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EDITORIALS: Clive Ballard and John O'Brien Treating behavioural and psychological signs in Alzheimer's disease BMJ 1999; 319: 138-139 [Full text]

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Should acetylcholinesterase inhibitors be tried before neuroleptics?

Tomasz Sobow   (17 July 1999)

Other important issues need to be addressed in further clinical trials

Ajit Shah   (19 July 1999)

Strong agreement with the need for double blind trials.

Richard Gray   (16 August 1999)

Should acetylcholinesterase inhibitors be tried before neuroleptics? 17 July 1999
Tomasz Sobow, MD, PhD, Head of the Psychogeriatric Ward Dep Psychiatry, Medical University Lodz, Poland Send response to journal: Re: Should acetylcholinesterase inhibitors be tried before neuroleptics?	Sir, I have read the article of Dr Ballard with great interest. Indeeed, neuroleptics are usualy drugs of choice in treating behavioural disturbances in demented patients, including AD. Other medications, not mentioned in the editorial, like anticonvulsants, SSRI's and buspirone can also be used in a subset of patients. However, since we can assume that most of behavioural disturbances in demented patient roots from cognitive deficit rather than from psychosis, I believe that cholinergic enhancing therapy may be tried initially, and only when it fails, other mediacations should be used. Donepezil is marketed in Poland for the treatment of cognitive dysfunction in AD of mild to moderate stage. In some cases, however, I have tried the drug in more advanced stages of the disease (always because of the family demand and after appropriate warnings). Surprisingly, there are some cases of responders to such procedure. Even in very severe cases caregivers were able to see an improvement and, what is very interesting, it was not seen in cognitive function but in behavioural symptoms, like pacing, wandering or agitiation (especially during everyday's life activities like bathing). Such response was valuable to caregivers since it alleviated their burden related to care. Moreover, it can be theoretically assumed that the behavioural improvement was related to undetectable cognitive change (so called "floor effect" of cognitive tests is obvious in severe cases). I think that controlled trials of acetylcholinesterase inhibitors for their potential usefulness in more advanced stages of AD is warranted and urgently needed. Potential response predictors should also be identified.
Other important issues need to be addressed in further clinical trials 19 July 1999
Ajit Shah Send response to journal: Re: Other important issues need to be addressed in further clinical trials	Dear Sir, The editorial by Ballard and O'Brien1 illustrating the paucity literature demonstrating efficacy for various pharmacological interventions in the treatment of behavioural and psychological symptoms of Alzheimer's disease is timely. Almost all of the contents of their editorial are equally relevant to all other common dementias seen in everyday clinical practice. They make an important observation pertaining to a high placebo response in extant studies of pharmacological interventions. One important explanation of this is the tendency towards spontaneous decline of behavioural and psychological symptoms of dementia (BPSD) when frequent serial measurements of these features are undertaken. This has been illustrated for some instruments measuring aggressive behaviour in dementia in institutional settings2-4. Most instruments measuring BPSD, semi-structured interviews or rating scales, rely heavily on information from individuals (family carers, nursing staff etc.) other than the patient. Explanations for such tendency to spontaneous decline include: (i) staff completing these instruments may identify and rectify precipitants of BPSD; (ii) staff may choose to under-report such behaviour for fear of criticism or extra work to rectify a problem once identified; and, (iii) serial reporting may lead to reporting fatigue2,4,5. A "run in" period of upto 4 weeks, whilst the instruments are used to measure aggressive behaviour are used, prior to commencement of the intervention to reduce aggressive behaviour has been advocated to reduce these influences in intervention studies2,3. Moreover, the observation that mere formal recording of BPSD can lead to reported reduction of BPSD suggests that non-pharmacological interventions may have an important role in its treatment. Their editorial understandably made limited reference to the paucity studies evaluating non-pharmacological interventions. Nevertheless, this is an important area worthy of further studies not least because side-effects of psychotropic drugs are often troublesome. Clinical trials of pharmacological and non-pharmacological interventions should also address other important issues not featured in the editorial: (i) duration of the intervention before observing efficacy because, in clinical practice, psychiatrists are often expected improve BPSD instantaneously; (ii) in which clinical circumstances should should treatment for BPSD be considered - it may not be necessary to treat BPSD if the patient is not distressed or not causing harm to self or to others (many of the extant studies have had a very low threshold for treating BPSD, which in clinical practice may not require treatment); and, (iii) cost-effectiveness of the interventions as many health authorities are currently reluctant to fund new and novel treatments without economic data. These specific issues, in addition to many of the important issues raised in this very useful editorial, were recently addressed at consensus meeting on BPSD organised by the International Psychogeriatric Association. Yours sincerely, Dr Ajit Shah Consultant Psychiatrist 1. Ballard C, O'Brien J. Treating behavioural and psychological signs of Alzheimer's disease. British Medical Journal. 1999; 319: 138-139. 2. Shah AK. Some methodological issues in using aggression rating scales in intervention studies among institutionalised elderly. International Psychogeriatrics. In Press. 3. Nilsson K, Palmsteirna T, Wistedt B. Aggressive behaviour in hospitalised psychogeriatric patients. Acta Psychiatrica Scandinavica. 1988; 78: 172-175. 4. Shah AK. The necessary characteristics of behavioural and psychological signs and symptoms of dementia rating scales. International Psychogeriatrics. In Press. 5. Shah AK, Allen H. Is improvement possible in the measurement of behavior disturbance in dementia. International Journal of Geriatric Psychiatry. In Press. John Connolly Unit West London Healthcare Trust Uxbridge Road Southhall Middlesex UB1 3EU
Strong agreement with the need for double blind trials. 16 August 1999
Richard Gray, Director of the Birmingham Clinical Trials Unit University of Birmingham Clinical Trials Unit Send response to journal: Re: Strong agreement with the need for double blind trials.	RG.CLL The Editor British Medical Journal BMA House Tavistock Square London WC1H 9JR 16 August 1999 Dear Sir We strongly agree with Ballard and O’Brien1 that ‘There is an urgent need for double blind trials focusing on specific behavioural or psychological signs in dementia….. especially studies using cholinesterase inhibitors’. The national AD2000 trial evaluating the effect of donepezil on clinically meaningful endpoints is precisely such a trial. Wider participation would be welcome. Details are available from the address below. Yours sincerely Richard Gray Peter Bentham Elizabeth Sellwood On behalf of the AD2000 Steering Group University of Birmingham Clinical Trials Unit Institute of Clinical Research Edgbaston Birmingham B15 2TT 1Ballard C, O’Brien J. Treating behavioural and psychological signs in Alzheimer’s disease. The evidence for current pharmacological treatments is not strong. BMJ 1999;319:138-9