Prescribing according to diagnosis: how psychiatry is different
Authors: David Taylor
Journal: World Psychiatry (2016)

Most countries in the modern world have a formal system of medicines regulation. Medicinal drugs, or more specifically their formulation and dosage, are licensed or "labelled" for certain specific indications in which their use has been shown to be broadly safe and beneficial. Prescribers can, as a consequence, have confidence in the assumption that a drug licensed for a particular precisely defined ailment is likely to be effective in that condition. Outside this regulatory framework is a body of literature which may relate to other, unlicensed or "off-label" uses. Sometimes the extra-regulatory evidence base amounts to no more than a handful of case reports, but often there are published and successful randomized controlled trials. The licensed uses of a medicine are thus merely those for which formal approval has been sought and obtained by the manufacturer. Other beneficial uses are certainly not precluded by a drug's label. In most areas of medicine, prescribing is very closely aligned with drug labeling. This is because drugs usually have a known mode of action which can be understood in the context of what is known about the condition: penicillin is bactericidal to specific bacteria; insulin replaces what the body fails to produce; antihypertensives reduce cardiac output or vascular resistance. Off-label prescribing is therefore fairly rare in physical medicine, because prescribers invariably make a firm diagnosis and prescribe a drug precisely indicated for that condition. Psychiatry is different. The biochemical or pathological basis of most mental health conditions is, at best, poorly understood. Our knowledge of the precise actions of effective drugs is likewise incomplete. Diagnostic criteria shift and sway like in no other area of medicine and named mental health conditions appear and disappear with a disturbing frequency. Alongside these factors is the troubling awareness of the frequent overlap of symptoms across formal diagnostic entities. It seems trite to point out, for example, that people with depression sometimes hear voices, or that people with bipolar disorder may suffer from anxiety. When I first worked in psychiatry in the 1980s, I was struck by the extent to which drugs were prescribed outside their license. The most common prescription I saw was for amitriptyline combined with chlorpromazine; the latter prescribed for anxiety and insomnia. Treatment of choice for alcohol withdrawal was thioridazine, a drug previously only known to me as an antipsychotic. This was also a time when antipsychotics were prescribed to almost everyone with behavioral disturbances associated with dementia. Over the years since then, my experience and observations of prescribing decision-making have been fairly uniform. Rarely is a firm diagnosis arrived at before prescribing and, perhaps more tellingly, rarely do prescribers know the precise licensed indications for every drug they prescribe. So, antipsychotics tend to be prescribed for psychotic and manic symptoms, and antidepressants tend to be prescribed for symptoms of low mood. Lithium is prescribed for mood fluctuations. Benzodiazepines are prescribed for pretty much everything. Never, in over 25 years in psychiatry, have I observed prescribers make any noticeable attempt to match a diagnosis with the licensed indication of a drug. I, for my part, would not now think to point out to a prescriber that, say, valproate has no label for prophylaxis in bipolar disorder. These informal observations are backed-up by published data. In the US, off-label prescribing of antipsychotics amounted to 74% of all prescriptions in 1995 and 60% (nine million prescriptions) in 20081. In the UK, 63% of risperidone prescribing in primary care was for unlicensed conditions in the period from 2007 to 20112. Even in secondary care, where prescribing is often more tightly controlled by local protocols, off-label prescribing is common – in my own unit we recorded off-label prescribing rates of 11% for risperidone long-acting injection3, 23% for oral aripiprazole4 and 33% for depot paliperidone5. In each case these figures represent off-label prescribing in consecutive patients during the first few months or years after the introduction of the drug or formulation. Prescribers' willingness to prescribe outside a license is thus not solely a consequence of positive experiences of prescribing for specific off-label indications – it starts straightaway. This is not necessarily poor practice: some of the most effective medicines in a particular condition do not have a license for that condition. Fluoxetine may be the most effective selective serotonin reuptake inhibitor in generalized anxiety disorder (GAD)6, but is not labeled for this condition. Sertraline is recommended as first line treatment for GAD by the National Institute for Health and Care Excellence (NICE) in the UK, but it too has no license for this indication. Quetiapine is licensed in most countries for schizophrenia, schizoaffective disorder, mania, bipolar depression and unipolar depression, but it is also effective in other conditions such as GAD7; its range of actions is such that diagnosis becomes almost irrelevant. The example of quetiapine encapsulates the issue in question. We may call it an antipsychotic but it is much more than that, because it has multiple pharmacological actions and numerous active metabolites8. The nonsense of current nomenclature – which is closely aligned with labeling − is well recognized, and other systems have been suggested. For example, neuroscience-based nomenclature classifies drugs according to their pharmacological profile rather than their primary or initial therapeutic indication9. The classification of mental health conditions gives us a false sense of order and a crude system for prescription reimbursement. It has little or no relevance to psychotropic drug action and as a consequence an accurate diagnosis is not required for optimal prescribing. David Taylor South London and Maudsley NHS Foundation Trust, Pharmacy Department, Maudsley Hospital, Denmark Hill, London, UK