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Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review

BMJ 2004; 329 doi: (Published 08 July 2004) Cite this as: BMJ 2004;329:75
  1. Philip E Lee, behavioural neurology fellow1 (pelee{at},
  2. Sudeep S Gill, adjunct scientist and geriatrician2,
  3. Morris Freedman, behavioural neurologist3,
  4. Susan E Bronskill, scientist2,
  5. Michael P Hillmer, doctoral candidate4,
  6. Paula A Rochon, senior scientist and assistant director4
  1. 1 Rotman Research Institute, Baycrest Centre for Geriatric Care, 3560 Bathurst Street, Toronto, ON, Canada M6A 2E1
  2. 2 Institute for Clinical Evaluative Sciences (ICES), 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5
  3. 3 Department of Medicine (Neurology), University of Toronto, 190 Elizabeth Street, Toronto, ON, Canada M5G 2C4
  4. 4 Kunin-Lunenfeld Applied Research Unit (KLARU), Baycrest Centre for Geriatric Care
  1. Correspondence to: P Lee
  • Accepted 29 April 2004


Objective To review the role of oral atypical antipsychotic drugs in the management of the behavioural and psychological symptoms of dementia (BPSD).

Data sources Medline, Embase, and the Cochrane Library. Reference lists were reviewed and experts were contacted to identify additional trials.

Study selection Double blind randomised controlled trials that evaluated the four oral atypical antipsychotic therapies for BPSD.

Review methods Two reviewers assessed trial validity independently.

Data extraction Demographics of patients, study duration, dose of antipsychotic, primary end points, adverse events.

Results 77 abstracts were reviewed. Five randomised trials (1570 patients) evaluating risperidone and olanzapine were identified. The quality of trials was generally good. Most participants were in an institution (> 96%), elderly (weighted mean 82.3 years), and had Alzheimer's disease (76.3%). Trials lasted 6-12 weeks. Treatment with atypical antipsychotic drugs was superior to placebo for the primary end point in three of the five trials. Two trials comparing risperidone with haloperidol did not find any differences in the primary measures of efficacy. Adverse events were common and included extrapyramidal symptoms, somnolence, and abnormal gait.

Conclusions Although atypical antipsychotic drugs are being used with increasing frequency, few randomised trials have evaluated their use for BPSD. Limited evidence supports the perception of improved efficacy and adverse event profiles compared with typical antipsychotic drugs.


  • We thank Kathy Sykora, Walter Wodchis, and Kenneth Shulman for their suggestions regarding the manuscript revisions. We also acknowledge theexpert assistance of Monica Lee and Susan Garfinkel in the production of this study.

  • Contributors PEL, SSG, and PAR conceived the study, reviewed the literature, and wrote and revised the initial and subsequent drafts. PAR was also overseer of the research network. MF, SEB, and MPH contributed to data analysis and revisions of the manuscript. PEL and SSG are the guarantors.

  • Funding PEL's behavioural neurology fellowship was supported in part by Eli Lilly Canada. SSG was supported by a Canadian Institutes of Health Research (CIHR) Postdoctoral Fellowship. MF was supported by the Saul A Silverman Family Foundation (Toronto, Canada) as part of a Canada-International Scientific Exchange Program (CISEPO) project. PAR was supported by a CIHR Investigator Award. This work was supported by a CIHR operating grant (53124) and a CIHR Chronic Disease New Emerging Team (NET) programme grant (NET 54010). The NET programme receives joint sponsorship from the Canadian Diabetes Association, the Kidney Foundation of Canada, the Heart and Stroke Foundation of Canada, and the CIHR Institutes of Nutrition, Metabolism & Diabetes, and Circulatory & Respiratory Health. SEB was supported in part by New Investigator Award through the NET program.

  • Competing interests MF has received honorariuns from Janssen-Ortho for participating in an advisory board meeting, consulting, and chairing an educational session, and has been supported by Janssen-Ortho to attend conferences. He has also received honorariums from Pfizer and Novartis and has been supported by Pfizer and Novartis to attend conferences.

  • Ethical approval Not required.

  • Accepted 29 April 2004
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