Call for guidelines on when to stop or continue drug treatment for Alzheimer’s Disease

Call for guidelines on when to stop or continue drug treatment for Alzheimer’s Disease

Doctors taking part in a survey on Alzheimer’s Disease (AD) management have called for clear and consistent guidelines on diagnosis and treatment of the condition to be drawn up as a matter of urgency.  The survey was sponsored by Eisai Europe Ltd and Pfizer Inc, who market the cholinesterase inhibitor Aricept (donepezil), and was presented during the International Conference on Alzheimer’s Disease and Related Disorders. 

It shows 85 per cent of the 376 participating physicians, consisting mainly of neurologists seeing up to 60 or more AD patients per month, feel there is an urgent need for comprehensive clinical guidelines including criteria for continuing or stopping treatment.  
 

Results of the survey showed many doctors are likely to abandon treatment before it has a chance to work in slow responders.  Only one in 12 waits six months or longer to decide if a drug treatment is working although a recent study shows around one third of patients receiving Aricept (donepezil) take longer than 24 weeks before a measurable improvement in their condition is apparent on the Mini-Mental State Examination (MMSE) cognitive score (1). 

The survey of 376 physicians from over 40 countries shows the vast majority (73 per cent) evaluate treatment response within 3 months and indicates that 34-35 per cent of them would either discontinue treatment altogether or try a different AD medication at that stage if symptoms decline or are merely stabilised.  

Whilst almost all physicians agreed that it is important to assess cognitive, functional and behavioural symptom domains when evaluating the impact of drug therapy, over half of them saw cognitive assessments as being of greater importance in the assessment process rather than improvements in ability to carry out daily living activities or in behavioural symptoms.

The Eisai and Pfizer-funded study AWARE (Aricept Washout and Rechallenge Study) shows some patients are slow to demonstrate a treatment response (1).  Almost a third (31 per cent) of patients with mild to moderate disease receiving Aricept 5-10mg daily for 24 weeks demonstrated uncertain benefit initially.  They were then randomised in a double-blind phase to receive either a further 12 weeks Aricept 10mg/day treatment or placebo.  Those receiving further Aricept showed a significant improvement in cognition and behaviour (p0.01) and a trend to improvement on assessment of functional improvement in activities of daily living. Three quarters treated with Aricept showed improvement or stabilisation across cognition, function and behaviour.  When placebo-treated patients were rechallenged with Aricept, their scores on the MMSE improved to the level that the difference previously noted between scores of the placebo and continuously-treated groups disappeared. 
 

Professor Bengt Winblad, Professor  of Geriatric Medicine at the Karolinska Institute, Stockholm commented:  “Stabilisation of symptoms or a slowing of decline should be considered as treatment benefits.  Its important for physicians to take this into account when carrying out initial treatment evaluations.”  Not showing improvement on the MMSE did not mean that improvement was not evident in other domains but these areas, of huge importance to carers and patients themselves, tend to be overlooked, he added:  “My feeling is that Aricept works in almost all patients.  The problem is that in some people you cant see the benefit until you withdraw treatment and the patient then gets worse.” 

The authors of the AWARE study say:  “A 3-6 month timeframe may be insufficient for a complete assessment of treatment benefits and reliable assessments should therefore include data from at least two timepoints over a period of more than 6 months following treatment initiation.”  They also suggest an integrated assessment across a variety of domains is more reliable when determining treatment success.  In AWARE, clinicians were very clearly biased towards cognition when assessing clinical benefit, they commented.  The clinical reality in many countries is that” treatment for AD is often discontinued if patients decline by a single point on the MMSE,” they added. However, persisting with treatment paid off for patients in the AWARE study. “Treatment benefit with donepezil occurred in at least one domain in more than 90 per cent of the study population during the treatment period.”
  
Reference:

1. Johannsen P, Salmon E, Hampel H et al.  Assessing therapeutic efficacy in a progressive disease:  a study of donepezil in alzheimer’s disease.  CNS Drugs 2006; 20: 311-325.

Olwen Glynn Owen – Pharmiweb Field Reporter