Off-label prescribing in psychiatric practice

Drug treatment is an essential part of much of psychiatric practice, in patients from a wide age range, across many diagnostic groups and in a variety of settings. Despite the availability of many classes of psychotropic drug, significant numbers of patients remain troubled by distressing and disabling symptoms even after a succession of licensed pharmacological treatments. Psychiatrists may then consider the prescription of a psychotropic outside the narrow terms of its licence, as part of an overall management plan. This article reviews the nature and extent of this aspect of prescribing, outlines when it may be appropriate and makes recommendations for a suggested procedure when prescribing medication ‘off-label’.

While most authorities agree that use of drugs outside the terms of their licence is a necessary part of psychiatric practice, instances of unconventional prescribing of psychotropic drugs and worries about potentially unnecessarily restrictive policies led Professor Thomas Barnes, then Chair of the Psycho-pharmacology Special Interest Group (PSIG) of the Royal College of Psychiatrists, to convene a working group with the remit of examining this issue. Discussions within this group, and comments from the PSIG and wider membership of the College, led to publication of the Council Report Use of Licensed Medicines for Unlicensed Applications in Psychiatric Practice (Royal College of Psychiatrists, 2007). Our involvement in the working group led to the writing of this article.

What is unlicensed prescribing?

In the UK, ‘licensed’ medicines are those that have received a ‘marketing authorisation’ (previously called a product licence). Licensing arrangements are determined by the Medicines Act 1968 and currently implemented through the Medicines and Healthcare products Regulatory Agency (MHRA). For each medicine, the doses, indications, cautions, contraindications and side-effects given in the British National Formulary (BNF; British Medical Association & Royal Pharmaceutical Society of Great Britain, 2007) reflect those in the manufacturer’s data sheets or summary of product characteristics (SPC), which in turn reflect the marketing authorisation. The prescription of medicines within the terms of their licence is not a guarantee of safety or efficacy. Furthermore, absence of a licence does not necessarily imply absence of evidence for an intervention. For example, low-dose propranolol has proven efficacy in treating akathisia associated with antipsychotic drugs (Adler et al, 1986) but has no licence for that condition.

Many medicines that are prescribed to patients are not licensed for the particular indication, age of the patient or dosage, and their use in these situations has been termed ‘off-label’ or ‘unlicensed’ prescribing, or the ‘use of licensed drugs for an unlicensed indication’. The use of a psychotropic drug for an unlicensed indication does not necessarily imply a safety hazard, and there are many instances where use is uncontroversial and probably advantageous to the patient. The product licence for a drug does not necessarily represent the best use of that medicine (Healy & Nutt, 1998). It may be helpful to conceptualise a spectrum of use of licensed psychotropic drugs in unlicensed applications, with some prescribing being regarded as ‘near-label’ (for example, use of the antidepressant fluoxetine as a maintenance treatment in a patient with recurrent depression).

What is the extent of unlicensed prescribing in psychiatry?
Many doctors believe that off-label prescribing is often necessary when attempting to treat certain patients, for example those whose symptoms have proven resistant to a range of treatment approaches. The extent of unlicensed prescribing in psychiatric practice is not fully known, but survey findings and research studies suggest that it is common across psychiatric specialties in the UK and in many other countries. For example, in a postal questionnaire survey of 200 National Health Service (NHS) consultants, specialist registrars and staff-grade doctors in one area of the UK, almost two-thirds of doctors reported having prescribed medicines for unlicensed applications in the previous month. Most instances (49%) involved use of a medicine outside its licensed indications, but prescriptions of drugs at doses above those described in the BNF (19%) or outside the specified age range (12%) were also common (Lowe-Ponsford & Baldwin, 2000).

General adult psychiatry
Unlicensed use of licensed drugs is a common feature of prescribing in general psychiatry settings. A cross-sectional survey of prescription cards for 266 psychiatric in-patients in acute wards from 14 NHS trusts found that 7.5% of 1387 prescriptions were outside the terms of the product licence: 75% of these were for indications not covered by the licence, and 25% were at doses above the recommended maximum. In all, 81 patients were prescribed at least one medicine off-label, typically for an unlicensed indication (Douglas-Hall et al, 2001). Other investigations suggest that unlicensed prescribing may be rather more common: for example, an audit of antipsychotic drug prescribing over 5 years in a secondary care NHS trust found that about 40% of prescriptions were for off-label applications (Hodgson & Belgamwar, 2006). Furthermore, a cross-sectional survey of prescriptions for mood-stabilising drugs in 249 in-patients in a tertiary care unit found that 28.5% were receiving prescriptions for unlicensed indications (Haw & Stubbs, 2005a).

The extent of unlicensed prescribing in UK psychiatric out-patient practice is uncertain, but research findings suggest that it is common in other European Union countries. A prospective evaluation of prescribing involving 209 out-patients in Italy found that over half of them were given off-label prescriptions of atypical antipsychotics (Barbui et al, 2002). A similar situation was found in a prescription review of 173 patients attending pharmacies in Austria, which revealed that two-thirds of them were receiving antipsychotics for unlicensed indications (Weiss et al, 2000). Similar practice is seen in non-European countries: for example, a prospective evaluation of prescribing of atypical antipsychotic drugs given to 73 981 combat veterans in the USA found that 42.8% of prescriptions were for unlicensed indications (Rosenheck et al, 2001).

David S. Baldwin and Nick Kosky

David Baldwin is Reader in Psychiatry in the Clinical Neuroscience Division of Southampton University’s School of Medicine (University Department of Mental Health, Royal Southants Hospital, Brintons Terrace, Southampton SO14 0YG, UK. Email: dsb1@soton.ac.uk) and Honorary Consultant Psychiatrist with the Mood Disorders Service, Hampshire Partnership Trust. He was Chair of the working group of the Royal College of Psychiatrists’ Psychopharmacology Special Interest Group (PSIG) on unlicensed applications of licensed drugs in psychiatric practice. His research interests include the clinical pharmacology of anxiety and depressive disorders. He leads a tertiary referral service for patients with chronic and severe mood and anxiety disorders. Nick Kosky is Consultant Psychiatrist and Clinical Director of Dorset Primary Care Trust. He was a member of the PSIG working group. He is interested in teaching psychopharmacology to non-medical staff and delivering high-quality prescribing. He is part of a prison mental heath in-reach team.

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Adler, L., Angrist, B., Peselow, E., et al (1986) A controlled assessment of propranolol in the treatment of neuroleptic-induced akathisia. British Journal of Psychiatry, 149, 42–45.[Abstract/Free Full Text]

Beck, S., Paton, C., Euba, R., et al (2001) Atypical antipsychotics in the elderly. International Journal of Psychiatry in Clinical Practice, 5, 257–261.[CrossRef]