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

doi:10.1136/bmj.38369.459988.8F

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 quetiapineand rivastigmine for agitation in people with dementia in institutionalcare and to evaluate these treatments with respect to changein cognitive performance.

Design Randomised double blind (clinician, patient, outcomesassessor) 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), cholinesteraseinhibitor (rivastigmine), or placebo (double dummy).

Main outcome measures Agitation (Cohen-Mansfield agitation inventory)and cognition (severe impairment battery) at baseline and atsix weeks and 26 weeks. The primary outcome was agitation inventoryat 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 groupshowed significant differences in improvement on the agitationinventory either at six weeks or 26 weeks. Fifty six patientsscored > 10 on the severe impairment battery at baseline,46 (82%) of whom were included in the analysis at six week followup (14 rivastigmine, 14 quetiapine, 18 placebo). For quetiapinethe change in severe impairment battery score from baselinewas estimated as an average of –14.6 points (95% confidenceinterval –25.3 to –4.0) lower (that is, worse) thanin the placebo group at six weeks (P = 0.009) and –15.4points (–27.0 to –3.8) lower at 26 weeks (P = 0.01).The corresponding changes with rivastigmine were –3.5points (–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 effectivein the treatment of agitation in people with dementia in institutionalcare. Compared with placebo, quetiapine is associated with significantlygreater cognitive decline.

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