Dangerous practices: Off-label prescriptions

A study in the Archives of Internal Medicine (Radley DC, Finkelstein SN, Stafford RS. Off-label prescribing among office-based physicians. Arch Intern Med. 2006; 166(9): 1021-6) in 2006 showed that one-fifth of all drugs used in the US are off-label. This means that they are used for a purpose that is not specifically listed on the label, and for which clinical trials have not been undertaken for the purposes of getting the drug approved by the likes of the FDA. The study, even more remarkably, showed that around 70% of the off-label usage was not based on any strong scientific evidence!

This 2007 article from The Independent in the UK follows up on the story.

Dangerous practices: Off-label prescriptions
Just because a drug is tested to treat one illness doesn't prove it's safe to combat other conditions. So why do doctors still prescribe 'off-label'? Jerome Burne reports
Tuesday, 3 April 2007
When you go to the GP, you can rest assured that any drugs you are given have been tested to make sure they work and are safe. Or can you? The fact is that hidden in medical journals are many reports showing many drugs are prescribed with no scientific evidence to show they work for the problem you've got.
Last year, the eminent medic Professor Michael Baum used this fact to mount an attack on CAM (complementary and alternative medicine). He urged NHS trusts to only fund treatments that are "based on solid evidence", and won a lot of support. After all, drugs have to be rigorously tested, so why shouldn't the alternatives?
Prescribing a drug for a condition it has not been tested to treat is known as "off-label" prescribing. When a drug gets a licence, it is for a particular use - to treat asthma, lower cholesterol - and the drug company has to provide evidence that it does this better than a placebo.
The scale of the "off-label" problem was revealed in a paper published in the Archives of Internal Medicine recently. It showed that 21 per cent of the 160 most commonly prescribed drugs in the US were given to people on an off-label basis. For instance, 46 per cent of heart drugs (except those to lower cholesterol or reduce blood pressure) were prescribed off-label, while in the case of Neurontin, licensed for epilepsy and nerve pain, 98 per cent of its uses were for unrelated conditions such as bi-polar disorder and depression. In the US, the FDA is under pressure to recognise the possibility that Neurontin increases suicide risk.
Of course doctors should be allowed to use their experience and judgement to prescribe unlicensed drugs where other treatments have failed. But the study - conducted at Stanford University - showed that for nearly three-quarters of the off-label uses, there was "little or no scientific support".
Off-label prescribing has a long history. In the 1980s, people with a mildly irregular heartbeat were given Tambocor or Enkaid, which reduced the risk of sudden death in people with severe arrhythmia. An estimated 200,000 Americans with a mild version were given the drugs on the assumption that it would help them, too. However, when a proper trial was finally done it showed that it doubled or tripled their risk of death.
What also needs to be examined is the role the drug companies play. Encouraging off-label prescribing, for instance, is a cheaper way of increasing drug sales than conducting large trials for every new use.
Reports in both the British Medical Journal and The Lancet have shown that sleeping pills are neither very safe nor very effective, but they still feature regularly in the top 20 most prescribed drugs in both the UK and US. But an extensive review recently found that counselling and psychotherapy were not only more effective but also without side effects. If evidence-based medicine was really what was on offer, counselling is what insomniacs would be offered. But try getting that from your GP.
Children are particularly vulnerable to being given drugs with little or no evidence base. Recently, the journal Science reported that "between 50 and 90 per cent of drugs used on adults have never been tested or licensed for children... as a result 100 million children in the EU are often prescribed off-label or unauthorised drugs".
The risks that this brings was well illustrated by the scandal involving the 60,000 children prescribed antidepressant SSRI drugs off-label in the UK. In December 2003 the drugs watchdog - the MHRA - advised doctors that, with the single exception of Prozac, no other SSRI should be used for children because they doubled the risk of suicide.
A major study in The Lancet had shown that four other SSRIs were not only unlikely to produce any "clinically important improvement" in children with depression but, in one case, had a rate of "suicide-related events" 14 times greater than a placebo. However, questions in the House of Commons revealed that 18 months later more prescriptions for those SSRIs were being issued than for Prozac.
The tendency for people to turn to non-drug treatments for less acute conditions starts to look less like a "flight from reason" and more like a rational option. Of course, the ideal that treatments should be properly tested is an excellent one but the notion that drug-based medicine has a monopoly on testing is a myth - and myths have no place in good science.
Food Is Better Medicine Than Drugs: Your Prescription for Drug-Free Health by Jerome Burne and Patrick Holford is published by Piatkus (£16.99)
Drug testing: the facts
Drugs licensed as safe and effective kill 10,000 people a year in the UK.
Trials run by drug companies have been shown to be four times more likely to produce results favourable to the company than those funded from other sources.
One study on SSRI use in children, sponsored by a drug company, concluded that "most adverse effects were not serious". An independent review found that seven of the children on the drug had been admitted to hospital.
When it was pulled from the market in 2000, the heartburn drug Propulsid had been involved in an estimated 300 deaths and 16,000 cases of heart damage. It had also been used off-label to treat infants in intensive care even though none of 20 trials had shown that it benefited them.