Reducing prescribing of highly anticholinergic antidepressants for elderly people: randomised trial of group versus individual academic detailing
BMJ 2001; 322 doi: https://doi.org/10.1136/bmj.322.7287.654 (Published 17 March 2001) Cite this as: BMJ 2001;322:654All rapid responses
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van Eijk and colleagues refer to extensive literature regarding
antidepressant prescription and its problems in the elderly (1). It is
unfortunate that their classification of antidepressants into "highly" and
"less" anticholinergic categories appears flawed. Radioligand data
provide clear evidence that antidepressants vary enormously in their
ability to antagonize the muscarinic receptor in human brain, providing
the likely mechanism for memory dysfunction and delirium (2). The data
indicate that classical tricyclics are uniformly more potent that other
antidepressants, and it is thus surprising that the authors consider
several tricyclics, including trimipramine, to be "less anticholinergic",
while the tetracyclic maprotiline, with one-tenth the affinity, is
included in the "highly anticholinergic" category.
van Eijk and colleagues' results show that risky prescribing
practices are modifiable. It would be of interest to determine the
clinical impact of such a strategy, either in reducing antimuscarinic
burden, as can be measured in peripheral blood (3), or by decreasing the
rate or severity of cognitive dysfunction. Unfortunately, the latter may
be particularly difficult to demonstrate, because cognitive impairment in
the elderly is often multifactorial, and multiple drugs, not just
antidepressants, may contribute to antimuscarinic toxicity (3-5).
References
1. van Eijk ME, Avorn J, Porsius JA, Boer A. reducing prescribing of
highly anticholinergic antidepressants for elderly people: randomised
trial of group versus individual academic detailing. BMJ 2001;322:654-7.
(17 March)
2. Richelson E, Nelson A. Antagonism by antidepressants of
neurotransmitter receptors of normal human brain in vitro. Journal of
Pharmacology & Experimental Therapeutics 1984;230:94-102.
3. Tune LE. Serum anticholinergic activity levels and delirium in
the elderly. Seminars in Clinical Neuropsychiatry 2000;5:149-53.
4. Moore AR, O'Keeffe ST. Drug-induced cognitive impairment in the
elderly. Drugs & Aging 1999;15:15-28.
5. Gray SL, Lai KV, Larson EB. Drug-induced cognition disorders in
the elderly: incidence, prevention and management. Drug Safety 1999;21:101
-22.
Conflict of interest : none
Competing interests: No competing interests
Dear Sir,
I read van Eijk et al's1 article with interest. One of the commonest
reasons for prescribing tricyclic antidepressants in the elderly in
general practice in the UK is for their sedative effects. Since the
problems of dependence with benzodiazepines many GPs are reluctant to
prescribe that group of drugs to the elderly who complain of sleep
problems. The common belief is that antidepressants are safer.
Unfortunately, the antidepressants that are used for their sedative
effects are highly anticholinergic and also have alpha blocking effects
making them dangerous for the elderly .
To review the extent of this type of prescribing, I examined computer
records of two large multi-partner GP practices in the north of Liverpool.
There was a total of 120 patients who were receiving tricyclic
antidepressants as sedatives. The commonest prescribed drug was
amitryptiline(in 92 cases), followed by Dothiepin(in the rest). Both the
drugs were prescribed in 50 mg dose. The average age of the patients was
82 years, women outnumbered men by 3 to 1. 70% of the patients have been
continuously taking the drugs on repeat prescription for an average of 5
years. The patients were also taking on an average four other classes of
medication.
None of the patients reported any current depressive symptoms or any
past history of depression. All of them agreed that they were given the
tablet for sleep problems. None of the patients were ready to even
consider coming off the tablets.
Sleep problems in the elderly is common and to some extent a symptom
of ageing. Instead of prescribing tricyclic antidepressants, GPs should
first try and explain the physiological change in sleep architecture in
old age and promote good sleep hygiene techniques. Even when medication is
prescribed, it should be reviewed. Long term use of antidepressants(even
in low doses) in the elderly has serious consequences(i.e., confusion,
falls, constipation, hypotension, tardive dyskinesia). Since most elderly
patients are on more than one medication, co-prescribing with tricyclic
antidepressants also increases the risk of adverse drug interaction.
Reference
1. Eijk van ME, Avorn J, Porsius JA, Boer A. reducing prescribing of
highly anticholinergic antidepressants for elderly people: randomised
trial of group versus individual academic detailing. BMJ 2001; 7287: 654-
657(17 March).
Conflict of interest : none
Competing interests: No competing interests
I was disappointed to find that the BMJ continues to publish articles
describing randomised controlled trials of interventions to change human
behaviour. We seem to have reached a position in which the statement
“systematic reviews of rigourous studies provide the best evidence of the
effectiveness of different strategies for promoting behavioural change.”
[1] is accepted without question. We have been mesmerized by the aura of
spurious scientific respectability surrounding the initials “RCT”. The
phrase “hierarchy of evidence” is trotted out on all occasions, with
little or no thought for the true nature and purpose of an RCT.
In the natural sciences, experimenters can be confident that one
sample of calcium carbonate will respond in exactly the same way as any
other when treated in the same way. Chemists therefore only need to
perform their experiments on one sample. When investigating the effects of
drugs on the human body, we cannot make the same assumption. The human
body is complex, and so in order to gain some idea of what the average
effect of a drug will be, we carry out the same test on large numbers of
people. In order to minimize unwanted effects, we make the trial
randomized and, if at all possible, double blind as well. The results give
us statistical information about the probable effects of a particular
drug. We can accept such results because we can assume that if the same
person were given the same drug on several occasions, their body will
respond in the same way. The body cannot choose how to respond to a drug.
When investigating human behaviour, as van Eijk et. al. set out to do, we
can make no such assumption. Human beings can choose how to respond to an
intervention. An educational input which catches my imagination on one
occasion, may not do so on another occasion if I am bored, tired or
emotionally distressed. The effects of an intervention can only be assumed
to hold true on one occasion, with one set of individuals. Randomly
assigning people to different groups will not result in control for all
other factors, as it is impossible to know how what influences an
individuals preferred learning style.
All this is important, because large amounts of time and money are
spent on studies such as this. I agree that it is vital that we try and
understand the process of professional behaviour change. If we are to
obtain useful information we must stop subjecting large groups of
individuals to interventions and assuming that the results obtained will
hold true for totally different individuals – or even the same individuals
at a different point in time, and start asking people about their
responses to interventions. Only by understanding how people learn and
decide how to behave through well-conducted qualitative studies will we
begin to make progress.
1. Bero, L., et al., Getting research findings into practice. Closing
the gap between research and practice: an overview of systematic reviews
of interventions to promote the implementation of research findings.
British Medical Journal, 1998. 317: p. 465.
Competing interests: No competing interests
Responses from the authors
re Dr Checkland's comments: We cannot agree with Dr Checkland that
there is no place for randomised controlled trials in studies of human
behaviour; this assertion would deny the utility of entire branches of the
social sciences! To the contrary, although human actions are certainly
more complex than simple chemical reactions, there is more than ample
evidence that well conducted studies can yield important findings about
the effects of behavioural interventions. Thousands of papers in
psychology and related disciplines confirm this. In fact, it is
irresponsible not to conduct such methodologically sound studies of
behavioural interventions in medicine, since this is the most effective
way of learning what works and what doesn't. We do, however, agree that
qualitative analysis also has an important role to play. In our opinion it
can add to our knowledge on human behaviour, next to quantitative studies.
re Dr Sikdar's comments: Dr. Sikdar is correct that improving sleep
hygiene is a more effective and far safer way to improve sleep than daily
doses of 50 mg amitryptiline in the very old, which as he points out are
more likely to induce a host of CNS side effects. Audits such as the one
he performed are a valuable tool in assessing prescribing quality, and
should be conducted far more often.
re Dr Menkes' comments: We have chosen for a classification in highly
and less anticholinergic antidepressants which is in accordance with other
information GPs in the Netherlands receive. We realised that there is
evidence available in literature to support another classification.
However, as this was primarily a study on human behaviour we did not want
to dilute the effect of our intervention by giving conflicting
information. Next to the intervention described in this article, we also
sent a questionnaire to all 60 plus users of antidepressants. We
experimented dichotomising the data on antidepressant use in several ways,
including receptor affinity, dosage and regimen. This did not increase the
correlations between antidepressant use and complaints, not even of dry
mouth. We agree that evaluation of the clinical impact of our strategy is
of great importance as well.
M.E.C. van Eijk, Martine@van-eyk.net
J. Avorn, JAVORN@partners.org
A.J. Porsius,
A.J.Porsius@pharm.uu.nl
A. de Boer, A.deBoer@pharm.uu.nl
Competing interests: No competing interests