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

Abstract

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.

• Authors: Clive Ballard, Marisa Margallo-Lana, Edmund Juszczak, Simon Douglas, Alan Swann, Alan Thomas, John O'Brien, Anna Everratt, Stuart Sadler, Clare Maddison, Lesley Lee, Carol Bannister, Ruth Elvish, Robin Jacoby
• Journal: BMJ (Clinical research ed.) (BMJ) Vol. 330 Issue 7496 Pg. 874 (Apr 16 2005) ISSN: 1756-1833 [Electronic] England
• PMID: 15722369 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• Cholinesterase Inhibitors
• Dibenzothiazepines
• Phenylcarbamates
• Quetiapine Fumarate
• Rivastigmine

Topics

• Aged
• Alzheimer Disease (drug therapy, psychology)
• Antipsychotic Agents (adverse effects)
• Cholinesterase Inhibitors (adverse effects)
• Cognition Disorders (chemically induced)
• Dibenzothiazepines (adverse effects)
• Double-Blind Method
• Humans
• Middle Aged
• Phenylcarbamates (adverse effects)
• Psychomotor Agitation (prevention & control)
• Quetiapine Fumarate
• Rivastigmine
• Treatment Failure