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What they don't tell you about
by Anne Montague
Most medicines have been tested on just a few thousand people and even scientific trials may not reveal dangerous side-effects. We explore how your medicines could be threatening your health and ways to protect yourself.
When Mary Baker went to her doctor with PMT he prescribed the benzodiazepine drug Valium. That was in 1973. Ten years later Mary, then 40, was addicted to the drug and battling to get off it. 'I'd never heard of tranquillisers and didn't know anything about the problems of dependence before taking them,' she says. 'It took me five years to come off and during that time my weight dropped to six stone. I became too ill to work.' Mary hasn't taken Valium since 1985, but the health problems that started during her withdrawal, and which she's convinced were caused by the drug, have continued. 'As well as chronic fatigue, neuralgia and tinnitus, I have severe memory loss - great blocks of my past have been wiped out. It's a big price to pay for treating PMT,' she says.
Of course that was over 20 years ago and things have changed. Or have they? Despite the fact that during the Seventies and Eighties hundreds of thousands of people became dependent on benzodiazepines, guidelines restricting the prescription of these drugs to a maximum of four weeks weren't issued until 1988. And serious drug side-effects may still have been missed by the system that failed to alert people to the dependency problems of Valium and other benzodiazepines.
When a new drug reaches the market it has probably been tested on only a few thousand people. And however rigorous the UK's clinical testing, if a drug has been taken by a mere three or four thousand people, rarer but potentially serious reactions that affect just one in every five thousand people or fewer - as well as interactions with other drugs won't be picked up. 'In the first few years of a medicine's life, far more is known about its efficacy than its disadvantages. Knowledge of harms and risks and how best to use it in ordinary practice requires prolonged, careful monitoring,' says clinical pharmacologist Dr Andrew Herxheimer, Emeritus Fellow at the UK Cochrane Centre in Oxford and adviser to the International Society of Drug Bulletins.
How is drugs safety monitored?
Of all hospital admissions, 3-6% are due to drug reactions, so monitoring drug side-effects is vital. In the UK doctors and pharmacists have to complete a yellow card reporting any reactions they suspect may have been caused by new drugs - and any suspected serious reactions to more established drugs. New drugs carry an upside-down black triangle for around two years, which is a signal to the doctor that they need monitoring. The Medicines Control Agency (MCA), the UK's medicines regulator, uses this information, along with independent research, post marketing studies by drug companies and information from other countries, to monitor drug safety. It was the yellow card system, for example, that picked up the link between the contraceptive pill and thrombosis.
If there are serious safety concerns the drug will be withdrawn. This was the case for three drugs in 2001: Droleptan, a tranquilliser to calm psychotic patients, was linked with problems related to heart rhythm, as was Orlaam, used to treat opioid drug addiction. Lipobay, a cholesterol-lowering drug, was linked with kidney damage.
So far so good - at least in theory. In practice, says Dr Herxheimer, the yellow card system detects fewer than 10% of adverse reactions. When a team from Southampton's Drug Safety Research Unit monitored reports on 15 new drugs last year, they found only 9% of overall side-effects were reported. Although 53% of the serious reactions were reported, that still means nearly half weren't.
Are patients getting enough information?
In 1995 Millie Kieve's daughter Karen died, aged just 30, after suffering a severe psychiatric reaction to a non-psychiatric drug, and then to the drugs used to treat the side-effects. In her search for answers - and in response to her horror at what she uncovered - Millie set up APRIL, the Adverse Psychiatric Reactions Information Link. 'Karen's consultant didn't know the hallucinatory nightmares that kicked off the illness leading to her death were a recorded side-effect of the drug he had prescribed,' says Millie. 'When I started looking I was horrified at the damage caused by many commonly prescribed drugs. It's not uncommon for drug-related symptoms to be diagnosed and treated as disease. I know medicine saves lives but a head in the sand attitude is costing lives. Patients aren't given enough information.'
Recent concerns have centred on Zyban, a new anti-smoking drug licensed in the UK in June 2000 and now taken by around half a million people. By 10 January this year there had been 6975 reports of adverse drug reactions associated with Zyban, allegedly including 57 deaths. But the MCA insists there's no cause for concern. 'The number of reports should be seen in the context of the large numbers treated with Zyban,' says a spokesman, adding, 'The suspected reactions aren't necessarily caused by the drug and may relate to other factors such as nicotine withdrawal, other illnesses or other medicines that are taken concurrently.' Still, the number of adverse reaction reports on this drug seems startlingly high when the MCA receives around 18,000 reports overall each year.
Why are side-effects not being reported?
There are many reasons for under-reporting of adverse reactions. 'Sending off a yellow card isn't in the normal course of a doctor's duty. Doctors aren't well trained in recognising side-effects, and some may not realise they only have to suspect a link to report it,' says Dr Herxheimer. Doctors may not always get the information they need to monitor and advise patients effectively. Last year's survey of black triangle drugs by the Drug and Therapeutics Bulletin found that around a quarter of the summaries of product characteristics - the information given to doctors to help them prescribe and advise patients - didn't even display the black triangle. The advice provided on avoiding unwanted effects in patients was often inconsistent, unclear and unhelpful.
How reliable are the clinical trials?
When US researchers from Tufts University School of Medicine and the New England Medical Centre examined safety reporting in 192 drug trials last year, they found drug safety problems were massively under-reported. The severity of side-effects was only adequately explained in 39% of the reports and toxicity problems in only 29%.
Last year the editors of 11 of the world's top medical journals raised the alarm, saying that drug companies' commercial interests were skewing drug trial results. In a BBC interview, Dr Richard Horton, editor of The Lancet, said 90% of the research they receive for publication contains exaggerations of drug benefits, manipulation of the facts or suppression of important evidence relating to side-effects.
It's clear that better regulation and reporting is needed, and quickly. A conference in Sweden last year brought together international specialists calling for patients to be included in reporting adverse reactions - a system that exists in the US. Campaigners believe that patient reporting can reveal drug problems more quickly and highlight issues overlooked by doctors. They also think UK patients should be made aware that they're taking a black triangle drug. The MCA is currently considering the feasibility of patient reporting.
How you can protect yourself
Question your doctor. Ask about adverse effects, tell him about any other drugs you're taking and ask about possible interactions. If you need more information, do your own research. You can find the manufacturer's information in the ABPI Medicines Compendium (available in libraries) or at www.emc.vhn.net.
Ask if the medication is a new 'black triangle' drug. If so, weigh up the risks and benefits on the basis of the facts available. If you have cancer a promising new drug may be worth the risk, if it's something less serious you may prefer a tried and tested medication.
Read the Patient Information Leaflet (PIL) and keep it for as long as you take the medication. Under European law every medicine pack should contain a PIL with clear information about how to take the drug and any potential interactions and side-effects. Unfortunately, some PILs are badly written and confusing and the UK practice of splitting drug packs means that some people won't even get a PIL. If you don't get one, or don't understand it, ask your pharmacist for advice.
Follow the instructions precisely - they're there for a good reason.
Avoid alcohol with medication as it can change the way enzymes in the liver metabolise the drug and increase the risk of side-effects as well as having an effect on the drug's efficiency.
Avoid mixing herbal remedies and prescription drugs. Herbs can affect the way drugs work in the body, and with one in five people now taking some kind of herbal medicine, it's vital to be alert to the risks. St John's wort, for example, has been linked with interactions with immunosuppressant drugs, antiepileptics, HIV medication and some oral contraceptives and it's now believed that feverfew, garlic and gingko may also interact with anti-coagulant drugs.
'We don't know how big the problem is - more research is needed,' says Professor Edvard Ernst, director of Exeter University's department of Complementary Medicine. Inform your doctor and herbalist about anything you're taking and ask about interaction. The Desktop Guide To Complementary And Alternative Medicine (Harcourt, £24.99*) for GPs and consumers gives information on known and suspected herbal/medicine interactions.
Never stop taking a medicine without consulting your doctor. If you develop any side-effects, see your GP immediately for advice Last year editors of 11 of the world's top medical journals raised the alarm, saying that drug companies' commercial interests were skewing drug trial results Of all hospital admissions, 3-6% are due to drug reactions, so monitoring side-effects is vital
'Nobody warned me and now it's too late for my children'
When Rheane O'Neill wanted to become pregnant, she asked her GP's advice about sodium valproate, the drug she took to control her epilepsy. 'He referred me to my neurologist who warned of the risks of neural tube defects, hydrocephalus and cleft palate,' she says. 'By then I'd accidentally become pregnant. It was only when Conor was born that different problems emerged. He has multiple heart defects - he had open heart surgery at 16 months and now, at four, needs further surgery. He also has developmental delays.' Rheane had no idea the drugs might be responsible until a year ago when Ciaran, her second child, was 18 months old. 'He was born with only four toes on one foot and didn't thrive - at six months he weighed only 6lb 9oz. When we moved and saw a new paediatrician he said that both boys have the classic facial features of fetal valproate syndrome - button nose, wideset eyes and a thin top lip.'
Three paediatricians and a neurologist have told Rheane they believe her children's problems are caused by valproate. 'It's too late for my children, she says, 'but I want to make sure that other women are warned.'
The MCA says that despite published surveys reporting malformations in children born to women with epilepsy, it's difficult to determine whether the epilepsy or anticonvulsants such as sodium, valproate are responsible. It adds that, on available evidence, 'a causal association of developmental delay following exposure to sodium valproate in the womb is not established'.
Untreated epilepsy during pregnancy carries serious risks, and preconception counselling is essential to make women aware of the risks of medication and to find the safest treatment - the manufacturer's leaflet for sodium valproate says it should only be taken by pregnant women 'in severe cases or those resistant to other treatment'. But some women with epilepsy are still not being warned - a 1999 British Epilepsy Association (BEA) survey of 6000 women found that a third of those with children claimed to have received no advice at all during pregnancy.
APRIL (support and information for people with psychiatric reactions to medicines), PO Box 2082, Woodford Green, Essex IG8 0GS; www.april.org.uk; email firstname.lastname@example.org. BEA helpline 0808 800 5050. Fetal Anti-Convulsant Syndrome Association 01975 571340.
Text Anne Montague; Photographs Tony Hutchings; *GH readers can buy this bok by calling the GH order line on 020 7440 2475
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