-effectiveness of a behavior intervention with caregivers of patients with Alzheimer's disease. J Am Geriatr Soc. 2007;[Online Early Articles]:doi:10.1111/j.1532-5415.2007.01569.x.

5. Sink KM, Holden KF, Yaffe K. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA. 2005;293:596-608. [PubMed ID: 15687315]