Quetiapine and rivastigmine and cognitive decline in Alzheimer's Disease: randomised double blind placebo controlled trial
Ballard C, Margallo-Lana M, Juszczak E, et al.;
Commented by , 17 May 2005
Aims
To assess efficacy of quetiapine and rivastigmine against placebo, for agitation in people with Alzheimer's Dementia (AD) in institutional care, and to evaluate their effect on cognitive performance.
Method
Inclusion Criteria
Probable or possible Alzheimer's Disease, age >60, clinically significant agitation for at least 6 weeks, using the Cohen-Mansfield agitation inventory and the Neuropsychiatric Inventory (NPI), and no use of antipsychotics or cholinesterase inhibitors for 4 weeks prior to the study. Patients with very advanced or "unstable" AD were excluded.
Evaluations
Participants were assessed at baseline, 6 and 26 weeks by assessors blind to treatment allocation. Doses of up to 50 mg bd of quetiapine and 6 mg bd of rivastigmine were used.
Results
93 patients were randomised, of whom 80 started treatment. 89 % of these tolerated the maximum protocol dose, 94 % completed the agitation inventory assessment at baseline, 86 % at 6 weeks. Demographic characteristics and stage of dementia were similar across the 3 groups.
There were no significant differences between treatments in the change in agitation inventory scores between baseline/6 weeks and baseline/26 weeks.
56/93 scored >10 on the severe cognitive impairment battery at baseline, 46 repeated this battery again at 6 weeks. The 17 patients on quetiapine scored substantially worse after 6 and 26 weeks than the placebo group; rivastigmine patients were intermediate, ie., scored marginally worse in cognition than placebo.
Dr Seymour's comments
The two main findings of this study were:
- Neither quetiapine nor rivastigmine at the above doses helped agitation in institutionalised patients with dementia
- Quetiapine seemed to worsen cognition
This patient group is notoriously difficult to study, with high drop out rates, and problems with validity and completion rates of rating scales. In these difficult circumstances, the authors have applied an acceptably rigorous approach to conducting a randomised controlled trial, though inevitably their results are open to different interpretation.
McShane has previously published data suggesting neuroleptics impair cognition in patients with dementia (ref. 1), and this study reinforces the message that response to neuroleptics in this patient group needs to be closely monitored.
Behavioural and psychological symptoms in advanced dementia are common and distressing, and doctors are frequently expected to prescribe to try and palliate this distress.
This study focussed on one symptom, agitation, in a particular form of dementia (AD) in institutionalised patients: prescribers therefore should not extrapolate these findings to management in other forms of milder dementia.
The evidence base to guide decisions in this patient group is slim. In practice, doctors can justify trying cognitive enhancers, antidepressants, neuroleptics, benzodiazepines and mood stabilisers in BPSD.
As Professor Serge Gauthier says in an accompanying editorial (ref. 2), "the art of treatment is to use the right drug for the right symptoms at the proper stage of the disease, starting low and going slow".
References
1. McShane R. et al. Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up. British Medical Journal 1997; 314 (7076); 266-70 (Note: Free full text article)
2. Gauthier S. British Medical Journal 2005; 330 (7496); 857-858