Medico-legal implications of drug treatment in dementia: prescribing out of licence

AIMS AND METHOD

There is increasing evidence-based knowledge in the drug treatmentof psychotic and behavioural symptoms in dementia, but drugsdo not possess a formal licence for these indications. Drugcompanies, health authorities, NHS trusts and medical defenceunions were asked for their advice on the medico-legal implicationsfor the prescribing clinician.

RESULTS

Drug companies, health authorities, medical defence unions andNHS trusts are aware of out-of-licence prescribing and leaveultimate accountability with the clinician. A suggested bestpractice is that of obtaining the patient's consent.

CLINICAL IMPLICATIONS

Out-of-licence prescribing for psychotic and behavioural symptomsin dementia is widespread. This patient group may be unableto grant consent. The accountability of individual cliniciansshould be supported by more adequate medico-legal frameworks.

Introduction

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Introduction

Poorly informed prescribing in the elderly is increasingly recognised (Hesse et al, 1993; Aparasu et al, 1998; Fremont, 1999; Gambassi et al, 1999).Its regulation in nursing homes first was addressedin the USA by the introduction of the Omnibus Budget ReconciliationAct (OBRA) 1987 (Institute of Medicine, 1986; Morford, 1988),which stipulated that the prescription of specific psychotropicdrugs in nursing homes must be controlled according to theclinical indications of certain listed conditions (Elon & Pawlson, 1992).No UK equivalent exists but there has beenrecent interest in the role of the pharmacist in the medicationreviews in nursing homes (Furniss et al, 2000). Results fromthis recent study confirmed the inappropriate prescription of medication according to OBRA criteria in 54% cases, in linewith the results of a comparable earlier USA study (Beers et al, 1992).

Guidelines for prescribing in the very elderly are unlikelyto reflect knowledge informed by sufficient research becausedrug treatments are normally patented on the basis of a cohortpopulation younger than 70 years of age, which is significantlyyounger, on average, than the patients under the care of psychogeriatricians(Fremont, 1999).

There is substantial evidence that neuroleptics are of benefitin the treatment of psychotic and behavioural symptoms in dementia (Schneider, 1999). Atypical antipsychotics have recognisedadvantages over conventional antipsychotics, owing to a morefavourable side-effect profile, which is especially relevant in an elderly population (Herrmann, 2001). Risperidone hasbeen studied most extensively to date, but evidence on olanzapineand quetiapine appears promising. Alternative treatments thatare effective and relatively well tolerated include the antidepressantstrazodone and citalopram and the anticonvulsants carbamazepine and valproate (Tariot, 1999). Other useful drugs, supportedby anecdotal evidence, include benzodiazepines, beta-blockersand buspirone and hormonal treatments. There is also recent interest in cholinergic enhancers for directly improving psychoticand behavioural symptoms in dementia (Levy et al, 1999).

No drug treatment, however, is specifically licensed for usein the functional and behavioural symptoms of dementia. Furthermore,drug companies are not permitted to endorse their use for indicationsother than those on the Summary of Product Characteristics(SPC). In practice, the guiding principles of prescribing fornoncognitive manifestations of dementia (i.e. affective, psychoticsymptoms and behavioural disturbance) are extrapolated fromthose applying to the treatment of functional illness in youngerpatients. This gap in information leaves clinicians engagedin the care of the elderly with mental illness less than equippedto justify their practice.

Method

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Method

The pharmaceutical advisors from companies producing commonlyused psychotropic drugs (chlorpromazine, promazine, thioridazine,haloperidol, droperidol, trifluoperazine, sulpiride, flupenthixol,clopixol, risperidone, olanzapine, quetiapine, fluoxetine,sertraline, paroxetine, citalopram, trazodone, valproate, carbamazepine,lithium carbonate, diazepam and lorazepam) were contacted inwriting and asked to comment on the indications of their productand their position with regard to out-of-licence prescribing. Similarly, three Local Authorities' Commissioning Managers forPrescribing and Community Pharmacy (Merton, Sutton & WandsworthHealth Authority, Lambeth, Southwark & Lewisham HealthAuthority and West Sussex Health Authority), four NHS trusts(South West London & St George's Mental Health NHS Trust, South London & Maudsley Mental Health NHS Trust, Epsom HealthcareNHS Trust and Worthing Priority Care NHS Trust) and two medicaldefence unions (Medical Protection Society (MPS) and MedicalDefence Union (MDU)) were asked to comment on their positionon out-of-licence prescribing.

Results

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Results

Reply from drug manufacturers
All drug manufacturers replied and this is a summary of theircomments:

All drug companies confirmed that their products were not licensedfor dementia.
In the case of paroxetine, citalopram, trazodone,sulpiride,flupenthixol, clopixol, quetiapine, valproate andlithium carbonateit was confirmed further that there is noplan to extend thelicence. Chlorpromazine was confirmed as licensed in conditionsthat may occur in dementia but are notspecific to dementia.The out-of-patent product and licenceextension could not be supported on commercial grounds.
Alldrug companies stated that the final prescribing decisionisa matter for the clinician, based on the availability ofothertherapeutic options and a careful assessment of the potentialrisks and benefits.

Reply from the health authorities
Comments were returned by two of the three health authoritiescontacted. The main points in their replies are summarisedas follows:

In an official capacity, health authorities cannot support prescribing outside the licence indication.
Health authorities are awareof the existence of prescribingoutside licence.
Prescribingis ultimately considered as a matter for the individual clinician'sbest judgement and each case should be treated individually.
Clinicians are legally supported by the Bolam Rule, whichstatesthat if a representative body of opinion would haveacted ina like manner then that would be acceptable.
Ifgeneral practitioners have any concerns, they should seekadvicefrom the medical defence unions, whereas hospital doctorshaveto conform additionally to the rules of their employingtrust.

Reply from NHS trusts
Comments were returned by three of the four NHS trusts contacted:

NHS trusts are aware of out-of-licence prescribing.
Out-of-licenceprescribing negates the liability of the manufacturer, shouldharm occur.
Trusts would ‘presumably’ supportclinicians iftheir actions could be demonstrated to be adequatelysupportedby the literature and considered reasonable by theirpeers.
Informed consent from the patient should be soughtwhen prescribing unlicensed medication.
The Drug and TherapeuticCommittees of NHS trusts should auditthemselves, reviewingthe use of medication across the trustand ‘indicating acceptable medications in a normal andacceptable practice’.

Reply from the MDU and the MPS
The MDU and MPS confirmed that:

In law, no medicine can be marketed for human use in the UKwithout a product licence granted by the licensing authority.Licensing arrangements only affect manufacturers, are determinedby the Medicines Act 1968 and are implemented through the MedicinesControl Agency.
Doctors therefore are still free to prescribeunlicensed drugsor use drugs for unlicensed indications.
Non-adherenceto the provision set out in the data sheet canbe justified if the licence indications do not reflect currentknowledge.
The prescriber is vulnerable to claims against him/her fornegligenceand liability.
In prescribing unlicensed drugs,the doctor should obtain consentand tell the patient aboutthe status of the drug.

Discussion

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Discussion

Our survey highlights the ethical and legal difficulties facingthe old age psychiatrist when prescribing in this area. Withthe exception of cognition enhancers, all drugs used in theneuropsychiatric management of dementia are unlicensed forthe specific purpose for which they are used. In the light of increasing research suggesting the efficacy of psychotropicdrugs, especially atypical antipsychotics, we suggest thatclinicians have little option but to prescribe out of licence.Indeed, in the UK clinicians are free to do so and are notbound by the licensing restrictions placed on the drug manufacturers by the Medicines Act 1968. However, clinicians are ultimatelyliable for the consequences of their prescribing, as was clearfrom our results, but we would argue without adequate frameworksfor defence.

The replies from both NHS trusts and medical defence unionsstate that the existing defence for the clinician is the BolamRule (Bolam v. Friern Hospital Management Committee, 1957),scientific evidence and written informed consent from the patient(General Medical Council, 2001). We suggest that all thesecomponents of defence are problematic as follows. First, althoughthere is some evidence for psychotropic drugs in dementia,knowledge is still lacking, especially in the areas of thevery elderly and those with concurrent medical illness, bothof which affect a large proportion of our patients. We believethat the lack of knowledge, guidelines or true consensus inthe profession potentially undermines an individual's defence.Second, obtaining consent is all too often impracticable inpatients with dementia, especially written consent. Discussionabout alternatives, such as assent or vicarious approval bya carer, are unlikely to satisfy legal or moral requirements.This area of clinical and medico-legal vulnerability is notexclusive to the old age psychiatrist, yet the latter is undoubtedlychallenged by the seriously complex issue of having to reconciletreatment and the patients' chronic mental incapacity.

In the interest of elderly care and of the discipline, old age psychiatrists may wish to contribute to the growth of the missing research-based evidence and seek to determine more clearly theacceptable terms of medico-legal accountability in supportof unlicensed practice. In particular, we suggest that frailercohorts older than 70 years of age should be considered forlocal and national audits of efficacy and safety of psychotrophictreatments administered in dementia, and of combinations of these drugs with other commonly encountered medical conditionsin the elderly. Drug companies should also widen the age rangeof their subjects in carrying out Phase II and III trials anddevote specifically adapted titrations and efficacy/safetycontrols to the very elderly. We suggest that this would generatefurther research interest, inform our practice and contributeto the improved standards of care invoked by the recently publishedNational Service Framework for Older People (Department of Health, 2001).Furthermore, although the suggestion of obtaininginformed consent is generally unfeasible, adopting well-foundedguidelines for prescribing would go a long way towards strengtheningthe defence of our practice as we await appropriate extensionof product licences by the drug manufacturers.

References

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