BMJ  2005;330:874 (16 April), doi:10.1136/bmj.38369.459988.8F (published 18 February 2005)

Paper

Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial

Clive Ballard, professor of age related diseases1, Marisa Margallo-Lana, senior lecturer in old age psychiatry1, Edmund Juszczak, senior medical statistician2, Simon Douglas, research nurse3, Alan Swann, consultant in old age psychiatry3, Alan Thomas, consultant in old age psychiatry3, John O'Brien, professor of old age psychiatry3, Anna Everratt, psychology assistant3, Stuart Sadler, psychology assistant3, Clare Maddison, psychology assistant3, Lesley Lee, research nurse3, Carol Bannister, consultant in old age psychiatry4, Ruth Elvish, psychology assistant3, Robin Jacoby, professor of old age psychiatry5

1 Institute of Psychiatry, King's College, London SE5 8AF, 2 Centre for Statistics in Medicine, Oxford University, Oxford OX3 7LF, 3 University of Newcastle, Institute of Ageing, Newcastle General Hospital, Newcastle upon Tyne NE4 4BE, 4 Oxfordshire Mental Healthcare NHS Trust, Fiennes Unit, Horton Hospital, Banbury OX16 9BF, 5 Oxford University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX

Correspondence to: R Jacoby Robin.Jacoby{at}psych.ox.ac.uk

Objectives To determine the respective efficacy of quetiapine and rivastigmine for agitation in people with dementia in institutional care and to evaluate these treatments with respect to change in cognitive performance.

Design Randomised double blind (clinician, patient, outcomes assessor) placebo controlled trial.

Setting Care facilities in the north east of England.

Participants 93 patients with Alzheimer's disease, dementia, and clinically significant agitation.

Intervention Atypical antipsychotic (quetiapine), cholinesterase inhibitor (rivastigmine), or placebo (double dummy).

Main outcome measures Agitation (Cohen-Mansfield agitation inventory) and cognition (severe impairment battery) at baseline and at six weeks and 26 weeks. The primary outcome was agitation inventory at six weeks.

Results 31 patients were randomised to each group, and 80 (86%) started treatment (25 rivastigmine, 26 quetiapine, 29 placebo), of whom 71 (89%) tolerated the maximum protocol dose (22 rivastigmine, 23 quetiapine, 26 placebo). Compared with placebo, neither group showed significant differences in improvement on the agitation inventory either at six weeks or 26 weeks. Fifty six patients scored > 10 on the severe impairment battery at baseline, 46 (82%) of whom were included in the analysis at six week follow up (14 rivastigmine, 14 quetiapine, 18 placebo). For quetiapine the change in severe impairment battery score from baseline was estimated as an average of –14.6 points (95% confidence interval –25.3 to –4.0) lower (that is, worse) than in the placebo group at six weeks (P = 0.009) and –15.4 points (–27.0 to –3.8) lower at 26 weeks (P = 0.01). The corresponding changes with rivastigmine were –3.5 points (–13.1 to 6.2) lower at six weeks (P = 0.5) and –7.5 points (–21.0 to 6.0) lower at 26 weeks (P = 0.3).

Conclusions Neither quetiapine nor rivastigmine are effective in the treatment of agitation in people with dementia in institutional care. Compared with placebo, quetiapine is associated with significantly greater cognitive decline.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to StumbleUpon StumbleUpon   Add to Technorati Technorati    What's this?

Relevant Articles

Quetiapine and rivastigmine may not work for dementia
BMJ 2005 330: 0. [Full Text]

Drugs for Alzheimer's disease and related dementias
Serge Gauthier
BMJ 2005 330: 857-858. [Extract] [Full Text] [PDF]

Quality of care in private sector and NHS facilities for people with dementia: cross sectional survey
Clive Ballard, Jane Fossey, Ramilgan Chithramohan, Robert Howard, Alistair Burns, Peter Thompson, George Tadros, and Andrew Fairbairn
BMJ 2001 323: 426-427. [Extract] [Full Text] [PDF]

Treating behavioural and psychological signs in Alzheimer's disease
Clive Ballard and John O'Brien
BMJ 1999 319: 138-139. [Extract] [Full Text] [PDF]

Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up
Rupert McShane, Janet Keene, Kathy Gedling, Christopher Fairburn, Robin Jacoby, and Tony Hope
BMJ 1997 314: 266. [Abstract] [Full Text]

Survey of neuroleptic prescribing in residents of nursing homes in Glasgow
Alice M McGrath and Graham A Jackson
BMJ 1996 312: 611-612. [Extract] [Full Text]

This article has been cited by other articles:

  • Jalbert, J. J., Daiello, L. A., Lapane, K. L. (2008). Dementia of the Alzheimer Type. Epidemiol Rev 30: 15-34 [Abstract] [Full text]  
  • Wood-Mitchell, A., James, I. A., Waterworth, A., Swann, A., Ballard, C. (2008). Factors influencing the prescribing of medications by old age psychiatrists for behavioural and psychological symptoms of dementia: a qualitative study. Age Ageing 37: 547-552 [Abstract] [Full text]  
  • Qaseem, A., Snow, V., Cross, J. T. Jr., Forciea, M. A., Hopkins, R. Jr., Shekelle, P., Adelman, A., Mehr, D., Schellhase, K., Campos-Outcalt, D., Santaguida, P., Owens, D. K., the Joint American College of Physicians/American, (2008). Current Pharmacologic Treatment of Dementia: A Clinical Practice Guideline from the American College of Physicians and the American Academy of Family Physicians. ANN INTERN MED 148: 370-378 [Abstract] [Full text]  
  • Raina, P., Santaguida, P., Ismaila, A., Patterson, C., Cowan, D., Levine, M., Booker, L., Oremus, M. (2008). Effectiveness of Cholinesterase Inhibitors and Memantine for Treating Dementia: Evidence Review for a Clinical Practice Guideline. ANN INTERN MED 148: 379-397 [Abstract] [Full text]  
  • (2007). How safe are antipsychotics in dementia?. DTB 45: 81-85 [Abstract] [Full text]  
  • Howard, R. J., Juszczak, E., Ballard, C. G., Bentham, P., Brown, R. G., Bullock, R., Burns, A. S., Holmes, C., Jacoby, R., Johnson, T., Knapp, M., Lindesay, J., O'Brien, J. T., Wilcock, G., Katona, C., Jones, R. W., DeCesare, J., Rodger, M., the CALM-AD Trial Group, (2007). Donepezil for the Treatment of Agitation in Alzheimer's Disease. NEJM 357: 1382-1392 [Abstract] [Full text]  
  • Kurlan, R., Cummings, J., Raman, R., Thal, L., For the Alzheimer's Disease Cooperative Study Grou, (2007). Quetiapine for agitation or psychosis in patients with dementia and parkinsonism. Neurology 68: 1356-1363 [Abstract] [Full text]  
  • Blaszczyk, A. T., Mathys, M. (2007). Treatment of Cognitive Decline and Psychiatric Disturbances Associated With Alzheimer's Dementia. Journal of Pharmacy Practice 20: 13-28 [Abstract]  
  • Beier, M. T. (2007). Pharmacotherapy for behavioral and psychological symptoms of dementia in the elderly. Am J Health Syst Pharm 64: S9-S17 [Abstract] [Full text]  
  • Livingston, G, Walker, A E, Katona, C L E, Cooper, C (2007). Antipsychotics and cognitive decline in Alzheimer's disease: the LASER-Alzheimer's disease longitudinal study. J. Neurol. Neurosurg. Psychiatry 78: 25-29 [Abstract] [Full text]  
  • Friedman, J. H. (2006). Atypical antipsychotics in the elderly with Parkinson disease and the "black box" warning.. Neurology 67: 564-566 [Abstract] [Full text]  
  • Gill, S., Marras, C., Anderson, G. M., Lee, P. E., Gurwitz, J. H., Rochon, P. A. (2006). Atypical Antipsychotics Have Very Different Adverse Effect Profiles and Should Not Be Lumped Together--Reply. Arch Intern Med 166: 586-587 [Full text]  
  • Aupperle, P. (2006). Management of aggression, agitation, and psychosis in dementia: Focus on atypical antipsychotics. AM J ALZHEIMERS DIS OTHER DEMEN 21: 101-108 [Abstract]  
  • Schneider, L. S., Dagerman, K. S., Insel, P. (2005). Risk of Death With Atypical Antipsychotic Drug Treatment for Dementia: Meta-analysis of Randomized Placebo-Controlled Trials. JAMA 294: 1934-1943 [Abstract] [Full text]  
  • (2005). Which Drugs (or None) for Alzheimer Disease?. Journal Watch Dermatology 2005: 9-9 [Full text]  
  • (2005). Which Drugs (or None) for Alzheimer Disease?. JWatch General 2005: 1-1 [Full text]  
  • Gauthier, S. (2005). Drugs for Alzheimer's disease and related dementias. BMJ 330: 857-858 [Full text]  

Rapid Responses:

Read all Rapid Responses

correction: this could be low DHEA...
James M. Howard
bmj.com, 18 Feb 2005 [Full text]
Cognitive changes could be explained by reversible acute sedative effects
Erick H Turner
bmj.com, 20 Feb 2005 [Full text]
Agitation in patients with dementia
Zafeer H.K Barki
bmj.com, 9 Mar 2005 [Full text]
Quetiapine for Lewy Body
B. Andrew Farah
bmj.com, 14 Mar 2005 [Full text]
Safety and efficacy of atypical antipsychotics in the treatment of patients with behavioural symptoms of dementia
Peter Paul De Deyn
bmj.com, 17 Mar 2005 [Full text]
The Cognitive Decline Associated with Quetiapine in Alzheimer’s disease
ARUNRAJ BALAKRISHNA KAIMAL, MRCPsych, et al.
bmj.com, 12 Apr 2005 [Full text]
Quetiapine and cognitive decline: apply caution
Ajit K Shah
bmj.com, 16 Apr 2005 [Full text]
Mechanisms of cognitive decline
Simon R Wright
bmj.com, 19 Apr 2005 [Full text]
Confusion around the scales and interpretation of the results
Thomas Marshall
bmj.com, 21 Apr 2005 [Full text]
Conclusion based on insufficient power
Lena Palaniyappan, et al.
bmj.com, 6 May 2005 [Full text]
Rivastigmine - thoughts of a journal club
Jonathan C Haynes, et al.
bmj.com, 9 May 2005 [Full text]
Concerns regarding the article
JANAKIRAMAN RAGURAMAN
bmj.com, 23 Aug 2005 [Full text]
Access jobs at BMJ Careers
Whats new online at Student BMJ