7
Journal of Intellectual Disability Research doi: 10.1111/j.1365-2788.2005.00723.x volume 49 part 11 pp 858 864 november 2005 © 2005 Blackwell Publishing Ltd 858 Blackwell Science, LtdOxford, UKJIRJournal of Intellectual Disability Research0964-2633Blackwell Publishing Ltd, 200549Original Article C. Haw & J. Stubbs Correspondence: Dr Camilla Haw, Consultant Psychiatrist, St. Andrew’s Hospital, Billing Road, Northampton, NN1 5DG, UK (e-mail: [email protected]). A survey of off-label prescribing for inpatients with mild intellectual disability and mental illness C. Haw & J. Stubbs St. Andrew’s Hospital, Northampton, UK Abstract Background The term ‘off-label prescribing’ refers to the use of a drug outside the terms of its Marketing Authorisation, including prescribing for an unli- censed indication. There have been few reports about off-label prescribing in psychiatry. The aims of the study were to determine the frequency of off-label prescribing of psychotropics for inpatients with mild intellectual disability (ID) and mental illness resident in a large psychiatric hospital, the nature of the off- label clinical indications and details about patient consent and case note documentation of the off-label usage. Methods Cross-sectional survey of inpatients of the ID division of a charitable hospital was carried out. Interviews with consultant psychiatrists about off- label use of psychotropics were also made. Results Of the 56 patients studied, 38 (67.9%) were receiving one or more psychotropic drugs and 26 (46.4%) were receiving at least one off-label psycho- tropic. The most frequently cited off-label indications were: reduction of aggression, arousal and behav- ioural disturbance (14 cases) and mood stabilization of affective disturbance (13). The principle psycho- tropics involved were atypical antipsychotics (17 cases) and mood stabilizers (13). Although in most instances the psychiatrist was aware the drug was being used off-label and had consulted other profes- sionals, in only two (6%) instances had the patient been informed of the off-label usage, largely because the psychiatrist felt they lacked the capacity to under- stand the off-label concept. In most cases the off-label usage had not been documented in the case notes. Conclusions Off-label prescribing is common in patients with comorbid ID and mental disorder. When prescribing off-label, psychiatrists need to con- sider the evidence that the drug is likely to be effective for the unlicensed indication and any risks involved. Where there is limited evidence of benefit a trial of the drug, with clinical monitoring may be indicated. Patients should be fully informed about their medi- cation. However, many patients with ID cannot understand the off-label concept. In some circum- stances psychiatrists may find it helpful to consult other professionals before prescribing off-label. Good case note documentation of the process is important and supports the prescriber. Keywords intellectual disability, mental illness, psychotropics, off-label prescribing, survey, unlicensed indications Introduction Off-label prescribing is a term used to describe the use of a drug outside the terms of its Marketing

A survey of off-label prescribing for inpatients with mild intellectual disability and mental illness

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Page 1: A survey of off-label prescribing for inpatients with mild intellectual disability and mental illness

Journal of Intellectual Disability Research doi 101111j1365-2788200500723x

volume 49 part 11

pp

858

ndash

864 november 2005

copy

2005

Blackwell Publishing Ltd

858

Blackwell Science LtdOxford UKJIRJournal of Intellectual Disability Research0964-2633Blackwell Publishing Ltd 200549Original Article

C Haw amp J Stubbs

Correspondence Dr Camilla Haw Consultant Psychiatrist St Andrewrsquos Hospital Billing Road Northampton NN

1

5

DG UK (e-mail chawstandrewcouk)

A survey of off-label prescribing for inpatients with mild intellectual disability and mental illness

C Haw amp J Stubbs

St Andrewrsquos Hospital Northampton UK

Abstract

Background

The term lsquooff-label prescribingrsquo refers to the use of a drug outside the terms of its Marketing Authorisation including prescribing for an unli-censed indication There have been few reports about off-label prescribing in psychiatry The aims of the study were to determine the frequency of off-label prescribing of psychotropics for inpatients with mild intellectual disability (ID) and mental illness resident in a large psychiatric hospital the nature of the off-label clinical indications and details about patient consent and case note documentation of the off-label usage

Methods

Cross-sectional survey of inpatients of the ID division of a charitable hospital was carried out Interviews with consultant psychiatrists about off-label use of psychotropics were also made

Results

Of the

56

patients studied

38

(

67

9

) were receiving one or more psychotropic drugs and

26

(

46

4

) were receiving at least one off-label psycho-tropic The most frequently cited off-label indications were reduction of aggression arousal and behav-ioural disturbance (

14

cases) and mood stabilization of affective disturbance (

13

) The principle psycho-tropics involved were atypical antipsychotics (

17

cases) and mood stabilizers (

13

) Although in most

instances the psychiatrist was aware the drug was being used off-label and had consulted other profes-sionals in only two (

6

) instances had the patient been informed of the off-label usage largely because the psychiatrist felt they lacked the capacity to under-stand the off-label concept In most cases the off-label usage had not been documented in the case notes

Conclusions

Off-label prescribing is common in patients with comorbid ID and mental disorder When prescribing off-label psychiatrists need to con-sider the evidence that the drug is likely to be effective for the unlicensed indication and any risks involved Where there is limited evidence of benefit a trial of the drug with clinical monitoring may be indicated Patients should be fully informed about their medi-cation However many patients with ID cannot understand the off-label concept In some circum-stances psychiatrists may find it helpful to consult other professionals before prescribing off-label Good case note documentation of the process is important and supports the prescriber

Keywords

intellectual disability mental illness psychotropics off-label prescribing survey unlicensed indications

Introduction

Off-label prescribing is a term used to describe the use of a drug outside the terms of its Marketing

Journal of Intellectual Disability Research

volume 49 part 11 november 2005

C Haw amp J Stubbs bull

A survey of off-label prescribing for inpatients859

copy

2005

Blackwell Publishing Ltd

Journal of Intellectual Disability Research

49

858

ndash

864

Authorisation (previously called a product licence) This includes prescribing for an unlicensed indica-tion and prescribing a dosage in excess of that spec-ified in the Marketing Authorisation and the British National Formulary (BNF) Doctors are free to pre-scribe off-label but prescribing in this way increases their professional responsibility (Henry

1999

) The use of a medicine off-label represents an area of potentially increased risk because the national body that licenses drugs for medicinal use (in the United Kingdom the Medicines and Healthcare products Regulatory Agency) has not examined the risks or benefits of using the drug in these circumstances Should the patient suffer an adverse event from the drug liability would rest with the prescriber (Anon-ymous

1992

) Some off-label usages are so common-place that they are listed in the BNF for example the use of sodium valproate for the treatment of mania in bipolar affective disorder

Quite often the licensed indications for a drug are narrow often restricted to adult patients with one particular diagnosis because it is easier in these cir-cumstances for pharmaceutical companies to carry out clinical trials demonstrating a drugrsquos efficacy It is more difficult for companies to carry out studies on special patient groups such as children and those with intellectual disabilities (ID) or those with severely disturbed mental states or relatively uncom-mon disorders For these groups it may not be pos-sible to recruit sufficient patient numbers to a clinical trial or it may be impossible to obtain informed patient consent to take part in a study Clinicians need to be aware of which prescriptions for medica-tion are off-label They need to weigh up the potential risks and benefits involved but they should not feel deterred from prescribing off-label where this is appropriate Senior clinicians and regulators from a number of European countries and North America regard off-label prescribing as a necessary part of the art of medicine (Healy amp Nutt

1998

)In psychiatry off-label prescribing is common A

postal questionnaire of psychiatrists in southern England found that

65

of respondents had pre-scribed medication off-label within the past month (Lowe-Ponsford amp Baldwin

2000

) In a survey of prescriptions for psychiatric patients in south-east England

7

5

of prescriptions were either for unli-censed indications or for doses which exceeded that stated by the product licence (Douglas-Hall

et al

2001

) We have found that among adult inpatients at a specialist psychiatric hospital

94

of prescriptions for mood stabilisers were off-label (Haw amp Stubbs

2005

)The study was carried out in a

450

-bedded chari-table hospital that provides care for patients of all ages with a wide variety of mental health problems including ID forensic and brain injury The aim of the survey was to establish the extent of off-label psychotropic prescribing for inpatients with ID and mental illness andor personality disorder Other aims were to establish the clinical indications for the off-label drugs to inquire if patients had been informed that medicines were being prescribed off-label and if not the reasons for withholding this information and to ask clinicians about their rationale for prescribing these drugs and if they had consulted others before prescribing off-label

Method

The study was approved by the Hospitalrsquos clinical audit and research committees

The charitable hospital concerned is a large ter-tiary referral centre offering specialist inpatient treatment for a wide variety of mental health prob-lems The survey was conducted in the Adult Unit and the Child and Adolescent Unit of Smyth Divi-sion of the Hospital All patients in this Division suffer with mild or borderline ID and mental illness or personality disorderconduct disorder Many are offenders who have committed a range of offences Patients are under the care of three consultant psy-chiatrists The Adult Unit comprises a medium secure admission ward and two locked wards one a rehabilitation unit The Child and Adolescent Unit comprises three locked wards for patients aged

11

ndash

23

years with ID mental illness and severely chal-lenging behaviour

For each patient JS approached their consultant psychiatrist and obtained consent to carry out a structured interview with the psychiatrist The psy-chiatrist was asked (

1

) the patientrsquos ICD-

10

clinical diagnosis (es) (World Health Organization

1992

) and (

2

) where the patient was prescribed a psycho-tropic drug the indications for its use JS then con-sulted the licensed indications given in the British National Formulary no

48

(BNF British Medical

Journal of Intellectual Disability Research

volume 49 part 11 november 2005

C Haw amp J Stubbs bull

A survey of off-label prescribing for inpatients860

copy

2005

Blackwell Publishing Ltd

Journal of Intellectual Disability Research

49

858

ndash

864

Association and Royal Pharmaceutical Society of Great Britain

2004

) and Medicines Compendium

2004

(Association of the British Pharmaceutical Industry

2004

) to determine whether or not the drug was being used off-label Where it was the psychia-trist was also asked (

3

) whether they were aware that the use was off-label (

4

) whether the patient had been informed the use was off-label and if not the reasons for this and (

5

) details of professionals con-sulted and case note documentation Patientsrsquo demo-graphic and legal details were obtained from the medical records department

Results

A total of

56

patients were studied of which

38

(

68

) were receiving a psychotropic drug Twenty-six (

46

) patients were prescribed one or more psychotropic drugs for an unlicensed indication (

6

of these were receiving two psychotropics for unlicensed indica-

tions) No patients were receiving psychotropic med-ication at above BNF recommended maximum dosages Of the

86

prescriptions for psychotropics

32

(

37

) were off-label

Characteristics of patients prescribed off-label mood stabilizers

The demographic legal and clinical characteristics of the

26

patients prescribed off-label psychotropics are given in Table

1

Mean age was

22

0

years (SD

7

7

) and six (

23

) were aged under

18

years All were detained

10

(

38

) under Part III of the Mental Health Act

1983

Twenty-four (

92

) had mild or moderate ID and

25

(

96

) had comorbid personality disorder andor mental illness Half (

50

) had three or more ICD-

10

psychiatric diagnoses The most common comorbid diagnoses were pervasive devel-opmental disorder F

84

(

n

=

11

42

) and schizo-phreniaschizo-affective disorder F

20

-

25

(

n

=

8

Table 1

Demographic legal and clinical characteristics of patients prescribed off-label psychotropics (

n

=

26

)

Patients (

n

=

26)

Patient characteristic

n

GenderMale 19 73Female 7 27

Age (years) Mean 220 (SD 77)Legal status

Detained 26 100ICD-10 clinical psychiatric diagnosis (es)

F20-29 Schizophrenia amp schizo-affective disorder 8 31F31 Bipolar affective disorder 6 23F40-48 Neurotic and stress-related disorders 5 19F60-61 Personality disorder 6 23F70-71 Mild or moderate mental retardation 24 92F84 Pervasive developmental disorder 11 42F90 Hyperkinetic disorder 7 27F91-92 Conduct disorder

Other diagnoses5 193 12

Number of ICD-10 clinical psychiatric diagnoses1 1 42 12 463 or more 13 50

Receiving regular antipsychotic medication 25 96Receiving mood stabiliser 12 46

ICD-

10

International Classification of Diseases ndash Tenth Revision

Some patients had more than one psychiatric diagnosis

Journal of Intellectual Disability Research

volume 49 part 11 november 2005

C Haw amp J Stubbs bull

A survey of off-label prescribing for inpatients861

copy

2005

Blackwell Publishing Ltd

Journal of Intellectual Disability Research

49

858

ndash

864

31

) Most (

n

=

25 96) were receiving regular antipsychotic medication

Nature of the off-label psychotropics

In 17 cases the off-label psychotropic was an antipsy-chotic (in 16 instances this was an atypical antipsy-chotic ndash olanzapine risperidone or aripiprazole) and in 13 cases a mood stabilizer (sodium valproate car-bamazepine or lithium) (see Table 2) In the remain-ing two cases the drugs involved were propranolol and atropine eye drops

Clinical indications for prescribing off-label psychotropics

The clinical indications for each off-label psychotro-pic are given in Table 2 The most common indica-tion was the reduction of aggression arousal and behavioural disturbance associated with pervasive developmental disorder andor ID andor personality or conduct disorder (14 instances in 13 cases using an atypical and in one case a typical antipsychotic) In two instances an atypical antipsychotic was used to reduce arousal in post-traumatic stress disorder Off-label mood stabilizers were also used to treat bipolar disorder (five instances) affective disturbance in schizophrenia or schizo-affective disorder (five instances) and other psychiatric disorders (three instances) In one case propranolol was used to treat aggression associated with conduct disorder and ID

and in another instance atropine eye drops were pre-scribed for clozapine-induced hypersalivation In the remaining case the use of an atypical antipsychotic (aripiprazole) for the treatment of schizophrenia was off-label as the patient was aged under 18 years Of the 32 prescriptions for off-label psychotropics all but two (6) were being prescribed for maintenance therapy rather than as a therapeutic trial For 17 of the 32 instances (53) of off-label usage the psychi-atrist was able to quote specific randomized con-trolled trials (RCTs) Cochrane reviews or consensus statements by expert panels to support the off-label prescription In the remaining instances the level of evidence quoted was more vague for example RCTs in adults expert opinion or case reports without quoting specific reference sources

Patient knowledge and understanding of their medication and off-label drug usage

For 29 out of the 32 (91) off-label prescriptions the psychiatrist was aware the prescription was off-label In all but two of the 32 instances the psychiatrist said that they had explained to the patient why they were receiving the prescription(s) although the psychia-trist believed that only 21 of 32 (66) patients had the capacity to understand about their medication In only 2 (6) instances had the patients been told the drug was being used off-label The reasons cited for not telling the patient the drug was being used off-label were that the patient lacked the capacity to

Table 2 Unlicensed indications for psychotropic medication in the study population (n = 32)

Psychotropic drug Unlicensed indications (no of prescriptions)

Atypical antipsychotics (risperidoneolanzapine aripiprazole)

bull Reduction of aggression arousal and behavioural disturbance associated with pervasivedevelopmental disorder andor personality disorder (or conduct disorder) andorintellectual disability (n = 13)

bull Reduction of arousal associated with post-traumatic stress disorder (n = 2)bull Schizophrenia (patient aged lt18 years) (n = 1)

Typical antipsychotics (zuclopenthixol) bull Aggression and behavioural disturbance associated with pervasive developmental disorder (n = 1)

Mood stabilisers (sodium valproatecarbamazepine lithium)

bull Bipolar affective disorder (n = 5)bull Schizophrenia or schizo-affective disorder (n = 5)bull Mood stabiliser for other psychiatric disorder (n = 3)

Propranolol bull Reduction of aggression associated with conduct disorder and intellectual disability (n = 1)

Atropine eye drops bull Clozapine-induced hypersalivation (n = 1)

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients862

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

understand the off-label concept (24 75) it might adversely affect compliance (14 44) it would dis-tress the patient (13 41) it was irrelevant to tell them because the medication was clearly beneficial (8 25) and the medication had been started by another psychiatrist (2 6) (for some patients more than one reason was given) For only 4 (13) patients had the psychiatrist documented in the case notes that the drug was being used off-label and that the patient either consented or lacked the capacity to understand the off-label concept

Consultation about the off-label drug usage with others

The psychiatrist was asked if they had consulted other mental health professionals or the patientrsquos rel-atives about the off-label usage In 26 of 32 (81) instances the psychiatrist said they had discussed the off-label usage with colleagues or obtained a second opinion A pharmacist had been consulted in 28 (88) instances the multidiscipinary team in 20 (63) and the patientrsquos relatives in 2 (6) cases

Discussion

In this survey of adolescent and adult inpatients with mild ID and mental illness 46 of patients were prescribed one or more psychotropic drugs and 37 of prescriptions for psychotropics were off-label Although in 91 of cases the consultant psychiatrist was aware that the use of the drug was off-label and had in most cases consulted other mental health pro-fessionals in only 13 of cases the off-label usage had been documented in the case notes

The strength of this study is that as far as we are aware it is the first published survey of the frequency and nature of off-label prescribing for patients with ID and mental illness We have used a structured and systematic interview to explore the off-label use of psychotropics The study limitations are that the patient population was a small and specialized one of detained inpatients at a tertiary referral centre The patients studied had both ID and mental illness and most exhibited challenging behaviour Many were offenders and some were adolescents The findings cannot therefore be generalized to community or hos-pitalized patients with ID alone Given the extent of

comorbidity and challenging behaviour a higher level of off-label prescribing might be expected in our patient population than in most samples of inpatients with ID The clinical practice of the three consultant psychiatrists responsible for the included patients was studied This is a very small sample and their practice is not necessarily representative of consultants caring for patients with ID We relied on consultantsrsquo reports of their clinical practice for example in relation to case note documentation of the off-label usageWe did not check the case notes to confirm documentation

Off-label prescribing is particularly common in children and those with ID because of the difficulties (and lack of financial incentives for drug companies) in carrying out research in these patient populations The evidence base for the use of psychotropics in children and those with ID is weak in comparison with that for mentally ill adults without ID In some instances the results of studies on adults of normal intellect can be extrapolated to adults and adoles-cents with ID for example the treatment of schizo-phrenia but for other conditions such as pervasive developmental disorder this is not possible Less evidence is available for uncommon disorders mak-ing off-label prescribing more frequent for these There is often little evidence for what constitutes an appropriate yet effective dosage for patients with ID and mental illness Effective dosages are generally much lower than for patients with mental illness alone

In this survey the commonest off-label scenario was the use of antipsychotic drugs to reduce aggres-sion arousal and behavioural disturbance in a variety of mental disorders and ID A systematic review of the effectiveness of antipsychotics for problem behav-iour in patients with ID found no definite evidence for efficacy while recognising this is an under-researched area (Brylewski amp Duggan 1999) How-ever studies in which antipsychotics have been with-drawn from these patients have reported that a significant proportion deteriorate in their behaviour (Branford 1996 Ahmed et al 2000 Stevenson et al 2004)

Given the lack of evidence for the treatment of many mental disorders and behaviours associated with ID this increases the responsibility of psychia-trists treating these conditions with off-label drugs In most instances the psychiatrists in this survey had

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients863

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

consulted other mental health professionals before prescribing but in only a very few instances (6) had the patient been told the drug was off-label This was mainly because the patient was judged to lack the capacity to understand the off-label concept We have previously found that inability to understand the off-label concept was the most commonly cited reason for not informing severely mentally ill patients of normal intellect about off-label drug usage (Haw amp Stubbs 2005) In this study case note documentation that the drug was being used off-label and whether or not the patient had been told this was the exception (13) Relatives or carers had rarely been consulted but this is likely to be because the patients had been referred from distant parts of the country and relatives therefore visited infre-quently The Draft Mental Capacity Bill (Depart-ment of Constitutional Affairs 2004) contains legislation designed to safeguard the interests of mentally incapacitated adults It proposes doctors while continuing to act in a mentally incapacitated personrsquos best interests would have a duty to consult where lsquopractical and appropriatersquo relatives carers and anyone with a lasting power of attorney in healthcare decisions This could include decisions about pharmacological treatments

Off-label usage has legal implications and brings extra responsibilities for clinicians A number of orga-nizations have issued guidance for clinicians about off-label prescribing (Royal College of Paediatrics amp Child Health 2000 Medical Protection Society 2004) and the Royal College of Psychiatrists plans to do so This guidance aims to support clinicians who may be faced with having to prescribe off-label for patients with complex needs such as those described in this study When prescribing off-label medication the clinician may find it helpful to consider the fol-lowing have medicines licensed for the indication had a proper therapeutic trial or been considered clinically inappropriate What are the risks of treat-ment What is the evidence for efficacy of the off-label drug Would a second opinion be helpful Clearly it is desirable to involve the patient as much as possible in treatment decisions including information about off-label use Where patients cannot give informed consent it may be appropriate to discuss the treat-ment with their relatives or carers In some circum-stances a trial of off-label medication may be indicated with regular monitoring of the patientrsquos

progress and withdrawal of the drug if it is ineffective or side effects are troublesome Good case note doc-umentation will support the prescriber

There is a dearth of evidence about the efficacy of psychotropic drugs for the treatment of problems and disorders associated with ID This situation is likely to continue for the foreseeable future Off-label pre-scribing for this patient group is common and requires psychiatrists to keep up to date with the available evidence base and adopt high standards in their prescribing practice

Acknowledgements

We thank the consultant psychiatrists who took part in the survey

References

Ahmed Z Fraser W Kerr M P Kiernan C Emerson E Robertson J Felce D Allen D Baxter H amp Thomas J (2000) Reducing antipsychotic medication in people with a learning disability British Journal of Psychiatry 176 42ndash6

Anonymous (1992) Prescribing unlicensed drugs or using drugs for unlicensed indications Drug and Therapeutics Bulletin 30 97ndash9

Association of the British Pharmaceutical Industry (2004) Medicines Compendium 2004 Datapharm Communica-tions Ltd Epsom UK

Branford D (1996) Factors associated with the successful or unsuccessful withdrawal of antipsychotic drug therapy prescribed for people with learning disabilities Journal of Intellectual Disability Research 40 322ndash9

British Medical Association and Royal Pharmaceutical Soci-ety of Great Britain (2004) British National Formulary No 48 British Medical Association and Royal Pharmaceutical Society of Great Britain London

Brylewski J amp Duggan L (1999) Antipsychotic medication challenging behaviour in people with learning disability a systematic review of randomised controlled trials Jour-nal of Intellectual Disability Research 43 360ndash71

Department of Constitutional Affairs (2004) Mental Capac-ity Bill The Stationary Office London

Douglas-Hall P Fuller A amp Gill-Banham S (2001) An analysis of off-licence prescribing in psychiatric medicine Pharmaceutical Journal 267 890ndash1

Haw C amp Stubbs J (2005) A survey of the off-label use of mood stabilisers in a large psychiatric hospital Journal of Psychopharmacology (in press)

Healy D amp Nutt D (1998) Prescriptions licences and evidence Psychiatric Bulletin 22 680ndash4

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients864

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

Henry V (1999) Off-label prescribing Legal implications Journal of Legal Medicine 20 365ndash83

Lowe-Ponsford F amp Baldwin D (2000) Off-label prescrib-ing by psychiatrists Psychiatric Bulletin 24 415ndash17

Medical Protection Society (2004) Prescribing issues GP Registrar 7 6

Royal College of Paediatrics and Child Health Neonatal amp Paediatric Pharmacists Group Standing Committee on Medicines (2000) The use of unlicensed medicines or licensed medicines for unlicensed applications in paedi-atric practice Retrieved December 2004 from httpwwwrcpchacukpublicationsformulary_medicineshtml

Stevenson C Rajan L Reid G Melville C McGilp R amp Cooper S A (2004) Withdrawal of antipsychotic drugs from adults with intellectual disabilities Irish Journal of Psychological Medicine 21 85ndash90

World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders Clinical descriptions and diagnostic guidelines WHO Geneva

Accepted 26 April 2005

Page 2: A survey of off-label prescribing for inpatients with mild intellectual disability and mental illness

Journal of Intellectual Disability Research

volume 49 part 11 november 2005

C Haw amp J Stubbs bull

A survey of off-label prescribing for inpatients859

copy

2005

Blackwell Publishing Ltd

Journal of Intellectual Disability Research

49

858

ndash

864

Authorisation (previously called a product licence) This includes prescribing for an unlicensed indica-tion and prescribing a dosage in excess of that spec-ified in the Marketing Authorisation and the British National Formulary (BNF) Doctors are free to pre-scribe off-label but prescribing in this way increases their professional responsibility (Henry

1999

) The use of a medicine off-label represents an area of potentially increased risk because the national body that licenses drugs for medicinal use (in the United Kingdom the Medicines and Healthcare products Regulatory Agency) has not examined the risks or benefits of using the drug in these circumstances Should the patient suffer an adverse event from the drug liability would rest with the prescriber (Anon-ymous

1992

) Some off-label usages are so common-place that they are listed in the BNF for example the use of sodium valproate for the treatment of mania in bipolar affective disorder

Quite often the licensed indications for a drug are narrow often restricted to adult patients with one particular diagnosis because it is easier in these cir-cumstances for pharmaceutical companies to carry out clinical trials demonstrating a drugrsquos efficacy It is more difficult for companies to carry out studies on special patient groups such as children and those with intellectual disabilities (ID) or those with severely disturbed mental states or relatively uncom-mon disorders For these groups it may not be pos-sible to recruit sufficient patient numbers to a clinical trial or it may be impossible to obtain informed patient consent to take part in a study Clinicians need to be aware of which prescriptions for medica-tion are off-label They need to weigh up the potential risks and benefits involved but they should not feel deterred from prescribing off-label where this is appropriate Senior clinicians and regulators from a number of European countries and North America regard off-label prescribing as a necessary part of the art of medicine (Healy amp Nutt

1998

)In psychiatry off-label prescribing is common A

postal questionnaire of psychiatrists in southern England found that

65

of respondents had pre-scribed medication off-label within the past month (Lowe-Ponsford amp Baldwin

2000

) In a survey of prescriptions for psychiatric patients in south-east England

7

5

of prescriptions were either for unli-censed indications or for doses which exceeded that stated by the product licence (Douglas-Hall

et al

2001

) We have found that among adult inpatients at a specialist psychiatric hospital

94

of prescriptions for mood stabilisers were off-label (Haw amp Stubbs

2005

)The study was carried out in a

450

-bedded chari-table hospital that provides care for patients of all ages with a wide variety of mental health problems including ID forensic and brain injury The aim of the survey was to establish the extent of off-label psychotropic prescribing for inpatients with ID and mental illness andor personality disorder Other aims were to establish the clinical indications for the off-label drugs to inquire if patients had been informed that medicines were being prescribed off-label and if not the reasons for withholding this information and to ask clinicians about their rationale for prescribing these drugs and if they had consulted others before prescribing off-label

Method

The study was approved by the Hospitalrsquos clinical audit and research committees

The charitable hospital concerned is a large ter-tiary referral centre offering specialist inpatient treatment for a wide variety of mental health prob-lems The survey was conducted in the Adult Unit and the Child and Adolescent Unit of Smyth Divi-sion of the Hospital All patients in this Division suffer with mild or borderline ID and mental illness or personality disorderconduct disorder Many are offenders who have committed a range of offences Patients are under the care of three consultant psy-chiatrists The Adult Unit comprises a medium secure admission ward and two locked wards one a rehabilitation unit The Child and Adolescent Unit comprises three locked wards for patients aged

11

ndash

23

years with ID mental illness and severely chal-lenging behaviour

For each patient JS approached their consultant psychiatrist and obtained consent to carry out a structured interview with the psychiatrist The psy-chiatrist was asked (

1

) the patientrsquos ICD-

10

clinical diagnosis (es) (World Health Organization

1992

) and (

2

) where the patient was prescribed a psycho-tropic drug the indications for its use JS then con-sulted the licensed indications given in the British National Formulary no

48

(BNF British Medical

Journal of Intellectual Disability Research

volume 49 part 11 november 2005

C Haw amp J Stubbs bull

A survey of off-label prescribing for inpatients860

copy

2005

Blackwell Publishing Ltd

Journal of Intellectual Disability Research

49

858

ndash

864

Association and Royal Pharmaceutical Society of Great Britain

2004

) and Medicines Compendium

2004

(Association of the British Pharmaceutical Industry

2004

) to determine whether or not the drug was being used off-label Where it was the psychia-trist was also asked (

3

) whether they were aware that the use was off-label (

4

) whether the patient had been informed the use was off-label and if not the reasons for this and (

5

) details of professionals con-sulted and case note documentation Patientsrsquo demo-graphic and legal details were obtained from the medical records department

Results

A total of

56

patients were studied of which

38

(

68

) were receiving a psychotropic drug Twenty-six (

46

) patients were prescribed one or more psychotropic drugs for an unlicensed indication (

6

of these were receiving two psychotropics for unlicensed indica-

tions) No patients were receiving psychotropic med-ication at above BNF recommended maximum dosages Of the

86

prescriptions for psychotropics

32

(

37

) were off-label

Characteristics of patients prescribed off-label mood stabilizers

The demographic legal and clinical characteristics of the

26

patients prescribed off-label psychotropics are given in Table

1

Mean age was

22

0

years (SD

7

7

) and six (

23

) were aged under

18

years All were detained

10

(

38

) under Part III of the Mental Health Act

1983

Twenty-four (

92

) had mild or moderate ID and

25

(

96

) had comorbid personality disorder andor mental illness Half (

50

) had three or more ICD-

10

psychiatric diagnoses The most common comorbid diagnoses were pervasive devel-opmental disorder F

84

(

n

=

11

42

) and schizo-phreniaschizo-affective disorder F

20

-

25

(

n

=

8

Table 1

Demographic legal and clinical characteristics of patients prescribed off-label psychotropics (

n

=

26

)

Patients (

n

=

26)

Patient characteristic

n

GenderMale 19 73Female 7 27

Age (years) Mean 220 (SD 77)Legal status

Detained 26 100ICD-10 clinical psychiatric diagnosis (es)

F20-29 Schizophrenia amp schizo-affective disorder 8 31F31 Bipolar affective disorder 6 23F40-48 Neurotic and stress-related disorders 5 19F60-61 Personality disorder 6 23F70-71 Mild or moderate mental retardation 24 92F84 Pervasive developmental disorder 11 42F90 Hyperkinetic disorder 7 27F91-92 Conduct disorder

Other diagnoses5 193 12

Number of ICD-10 clinical psychiatric diagnoses1 1 42 12 463 or more 13 50

Receiving regular antipsychotic medication 25 96Receiving mood stabiliser 12 46

ICD-

10

International Classification of Diseases ndash Tenth Revision

Some patients had more than one psychiatric diagnosis

Journal of Intellectual Disability Research

volume 49 part 11 november 2005

C Haw amp J Stubbs bull

A survey of off-label prescribing for inpatients861

copy

2005

Blackwell Publishing Ltd

Journal of Intellectual Disability Research

49

858

ndash

864

31

) Most (

n

=

25 96) were receiving regular antipsychotic medication

Nature of the off-label psychotropics

In 17 cases the off-label psychotropic was an antipsy-chotic (in 16 instances this was an atypical antipsy-chotic ndash olanzapine risperidone or aripiprazole) and in 13 cases a mood stabilizer (sodium valproate car-bamazepine or lithium) (see Table 2) In the remain-ing two cases the drugs involved were propranolol and atropine eye drops

Clinical indications for prescribing off-label psychotropics

The clinical indications for each off-label psychotro-pic are given in Table 2 The most common indica-tion was the reduction of aggression arousal and behavioural disturbance associated with pervasive developmental disorder andor ID andor personality or conduct disorder (14 instances in 13 cases using an atypical and in one case a typical antipsychotic) In two instances an atypical antipsychotic was used to reduce arousal in post-traumatic stress disorder Off-label mood stabilizers were also used to treat bipolar disorder (five instances) affective disturbance in schizophrenia or schizo-affective disorder (five instances) and other psychiatric disorders (three instances) In one case propranolol was used to treat aggression associated with conduct disorder and ID

and in another instance atropine eye drops were pre-scribed for clozapine-induced hypersalivation In the remaining case the use of an atypical antipsychotic (aripiprazole) for the treatment of schizophrenia was off-label as the patient was aged under 18 years Of the 32 prescriptions for off-label psychotropics all but two (6) were being prescribed for maintenance therapy rather than as a therapeutic trial For 17 of the 32 instances (53) of off-label usage the psychi-atrist was able to quote specific randomized con-trolled trials (RCTs) Cochrane reviews or consensus statements by expert panels to support the off-label prescription In the remaining instances the level of evidence quoted was more vague for example RCTs in adults expert opinion or case reports without quoting specific reference sources

Patient knowledge and understanding of their medication and off-label drug usage

For 29 out of the 32 (91) off-label prescriptions the psychiatrist was aware the prescription was off-label In all but two of the 32 instances the psychiatrist said that they had explained to the patient why they were receiving the prescription(s) although the psychia-trist believed that only 21 of 32 (66) patients had the capacity to understand about their medication In only 2 (6) instances had the patients been told the drug was being used off-label The reasons cited for not telling the patient the drug was being used off-label were that the patient lacked the capacity to

Table 2 Unlicensed indications for psychotropic medication in the study population (n = 32)

Psychotropic drug Unlicensed indications (no of prescriptions)

Atypical antipsychotics (risperidoneolanzapine aripiprazole)

bull Reduction of aggression arousal and behavioural disturbance associated with pervasivedevelopmental disorder andor personality disorder (or conduct disorder) andorintellectual disability (n = 13)

bull Reduction of arousal associated with post-traumatic stress disorder (n = 2)bull Schizophrenia (patient aged lt18 years) (n = 1)

Typical antipsychotics (zuclopenthixol) bull Aggression and behavioural disturbance associated with pervasive developmental disorder (n = 1)

Mood stabilisers (sodium valproatecarbamazepine lithium)

bull Bipolar affective disorder (n = 5)bull Schizophrenia or schizo-affective disorder (n = 5)bull Mood stabiliser for other psychiatric disorder (n = 3)

Propranolol bull Reduction of aggression associated with conduct disorder and intellectual disability (n = 1)

Atropine eye drops bull Clozapine-induced hypersalivation (n = 1)

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients862

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

understand the off-label concept (24 75) it might adversely affect compliance (14 44) it would dis-tress the patient (13 41) it was irrelevant to tell them because the medication was clearly beneficial (8 25) and the medication had been started by another psychiatrist (2 6) (for some patients more than one reason was given) For only 4 (13) patients had the psychiatrist documented in the case notes that the drug was being used off-label and that the patient either consented or lacked the capacity to understand the off-label concept

Consultation about the off-label drug usage with others

The psychiatrist was asked if they had consulted other mental health professionals or the patientrsquos rel-atives about the off-label usage In 26 of 32 (81) instances the psychiatrist said they had discussed the off-label usage with colleagues or obtained a second opinion A pharmacist had been consulted in 28 (88) instances the multidiscipinary team in 20 (63) and the patientrsquos relatives in 2 (6) cases

Discussion

In this survey of adolescent and adult inpatients with mild ID and mental illness 46 of patients were prescribed one or more psychotropic drugs and 37 of prescriptions for psychotropics were off-label Although in 91 of cases the consultant psychiatrist was aware that the use of the drug was off-label and had in most cases consulted other mental health pro-fessionals in only 13 of cases the off-label usage had been documented in the case notes

The strength of this study is that as far as we are aware it is the first published survey of the frequency and nature of off-label prescribing for patients with ID and mental illness We have used a structured and systematic interview to explore the off-label use of psychotropics The study limitations are that the patient population was a small and specialized one of detained inpatients at a tertiary referral centre The patients studied had both ID and mental illness and most exhibited challenging behaviour Many were offenders and some were adolescents The findings cannot therefore be generalized to community or hos-pitalized patients with ID alone Given the extent of

comorbidity and challenging behaviour a higher level of off-label prescribing might be expected in our patient population than in most samples of inpatients with ID The clinical practice of the three consultant psychiatrists responsible for the included patients was studied This is a very small sample and their practice is not necessarily representative of consultants caring for patients with ID We relied on consultantsrsquo reports of their clinical practice for example in relation to case note documentation of the off-label usageWe did not check the case notes to confirm documentation

Off-label prescribing is particularly common in children and those with ID because of the difficulties (and lack of financial incentives for drug companies) in carrying out research in these patient populations The evidence base for the use of psychotropics in children and those with ID is weak in comparison with that for mentally ill adults without ID In some instances the results of studies on adults of normal intellect can be extrapolated to adults and adoles-cents with ID for example the treatment of schizo-phrenia but for other conditions such as pervasive developmental disorder this is not possible Less evidence is available for uncommon disorders mak-ing off-label prescribing more frequent for these There is often little evidence for what constitutes an appropriate yet effective dosage for patients with ID and mental illness Effective dosages are generally much lower than for patients with mental illness alone

In this survey the commonest off-label scenario was the use of antipsychotic drugs to reduce aggres-sion arousal and behavioural disturbance in a variety of mental disorders and ID A systematic review of the effectiveness of antipsychotics for problem behav-iour in patients with ID found no definite evidence for efficacy while recognising this is an under-researched area (Brylewski amp Duggan 1999) How-ever studies in which antipsychotics have been with-drawn from these patients have reported that a significant proportion deteriorate in their behaviour (Branford 1996 Ahmed et al 2000 Stevenson et al 2004)

Given the lack of evidence for the treatment of many mental disorders and behaviours associated with ID this increases the responsibility of psychia-trists treating these conditions with off-label drugs In most instances the psychiatrists in this survey had

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients863

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

consulted other mental health professionals before prescribing but in only a very few instances (6) had the patient been told the drug was off-label This was mainly because the patient was judged to lack the capacity to understand the off-label concept We have previously found that inability to understand the off-label concept was the most commonly cited reason for not informing severely mentally ill patients of normal intellect about off-label drug usage (Haw amp Stubbs 2005) In this study case note documentation that the drug was being used off-label and whether or not the patient had been told this was the exception (13) Relatives or carers had rarely been consulted but this is likely to be because the patients had been referred from distant parts of the country and relatives therefore visited infre-quently The Draft Mental Capacity Bill (Depart-ment of Constitutional Affairs 2004) contains legislation designed to safeguard the interests of mentally incapacitated adults It proposes doctors while continuing to act in a mentally incapacitated personrsquos best interests would have a duty to consult where lsquopractical and appropriatersquo relatives carers and anyone with a lasting power of attorney in healthcare decisions This could include decisions about pharmacological treatments

Off-label usage has legal implications and brings extra responsibilities for clinicians A number of orga-nizations have issued guidance for clinicians about off-label prescribing (Royal College of Paediatrics amp Child Health 2000 Medical Protection Society 2004) and the Royal College of Psychiatrists plans to do so This guidance aims to support clinicians who may be faced with having to prescribe off-label for patients with complex needs such as those described in this study When prescribing off-label medication the clinician may find it helpful to consider the fol-lowing have medicines licensed for the indication had a proper therapeutic trial or been considered clinically inappropriate What are the risks of treat-ment What is the evidence for efficacy of the off-label drug Would a second opinion be helpful Clearly it is desirable to involve the patient as much as possible in treatment decisions including information about off-label use Where patients cannot give informed consent it may be appropriate to discuss the treat-ment with their relatives or carers In some circum-stances a trial of off-label medication may be indicated with regular monitoring of the patientrsquos

progress and withdrawal of the drug if it is ineffective or side effects are troublesome Good case note doc-umentation will support the prescriber

There is a dearth of evidence about the efficacy of psychotropic drugs for the treatment of problems and disorders associated with ID This situation is likely to continue for the foreseeable future Off-label pre-scribing for this patient group is common and requires psychiatrists to keep up to date with the available evidence base and adopt high standards in their prescribing practice

Acknowledgements

We thank the consultant psychiatrists who took part in the survey

References

Ahmed Z Fraser W Kerr M P Kiernan C Emerson E Robertson J Felce D Allen D Baxter H amp Thomas J (2000) Reducing antipsychotic medication in people with a learning disability British Journal of Psychiatry 176 42ndash6

Anonymous (1992) Prescribing unlicensed drugs or using drugs for unlicensed indications Drug and Therapeutics Bulletin 30 97ndash9

Association of the British Pharmaceutical Industry (2004) Medicines Compendium 2004 Datapharm Communica-tions Ltd Epsom UK

Branford D (1996) Factors associated with the successful or unsuccessful withdrawal of antipsychotic drug therapy prescribed for people with learning disabilities Journal of Intellectual Disability Research 40 322ndash9

British Medical Association and Royal Pharmaceutical Soci-ety of Great Britain (2004) British National Formulary No 48 British Medical Association and Royal Pharmaceutical Society of Great Britain London

Brylewski J amp Duggan L (1999) Antipsychotic medication challenging behaviour in people with learning disability a systematic review of randomised controlled trials Jour-nal of Intellectual Disability Research 43 360ndash71

Department of Constitutional Affairs (2004) Mental Capac-ity Bill The Stationary Office London

Douglas-Hall P Fuller A amp Gill-Banham S (2001) An analysis of off-licence prescribing in psychiatric medicine Pharmaceutical Journal 267 890ndash1

Haw C amp Stubbs J (2005) A survey of the off-label use of mood stabilisers in a large psychiatric hospital Journal of Psychopharmacology (in press)

Healy D amp Nutt D (1998) Prescriptions licences and evidence Psychiatric Bulletin 22 680ndash4

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients864

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

Henry V (1999) Off-label prescribing Legal implications Journal of Legal Medicine 20 365ndash83

Lowe-Ponsford F amp Baldwin D (2000) Off-label prescrib-ing by psychiatrists Psychiatric Bulletin 24 415ndash17

Medical Protection Society (2004) Prescribing issues GP Registrar 7 6

Royal College of Paediatrics and Child Health Neonatal amp Paediatric Pharmacists Group Standing Committee on Medicines (2000) The use of unlicensed medicines or licensed medicines for unlicensed applications in paedi-atric practice Retrieved December 2004 from httpwwwrcpchacukpublicationsformulary_medicineshtml

Stevenson C Rajan L Reid G Melville C McGilp R amp Cooper S A (2004) Withdrawal of antipsychotic drugs from adults with intellectual disabilities Irish Journal of Psychological Medicine 21 85ndash90

World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders Clinical descriptions and diagnostic guidelines WHO Geneva

Accepted 26 April 2005

Page 3: A survey of off-label prescribing for inpatients with mild intellectual disability and mental illness

Journal of Intellectual Disability Research

volume 49 part 11 november 2005

C Haw amp J Stubbs bull

A survey of off-label prescribing for inpatients860

copy

2005

Blackwell Publishing Ltd

Journal of Intellectual Disability Research

49

858

ndash

864

Association and Royal Pharmaceutical Society of Great Britain

2004

) and Medicines Compendium

2004

(Association of the British Pharmaceutical Industry

2004

) to determine whether or not the drug was being used off-label Where it was the psychia-trist was also asked (

3

) whether they were aware that the use was off-label (

4

) whether the patient had been informed the use was off-label and if not the reasons for this and (

5

) details of professionals con-sulted and case note documentation Patientsrsquo demo-graphic and legal details were obtained from the medical records department

Results

A total of

56

patients were studied of which

38

(

68

) were receiving a psychotropic drug Twenty-six (

46

) patients were prescribed one or more psychotropic drugs for an unlicensed indication (

6

of these were receiving two psychotropics for unlicensed indica-

tions) No patients were receiving psychotropic med-ication at above BNF recommended maximum dosages Of the

86

prescriptions for psychotropics

32

(

37

) were off-label

Characteristics of patients prescribed off-label mood stabilizers

The demographic legal and clinical characteristics of the

26

patients prescribed off-label psychotropics are given in Table

1

Mean age was

22

0

years (SD

7

7

) and six (

23

) were aged under

18

years All were detained

10

(

38

) under Part III of the Mental Health Act

1983

Twenty-four (

92

) had mild or moderate ID and

25

(

96

) had comorbid personality disorder andor mental illness Half (

50

) had three or more ICD-

10

psychiatric diagnoses The most common comorbid diagnoses were pervasive devel-opmental disorder F

84

(

n

=

11

42

) and schizo-phreniaschizo-affective disorder F

20

-

25

(

n

=

8

Table 1

Demographic legal and clinical characteristics of patients prescribed off-label psychotropics (

n

=

26

)

Patients (

n

=

26)

Patient characteristic

n

GenderMale 19 73Female 7 27

Age (years) Mean 220 (SD 77)Legal status

Detained 26 100ICD-10 clinical psychiatric diagnosis (es)

F20-29 Schizophrenia amp schizo-affective disorder 8 31F31 Bipolar affective disorder 6 23F40-48 Neurotic and stress-related disorders 5 19F60-61 Personality disorder 6 23F70-71 Mild or moderate mental retardation 24 92F84 Pervasive developmental disorder 11 42F90 Hyperkinetic disorder 7 27F91-92 Conduct disorder

Other diagnoses5 193 12

Number of ICD-10 clinical psychiatric diagnoses1 1 42 12 463 or more 13 50

Receiving regular antipsychotic medication 25 96Receiving mood stabiliser 12 46

ICD-

10

International Classification of Diseases ndash Tenth Revision

Some patients had more than one psychiatric diagnosis

Journal of Intellectual Disability Research

volume 49 part 11 november 2005

C Haw amp J Stubbs bull

A survey of off-label prescribing for inpatients861

copy

2005

Blackwell Publishing Ltd

Journal of Intellectual Disability Research

49

858

ndash

864

31

) Most (

n

=

25 96) were receiving regular antipsychotic medication

Nature of the off-label psychotropics

In 17 cases the off-label psychotropic was an antipsy-chotic (in 16 instances this was an atypical antipsy-chotic ndash olanzapine risperidone or aripiprazole) and in 13 cases a mood stabilizer (sodium valproate car-bamazepine or lithium) (see Table 2) In the remain-ing two cases the drugs involved were propranolol and atropine eye drops

Clinical indications for prescribing off-label psychotropics

The clinical indications for each off-label psychotro-pic are given in Table 2 The most common indica-tion was the reduction of aggression arousal and behavioural disturbance associated with pervasive developmental disorder andor ID andor personality or conduct disorder (14 instances in 13 cases using an atypical and in one case a typical antipsychotic) In two instances an atypical antipsychotic was used to reduce arousal in post-traumatic stress disorder Off-label mood stabilizers were also used to treat bipolar disorder (five instances) affective disturbance in schizophrenia or schizo-affective disorder (five instances) and other psychiatric disorders (three instances) In one case propranolol was used to treat aggression associated with conduct disorder and ID

and in another instance atropine eye drops were pre-scribed for clozapine-induced hypersalivation In the remaining case the use of an atypical antipsychotic (aripiprazole) for the treatment of schizophrenia was off-label as the patient was aged under 18 years Of the 32 prescriptions for off-label psychotropics all but two (6) were being prescribed for maintenance therapy rather than as a therapeutic trial For 17 of the 32 instances (53) of off-label usage the psychi-atrist was able to quote specific randomized con-trolled trials (RCTs) Cochrane reviews or consensus statements by expert panels to support the off-label prescription In the remaining instances the level of evidence quoted was more vague for example RCTs in adults expert opinion or case reports without quoting specific reference sources

Patient knowledge and understanding of their medication and off-label drug usage

For 29 out of the 32 (91) off-label prescriptions the psychiatrist was aware the prescription was off-label In all but two of the 32 instances the psychiatrist said that they had explained to the patient why they were receiving the prescription(s) although the psychia-trist believed that only 21 of 32 (66) patients had the capacity to understand about their medication In only 2 (6) instances had the patients been told the drug was being used off-label The reasons cited for not telling the patient the drug was being used off-label were that the patient lacked the capacity to

Table 2 Unlicensed indications for psychotropic medication in the study population (n = 32)

Psychotropic drug Unlicensed indications (no of prescriptions)

Atypical antipsychotics (risperidoneolanzapine aripiprazole)

bull Reduction of aggression arousal and behavioural disturbance associated with pervasivedevelopmental disorder andor personality disorder (or conduct disorder) andorintellectual disability (n = 13)

bull Reduction of arousal associated with post-traumatic stress disorder (n = 2)bull Schizophrenia (patient aged lt18 years) (n = 1)

Typical antipsychotics (zuclopenthixol) bull Aggression and behavioural disturbance associated with pervasive developmental disorder (n = 1)

Mood stabilisers (sodium valproatecarbamazepine lithium)

bull Bipolar affective disorder (n = 5)bull Schizophrenia or schizo-affective disorder (n = 5)bull Mood stabiliser for other psychiatric disorder (n = 3)

Propranolol bull Reduction of aggression associated with conduct disorder and intellectual disability (n = 1)

Atropine eye drops bull Clozapine-induced hypersalivation (n = 1)

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients862

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

understand the off-label concept (24 75) it might adversely affect compliance (14 44) it would dis-tress the patient (13 41) it was irrelevant to tell them because the medication was clearly beneficial (8 25) and the medication had been started by another psychiatrist (2 6) (for some patients more than one reason was given) For only 4 (13) patients had the psychiatrist documented in the case notes that the drug was being used off-label and that the patient either consented or lacked the capacity to understand the off-label concept

Consultation about the off-label drug usage with others

The psychiatrist was asked if they had consulted other mental health professionals or the patientrsquos rel-atives about the off-label usage In 26 of 32 (81) instances the psychiatrist said they had discussed the off-label usage with colleagues or obtained a second opinion A pharmacist had been consulted in 28 (88) instances the multidiscipinary team in 20 (63) and the patientrsquos relatives in 2 (6) cases

Discussion

In this survey of adolescent and adult inpatients with mild ID and mental illness 46 of patients were prescribed one or more psychotropic drugs and 37 of prescriptions for psychotropics were off-label Although in 91 of cases the consultant psychiatrist was aware that the use of the drug was off-label and had in most cases consulted other mental health pro-fessionals in only 13 of cases the off-label usage had been documented in the case notes

The strength of this study is that as far as we are aware it is the first published survey of the frequency and nature of off-label prescribing for patients with ID and mental illness We have used a structured and systematic interview to explore the off-label use of psychotropics The study limitations are that the patient population was a small and specialized one of detained inpatients at a tertiary referral centre The patients studied had both ID and mental illness and most exhibited challenging behaviour Many were offenders and some were adolescents The findings cannot therefore be generalized to community or hos-pitalized patients with ID alone Given the extent of

comorbidity and challenging behaviour a higher level of off-label prescribing might be expected in our patient population than in most samples of inpatients with ID The clinical practice of the three consultant psychiatrists responsible for the included patients was studied This is a very small sample and their practice is not necessarily representative of consultants caring for patients with ID We relied on consultantsrsquo reports of their clinical practice for example in relation to case note documentation of the off-label usageWe did not check the case notes to confirm documentation

Off-label prescribing is particularly common in children and those with ID because of the difficulties (and lack of financial incentives for drug companies) in carrying out research in these patient populations The evidence base for the use of psychotropics in children and those with ID is weak in comparison with that for mentally ill adults without ID In some instances the results of studies on adults of normal intellect can be extrapolated to adults and adoles-cents with ID for example the treatment of schizo-phrenia but for other conditions such as pervasive developmental disorder this is not possible Less evidence is available for uncommon disorders mak-ing off-label prescribing more frequent for these There is often little evidence for what constitutes an appropriate yet effective dosage for patients with ID and mental illness Effective dosages are generally much lower than for patients with mental illness alone

In this survey the commonest off-label scenario was the use of antipsychotic drugs to reduce aggres-sion arousal and behavioural disturbance in a variety of mental disorders and ID A systematic review of the effectiveness of antipsychotics for problem behav-iour in patients with ID found no definite evidence for efficacy while recognising this is an under-researched area (Brylewski amp Duggan 1999) How-ever studies in which antipsychotics have been with-drawn from these patients have reported that a significant proportion deteriorate in their behaviour (Branford 1996 Ahmed et al 2000 Stevenson et al 2004)

Given the lack of evidence for the treatment of many mental disorders and behaviours associated with ID this increases the responsibility of psychia-trists treating these conditions with off-label drugs In most instances the psychiatrists in this survey had

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients863

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

consulted other mental health professionals before prescribing but in only a very few instances (6) had the patient been told the drug was off-label This was mainly because the patient was judged to lack the capacity to understand the off-label concept We have previously found that inability to understand the off-label concept was the most commonly cited reason for not informing severely mentally ill patients of normal intellect about off-label drug usage (Haw amp Stubbs 2005) In this study case note documentation that the drug was being used off-label and whether or not the patient had been told this was the exception (13) Relatives or carers had rarely been consulted but this is likely to be because the patients had been referred from distant parts of the country and relatives therefore visited infre-quently The Draft Mental Capacity Bill (Depart-ment of Constitutional Affairs 2004) contains legislation designed to safeguard the interests of mentally incapacitated adults It proposes doctors while continuing to act in a mentally incapacitated personrsquos best interests would have a duty to consult where lsquopractical and appropriatersquo relatives carers and anyone with a lasting power of attorney in healthcare decisions This could include decisions about pharmacological treatments

Off-label usage has legal implications and brings extra responsibilities for clinicians A number of orga-nizations have issued guidance for clinicians about off-label prescribing (Royal College of Paediatrics amp Child Health 2000 Medical Protection Society 2004) and the Royal College of Psychiatrists plans to do so This guidance aims to support clinicians who may be faced with having to prescribe off-label for patients with complex needs such as those described in this study When prescribing off-label medication the clinician may find it helpful to consider the fol-lowing have medicines licensed for the indication had a proper therapeutic trial or been considered clinically inappropriate What are the risks of treat-ment What is the evidence for efficacy of the off-label drug Would a second opinion be helpful Clearly it is desirable to involve the patient as much as possible in treatment decisions including information about off-label use Where patients cannot give informed consent it may be appropriate to discuss the treat-ment with their relatives or carers In some circum-stances a trial of off-label medication may be indicated with regular monitoring of the patientrsquos

progress and withdrawal of the drug if it is ineffective or side effects are troublesome Good case note doc-umentation will support the prescriber

There is a dearth of evidence about the efficacy of psychotropic drugs for the treatment of problems and disorders associated with ID This situation is likely to continue for the foreseeable future Off-label pre-scribing for this patient group is common and requires psychiatrists to keep up to date with the available evidence base and adopt high standards in their prescribing practice

Acknowledgements

We thank the consultant psychiatrists who took part in the survey

References

Ahmed Z Fraser W Kerr M P Kiernan C Emerson E Robertson J Felce D Allen D Baxter H amp Thomas J (2000) Reducing antipsychotic medication in people with a learning disability British Journal of Psychiatry 176 42ndash6

Anonymous (1992) Prescribing unlicensed drugs or using drugs for unlicensed indications Drug and Therapeutics Bulletin 30 97ndash9

Association of the British Pharmaceutical Industry (2004) Medicines Compendium 2004 Datapharm Communica-tions Ltd Epsom UK

Branford D (1996) Factors associated with the successful or unsuccessful withdrawal of antipsychotic drug therapy prescribed for people with learning disabilities Journal of Intellectual Disability Research 40 322ndash9

British Medical Association and Royal Pharmaceutical Soci-ety of Great Britain (2004) British National Formulary No 48 British Medical Association and Royal Pharmaceutical Society of Great Britain London

Brylewski J amp Duggan L (1999) Antipsychotic medication challenging behaviour in people with learning disability a systematic review of randomised controlled trials Jour-nal of Intellectual Disability Research 43 360ndash71

Department of Constitutional Affairs (2004) Mental Capac-ity Bill The Stationary Office London

Douglas-Hall P Fuller A amp Gill-Banham S (2001) An analysis of off-licence prescribing in psychiatric medicine Pharmaceutical Journal 267 890ndash1

Haw C amp Stubbs J (2005) A survey of the off-label use of mood stabilisers in a large psychiatric hospital Journal of Psychopharmacology (in press)

Healy D amp Nutt D (1998) Prescriptions licences and evidence Psychiatric Bulletin 22 680ndash4

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients864

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

Henry V (1999) Off-label prescribing Legal implications Journal of Legal Medicine 20 365ndash83

Lowe-Ponsford F amp Baldwin D (2000) Off-label prescrib-ing by psychiatrists Psychiatric Bulletin 24 415ndash17

Medical Protection Society (2004) Prescribing issues GP Registrar 7 6

Royal College of Paediatrics and Child Health Neonatal amp Paediatric Pharmacists Group Standing Committee on Medicines (2000) The use of unlicensed medicines or licensed medicines for unlicensed applications in paedi-atric practice Retrieved December 2004 from httpwwwrcpchacukpublicationsformulary_medicineshtml

Stevenson C Rajan L Reid G Melville C McGilp R amp Cooper S A (2004) Withdrawal of antipsychotic drugs from adults with intellectual disabilities Irish Journal of Psychological Medicine 21 85ndash90

World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders Clinical descriptions and diagnostic guidelines WHO Geneva

Accepted 26 April 2005

Page 4: A survey of off-label prescribing for inpatients with mild intellectual disability and mental illness

Journal of Intellectual Disability Research

volume 49 part 11 november 2005

C Haw amp J Stubbs bull

A survey of off-label prescribing for inpatients861

copy

2005

Blackwell Publishing Ltd

Journal of Intellectual Disability Research

49

858

ndash

864

31

) Most (

n

=

25 96) were receiving regular antipsychotic medication

Nature of the off-label psychotropics

In 17 cases the off-label psychotropic was an antipsy-chotic (in 16 instances this was an atypical antipsy-chotic ndash olanzapine risperidone or aripiprazole) and in 13 cases a mood stabilizer (sodium valproate car-bamazepine or lithium) (see Table 2) In the remain-ing two cases the drugs involved were propranolol and atropine eye drops

Clinical indications for prescribing off-label psychotropics

The clinical indications for each off-label psychotro-pic are given in Table 2 The most common indica-tion was the reduction of aggression arousal and behavioural disturbance associated with pervasive developmental disorder andor ID andor personality or conduct disorder (14 instances in 13 cases using an atypical and in one case a typical antipsychotic) In two instances an atypical antipsychotic was used to reduce arousal in post-traumatic stress disorder Off-label mood stabilizers were also used to treat bipolar disorder (five instances) affective disturbance in schizophrenia or schizo-affective disorder (five instances) and other psychiatric disorders (three instances) In one case propranolol was used to treat aggression associated with conduct disorder and ID

and in another instance atropine eye drops were pre-scribed for clozapine-induced hypersalivation In the remaining case the use of an atypical antipsychotic (aripiprazole) for the treatment of schizophrenia was off-label as the patient was aged under 18 years Of the 32 prescriptions for off-label psychotropics all but two (6) were being prescribed for maintenance therapy rather than as a therapeutic trial For 17 of the 32 instances (53) of off-label usage the psychi-atrist was able to quote specific randomized con-trolled trials (RCTs) Cochrane reviews or consensus statements by expert panels to support the off-label prescription In the remaining instances the level of evidence quoted was more vague for example RCTs in adults expert opinion or case reports without quoting specific reference sources

Patient knowledge and understanding of their medication and off-label drug usage

For 29 out of the 32 (91) off-label prescriptions the psychiatrist was aware the prescription was off-label In all but two of the 32 instances the psychiatrist said that they had explained to the patient why they were receiving the prescription(s) although the psychia-trist believed that only 21 of 32 (66) patients had the capacity to understand about their medication In only 2 (6) instances had the patients been told the drug was being used off-label The reasons cited for not telling the patient the drug was being used off-label were that the patient lacked the capacity to

Table 2 Unlicensed indications for psychotropic medication in the study population (n = 32)

Psychotropic drug Unlicensed indications (no of prescriptions)

Atypical antipsychotics (risperidoneolanzapine aripiprazole)

bull Reduction of aggression arousal and behavioural disturbance associated with pervasivedevelopmental disorder andor personality disorder (or conduct disorder) andorintellectual disability (n = 13)

bull Reduction of arousal associated with post-traumatic stress disorder (n = 2)bull Schizophrenia (patient aged lt18 years) (n = 1)

Typical antipsychotics (zuclopenthixol) bull Aggression and behavioural disturbance associated with pervasive developmental disorder (n = 1)

Mood stabilisers (sodium valproatecarbamazepine lithium)

bull Bipolar affective disorder (n = 5)bull Schizophrenia or schizo-affective disorder (n = 5)bull Mood stabiliser for other psychiatric disorder (n = 3)

Propranolol bull Reduction of aggression associated with conduct disorder and intellectual disability (n = 1)

Atropine eye drops bull Clozapine-induced hypersalivation (n = 1)

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients862

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

understand the off-label concept (24 75) it might adversely affect compliance (14 44) it would dis-tress the patient (13 41) it was irrelevant to tell them because the medication was clearly beneficial (8 25) and the medication had been started by another psychiatrist (2 6) (for some patients more than one reason was given) For only 4 (13) patients had the psychiatrist documented in the case notes that the drug was being used off-label and that the patient either consented or lacked the capacity to understand the off-label concept

Consultation about the off-label drug usage with others

The psychiatrist was asked if they had consulted other mental health professionals or the patientrsquos rel-atives about the off-label usage In 26 of 32 (81) instances the psychiatrist said they had discussed the off-label usage with colleagues or obtained a second opinion A pharmacist had been consulted in 28 (88) instances the multidiscipinary team in 20 (63) and the patientrsquos relatives in 2 (6) cases

Discussion

In this survey of adolescent and adult inpatients with mild ID and mental illness 46 of patients were prescribed one or more psychotropic drugs and 37 of prescriptions for psychotropics were off-label Although in 91 of cases the consultant psychiatrist was aware that the use of the drug was off-label and had in most cases consulted other mental health pro-fessionals in only 13 of cases the off-label usage had been documented in the case notes

The strength of this study is that as far as we are aware it is the first published survey of the frequency and nature of off-label prescribing for patients with ID and mental illness We have used a structured and systematic interview to explore the off-label use of psychotropics The study limitations are that the patient population was a small and specialized one of detained inpatients at a tertiary referral centre The patients studied had both ID and mental illness and most exhibited challenging behaviour Many were offenders and some were adolescents The findings cannot therefore be generalized to community or hos-pitalized patients with ID alone Given the extent of

comorbidity and challenging behaviour a higher level of off-label prescribing might be expected in our patient population than in most samples of inpatients with ID The clinical practice of the three consultant psychiatrists responsible for the included patients was studied This is a very small sample and their practice is not necessarily representative of consultants caring for patients with ID We relied on consultantsrsquo reports of their clinical practice for example in relation to case note documentation of the off-label usageWe did not check the case notes to confirm documentation

Off-label prescribing is particularly common in children and those with ID because of the difficulties (and lack of financial incentives for drug companies) in carrying out research in these patient populations The evidence base for the use of psychotropics in children and those with ID is weak in comparison with that for mentally ill adults without ID In some instances the results of studies on adults of normal intellect can be extrapolated to adults and adoles-cents with ID for example the treatment of schizo-phrenia but for other conditions such as pervasive developmental disorder this is not possible Less evidence is available for uncommon disorders mak-ing off-label prescribing more frequent for these There is often little evidence for what constitutes an appropriate yet effective dosage for patients with ID and mental illness Effective dosages are generally much lower than for patients with mental illness alone

In this survey the commonest off-label scenario was the use of antipsychotic drugs to reduce aggres-sion arousal and behavioural disturbance in a variety of mental disorders and ID A systematic review of the effectiveness of antipsychotics for problem behav-iour in patients with ID found no definite evidence for efficacy while recognising this is an under-researched area (Brylewski amp Duggan 1999) How-ever studies in which antipsychotics have been with-drawn from these patients have reported that a significant proportion deteriorate in their behaviour (Branford 1996 Ahmed et al 2000 Stevenson et al 2004)

Given the lack of evidence for the treatment of many mental disorders and behaviours associated with ID this increases the responsibility of psychia-trists treating these conditions with off-label drugs In most instances the psychiatrists in this survey had

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients863

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

consulted other mental health professionals before prescribing but in only a very few instances (6) had the patient been told the drug was off-label This was mainly because the patient was judged to lack the capacity to understand the off-label concept We have previously found that inability to understand the off-label concept was the most commonly cited reason for not informing severely mentally ill patients of normal intellect about off-label drug usage (Haw amp Stubbs 2005) In this study case note documentation that the drug was being used off-label and whether or not the patient had been told this was the exception (13) Relatives or carers had rarely been consulted but this is likely to be because the patients had been referred from distant parts of the country and relatives therefore visited infre-quently The Draft Mental Capacity Bill (Depart-ment of Constitutional Affairs 2004) contains legislation designed to safeguard the interests of mentally incapacitated adults It proposes doctors while continuing to act in a mentally incapacitated personrsquos best interests would have a duty to consult where lsquopractical and appropriatersquo relatives carers and anyone with a lasting power of attorney in healthcare decisions This could include decisions about pharmacological treatments

Off-label usage has legal implications and brings extra responsibilities for clinicians A number of orga-nizations have issued guidance for clinicians about off-label prescribing (Royal College of Paediatrics amp Child Health 2000 Medical Protection Society 2004) and the Royal College of Psychiatrists plans to do so This guidance aims to support clinicians who may be faced with having to prescribe off-label for patients with complex needs such as those described in this study When prescribing off-label medication the clinician may find it helpful to consider the fol-lowing have medicines licensed for the indication had a proper therapeutic trial or been considered clinically inappropriate What are the risks of treat-ment What is the evidence for efficacy of the off-label drug Would a second opinion be helpful Clearly it is desirable to involve the patient as much as possible in treatment decisions including information about off-label use Where patients cannot give informed consent it may be appropriate to discuss the treat-ment with their relatives or carers In some circum-stances a trial of off-label medication may be indicated with regular monitoring of the patientrsquos

progress and withdrawal of the drug if it is ineffective or side effects are troublesome Good case note doc-umentation will support the prescriber

There is a dearth of evidence about the efficacy of psychotropic drugs for the treatment of problems and disorders associated with ID This situation is likely to continue for the foreseeable future Off-label pre-scribing for this patient group is common and requires psychiatrists to keep up to date with the available evidence base and adopt high standards in their prescribing practice

Acknowledgements

We thank the consultant psychiatrists who took part in the survey

References

Ahmed Z Fraser W Kerr M P Kiernan C Emerson E Robertson J Felce D Allen D Baxter H amp Thomas J (2000) Reducing antipsychotic medication in people with a learning disability British Journal of Psychiatry 176 42ndash6

Anonymous (1992) Prescribing unlicensed drugs or using drugs for unlicensed indications Drug and Therapeutics Bulletin 30 97ndash9

Association of the British Pharmaceutical Industry (2004) Medicines Compendium 2004 Datapharm Communica-tions Ltd Epsom UK

Branford D (1996) Factors associated with the successful or unsuccessful withdrawal of antipsychotic drug therapy prescribed for people with learning disabilities Journal of Intellectual Disability Research 40 322ndash9

British Medical Association and Royal Pharmaceutical Soci-ety of Great Britain (2004) British National Formulary No 48 British Medical Association and Royal Pharmaceutical Society of Great Britain London

Brylewski J amp Duggan L (1999) Antipsychotic medication challenging behaviour in people with learning disability a systematic review of randomised controlled trials Jour-nal of Intellectual Disability Research 43 360ndash71

Department of Constitutional Affairs (2004) Mental Capac-ity Bill The Stationary Office London

Douglas-Hall P Fuller A amp Gill-Banham S (2001) An analysis of off-licence prescribing in psychiatric medicine Pharmaceutical Journal 267 890ndash1

Haw C amp Stubbs J (2005) A survey of the off-label use of mood stabilisers in a large psychiatric hospital Journal of Psychopharmacology (in press)

Healy D amp Nutt D (1998) Prescriptions licences and evidence Psychiatric Bulletin 22 680ndash4

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients864

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

Henry V (1999) Off-label prescribing Legal implications Journal of Legal Medicine 20 365ndash83

Lowe-Ponsford F amp Baldwin D (2000) Off-label prescrib-ing by psychiatrists Psychiatric Bulletin 24 415ndash17

Medical Protection Society (2004) Prescribing issues GP Registrar 7 6

Royal College of Paediatrics and Child Health Neonatal amp Paediatric Pharmacists Group Standing Committee on Medicines (2000) The use of unlicensed medicines or licensed medicines for unlicensed applications in paedi-atric practice Retrieved December 2004 from httpwwwrcpchacukpublicationsformulary_medicineshtml

Stevenson C Rajan L Reid G Melville C McGilp R amp Cooper S A (2004) Withdrawal of antipsychotic drugs from adults with intellectual disabilities Irish Journal of Psychological Medicine 21 85ndash90

World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders Clinical descriptions and diagnostic guidelines WHO Geneva

Accepted 26 April 2005

Page 5: A survey of off-label prescribing for inpatients with mild intellectual disability and mental illness

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients862

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

understand the off-label concept (24 75) it might adversely affect compliance (14 44) it would dis-tress the patient (13 41) it was irrelevant to tell them because the medication was clearly beneficial (8 25) and the medication had been started by another psychiatrist (2 6) (for some patients more than one reason was given) For only 4 (13) patients had the psychiatrist documented in the case notes that the drug was being used off-label and that the patient either consented or lacked the capacity to understand the off-label concept

Consultation about the off-label drug usage with others

The psychiatrist was asked if they had consulted other mental health professionals or the patientrsquos rel-atives about the off-label usage In 26 of 32 (81) instances the psychiatrist said they had discussed the off-label usage with colleagues or obtained a second opinion A pharmacist had been consulted in 28 (88) instances the multidiscipinary team in 20 (63) and the patientrsquos relatives in 2 (6) cases

Discussion

In this survey of adolescent and adult inpatients with mild ID and mental illness 46 of patients were prescribed one or more psychotropic drugs and 37 of prescriptions for psychotropics were off-label Although in 91 of cases the consultant psychiatrist was aware that the use of the drug was off-label and had in most cases consulted other mental health pro-fessionals in only 13 of cases the off-label usage had been documented in the case notes

The strength of this study is that as far as we are aware it is the first published survey of the frequency and nature of off-label prescribing for patients with ID and mental illness We have used a structured and systematic interview to explore the off-label use of psychotropics The study limitations are that the patient population was a small and specialized one of detained inpatients at a tertiary referral centre The patients studied had both ID and mental illness and most exhibited challenging behaviour Many were offenders and some were adolescents The findings cannot therefore be generalized to community or hos-pitalized patients with ID alone Given the extent of

comorbidity and challenging behaviour a higher level of off-label prescribing might be expected in our patient population than in most samples of inpatients with ID The clinical practice of the three consultant psychiatrists responsible for the included patients was studied This is a very small sample and their practice is not necessarily representative of consultants caring for patients with ID We relied on consultantsrsquo reports of their clinical practice for example in relation to case note documentation of the off-label usageWe did not check the case notes to confirm documentation

Off-label prescribing is particularly common in children and those with ID because of the difficulties (and lack of financial incentives for drug companies) in carrying out research in these patient populations The evidence base for the use of psychotropics in children and those with ID is weak in comparison with that for mentally ill adults without ID In some instances the results of studies on adults of normal intellect can be extrapolated to adults and adoles-cents with ID for example the treatment of schizo-phrenia but for other conditions such as pervasive developmental disorder this is not possible Less evidence is available for uncommon disorders mak-ing off-label prescribing more frequent for these There is often little evidence for what constitutes an appropriate yet effective dosage for patients with ID and mental illness Effective dosages are generally much lower than for patients with mental illness alone

In this survey the commonest off-label scenario was the use of antipsychotic drugs to reduce aggres-sion arousal and behavioural disturbance in a variety of mental disorders and ID A systematic review of the effectiveness of antipsychotics for problem behav-iour in patients with ID found no definite evidence for efficacy while recognising this is an under-researched area (Brylewski amp Duggan 1999) How-ever studies in which antipsychotics have been with-drawn from these patients have reported that a significant proportion deteriorate in their behaviour (Branford 1996 Ahmed et al 2000 Stevenson et al 2004)

Given the lack of evidence for the treatment of many mental disorders and behaviours associated with ID this increases the responsibility of psychia-trists treating these conditions with off-label drugs In most instances the psychiatrists in this survey had

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients863

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

consulted other mental health professionals before prescribing but in only a very few instances (6) had the patient been told the drug was off-label This was mainly because the patient was judged to lack the capacity to understand the off-label concept We have previously found that inability to understand the off-label concept was the most commonly cited reason for not informing severely mentally ill patients of normal intellect about off-label drug usage (Haw amp Stubbs 2005) In this study case note documentation that the drug was being used off-label and whether or not the patient had been told this was the exception (13) Relatives or carers had rarely been consulted but this is likely to be because the patients had been referred from distant parts of the country and relatives therefore visited infre-quently The Draft Mental Capacity Bill (Depart-ment of Constitutional Affairs 2004) contains legislation designed to safeguard the interests of mentally incapacitated adults It proposes doctors while continuing to act in a mentally incapacitated personrsquos best interests would have a duty to consult where lsquopractical and appropriatersquo relatives carers and anyone with a lasting power of attorney in healthcare decisions This could include decisions about pharmacological treatments

Off-label usage has legal implications and brings extra responsibilities for clinicians A number of orga-nizations have issued guidance for clinicians about off-label prescribing (Royal College of Paediatrics amp Child Health 2000 Medical Protection Society 2004) and the Royal College of Psychiatrists plans to do so This guidance aims to support clinicians who may be faced with having to prescribe off-label for patients with complex needs such as those described in this study When prescribing off-label medication the clinician may find it helpful to consider the fol-lowing have medicines licensed for the indication had a proper therapeutic trial or been considered clinically inappropriate What are the risks of treat-ment What is the evidence for efficacy of the off-label drug Would a second opinion be helpful Clearly it is desirable to involve the patient as much as possible in treatment decisions including information about off-label use Where patients cannot give informed consent it may be appropriate to discuss the treat-ment with their relatives or carers In some circum-stances a trial of off-label medication may be indicated with regular monitoring of the patientrsquos

progress and withdrawal of the drug if it is ineffective or side effects are troublesome Good case note doc-umentation will support the prescriber

There is a dearth of evidence about the efficacy of psychotropic drugs for the treatment of problems and disorders associated with ID This situation is likely to continue for the foreseeable future Off-label pre-scribing for this patient group is common and requires psychiatrists to keep up to date with the available evidence base and adopt high standards in their prescribing practice

Acknowledgements

We thank the consultant psychiatrists who took part in the survey

References

Ahmed Z Fraser W Kerr M P Kiernan C Emerson E Robertson J Felce D Allen D Baxter H amp Thomas J (2000) Reducing antipsychotic medication in people with a learning disability British Journal of Psychiatry 176 42ndash6

Anonymous (1992) Prescribing unlicensed drugs or using drugs for unlicensed indications Drug and Therapeutics Bulletin 30 97ndash9

Association of the British Pharmaceutical Industry (2004) Medicines Compendium 2004 Datapharm Communica-tions Ltd Epsom UK

Branford D (1996) Factors associated with the successful or unsuccessful withdrawal of antipsychotic drug therapy prescribed for people with learning disabilities Journal of Intellectual Disability Research 40 322ndash9

British Medical Association and Royal Pharmaceutical Soci-ety of Great Britain (2004) British National Formulary No 48 British Medical Association and Royal Pharmaceutical Society of Great Britain London

Brylewski J amp Duggan L (1999) Antipsychotic medication challenging behaviour in people with learning disability a systematic review of randomised controlled trials Jour-nal of Intellectual Disability Research 43 360ndash71

Department of Constitutional Affairs (2004) Mental Capac-ity Bill The Stationary Office London

Douglas-Hall P Fuller A amp Gill-Banham S (2001) An analysis of off-licence prescribing in psychiatric medicine Pharmaceutical Journal 267 890ndash1

Haw C amp Stubbs J (2005) A survey of the off-label use of mood stabilisers in a large psychiatric hospital Journal of Psychopharmacology (in press)

Healy D amp Nutt D (1998) Prescriptions licences and evidence Psychiatric Bulletin 22 680ndash4

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients864

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

Henry V (1999) Off-label prescribing Legal implications Journal of Legal Medicine 20 365ndash83

Lowe-Ponsford F amp Baldwin D (2000) Off-label prescrib-ing by psychiatrists Psychiatric Bulletin 24 415ndash17

Medical Protection Society (2004) Prescribing issues GP Registrar 7 6

Royal College of Paediatrics and Child Health Neonatal amp Paediatric Pharmacists Group Standing Committee on Medicines (2000) The use of unlicensed medicines or licensed medicines for unlicensed applications in paedi-atric practice Retrieved December 2004 from httpwwwrcpchacukpublicationsformulary_medicineshtml

Stevenson C Rajan L Reid G Melville C McGilp R amp Cooper S A (2004) Withdrawal of antipsychotic drugs from adults with intellectual disabilities Irish Journal of Psychological Medicine 21 85ndash90

World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders Clinical descriptions and diagnostic guidelines WHO Geneva

Accepted 26 April 2005

Page 6: A survey of off-label prescribing for inpatients with mild intellectual disability and mental illness

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients863

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

consulted other mental health professionals before prescribing but in only a very few instances (6) had the patient been told the drug was off-label This was mainly because the patient was judged to lack the capacity to understand the off-label concept We have previously found that inability to understand the off-label concept was the most commonly cited reason for not informing severely mentally ill patients of normal intellect about off-label drug usage (Haw amp Stubbs 2005) In this study case note documentation that the drug was being used off-label and whether or not the patient had been told this was the exception (13) Relatives or carers had rarely been consulted but this is likely to be because the patients had been referred from distant parts of the country and relatives therefore visited infre-quently The Draft Mental Capacity Bill (Depart-ment of Constitutional Affairs 2004) contains legislation designed to safeguard the interests of mentally incapacitated adults It proposes doctors while continuing to act in a mentally incapacitated personrsquos best interests would have a duty to consult where lsquopractical and appropriatersquo relatives carers and anyone with a lasting power of attorney in healthcare decisions This could include decisions about pharmacological treatments

Off-label usage has legal implications and brings extra responsibilities for clinicians A number of orga-nizations have issued guidance for clinicians about off-label prescribing (Royal College of Paediatrics amp Child Health 2000 Medical Protection Society 2004) and the Royal College of Psychiatrists plans to do so This guidance aims to support clinicians who may be faced with having to prescribe off-label for patients with complex needs such as those described in this study When prescribing off-label medication the clinician may find it helpful to consider the fol-lowing have medicines licensed for the indication had a proper therapeutic trial or been considered clinically inappropriate What are the risks of treat-ment What is the evidence for efficacy of the off-label drug Would a second opinion be helpful Clearly it is desirable to involve the patient as much as possible in treatment decisions including information about off-label use Where patients cannot give informed consent it may be appropriate to discuss the treat-ment with their relatives or carers In some circum-stances a trial of off-label medication may be indicated with regular monitoring of the patientrsquos

progress and withdrawal of the drug if it is ineffective or side effects are troublesome Good case note doc-umentation will support the prescriber

There is a dearth of evidence about the efficacy of psychotropic drugs for the treatment of problems and disorders associated with ID This situation is likely to continue for the foreseeable future Off-label pre-scribing for this patient group is common and requires psychiatrists to keep up to date with the available evidence base and adopt high standards in their prescribing practice

Acknowledgements

We thank the consultant psychiatrists who took part in the survey

References

Ahmed Z Fraser W Kerr M P Kiernan C Emerson E Robertson J Felce D Allen D Baxter H amp Thomas J (2000) Reducing antipsychotic medication in people with a learning disability British Journal of Psychiatry 176 42ndash6

Anonymous (1992) Prescribing unlicensed drugs or using drugs for unlicensed indications Drug and Therapeutics Bulletin 30 97ndash9

Association of the British Pharmaceutical Industry (2004) Medicines Compendium 2004 Datapharm Communica-tions Ltd Epsom UK

Branford D (1996) Factors associated with the successful or unsuccessful withdrawal of antipsychotic drug therapy prescribed for people with learning disabilities Journal of Intellectual Disability Research 40 322ndash9

British Medical Association and Royal Pharmaceutical Soci-ety of Great Britain (2004) British National Formulary No 48 British Medical Association and Royal Pharmaceutical Society of Great Britain London

Brylewski J amp Duggan L (1999) Antipsychotic medication challenging behaviour in people with learning disability a systematic review of randomised controlled trials Jour-nal of Intellectual Disability Research 43 360ndash71

Department of Constitutional Affairs (2004) Mental Capac-ity Bill The Stationary Office London

Douglas-Hall P Fuller A amp Gill-Banham S (2001) An analysis of off-licence prescribing in psychiatric medicine Pharmaceutical Journal 267 890ndash1

Haw C amp Stubbs J (2005) A survey of the off-label use of mood stabilisers in a large psychiatric hospital Journal of Psychopharmacology (in press)

Healy D amp Nutt D (1998) Prescriptions licences and evidence Psychiatric Bulletin 22 680ndash4

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients864

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

Henry V (1999) Off-label prescribing Legal implications Journal of Legal Medicine 20 365ndash83

Lowe-Ponsford F amp Baldwin D (2000) Off-label prescrib-ing by psychiatrists Psychiatric Bulletin 24 415ndash17

Medical Protection Society (2004) Prescribing issues GP Registrar 7 6

Royal College of Paediatrics and Child Health Neonatal amp Paediatric Pharmacists Group Standing Committee on Medicines (2000) The use of unlicensed medicines or licensed medicines for unlicensed applications in paedi-atric practice Retrieved December 2004 from httpwwwrcpchacukpublicationsformulary_medicineshtml

Stevenson C Rajan L Reid G Melville C McGilp R amp Cooper S A (2004) Withdrawal of antipsychotic drugs from adults with intellectual disabilities Irish Journal of Psychological Medicine 21 85ndash90

World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders Clinical descriptions and diagnostic guidelines WHO Geneva

Accepted 26 April 2005

Page 7: A survey of off-label prescribing for inpatients with mild intellectual disability and mental illness

Journal of Intellectual Disability Research volume 49 part 11 november 2005

C Haw amp J Stubbs bull A survey of off-label prescribing for inpatients864

copy 2005 Blackwell Publishing Ltd Journal of Intellectual Disability Research 49 858ndash864

Henry V (1999) Off-label prescribing Legal implications Journal of Legal Medicine 20 365ndash83

Lowe-Ponsford F amp Baldwin D (2000) Off-label prescrib-ing by psychiatrists Psychiatric Bulletin 24 415ndash17

Medical Protection Society (2004) Prescribing issues GP Registrar 7 6

Royal College of Paediatrics and Child Health Neonatal amp Paediatric Pharmacists Group Standing Committee on Medicines (2000) The use of unlicensed medicines or licensed medicines for unlicensed applications in paedi-atric practice Retrieved December 2004 from httpwwwrcpchacukpublicationsformulary_medicineshtml

Stevenson C Rajan L Reid G Melville C McGilp R amp Cooper S A (2004) Withdrawal of antipsychotic drugs from adults with intellectual disabilities Irish Journal of Psychological Medicine 21 85ndash90

World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders Clinical descriptions and diagnostic guidelines WHO Geneva

Accepted 26 April 2005