Healthy Skepticism Library item: 277

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Publication type: news

Brandt E.
Government is lax with pills
2004 Mar 23

Full text:

Doctors in the United States, Great Britain and Canada have been given a warning: be cautious about using antidepressants in children. In The Netherlands, there is silence. This is typical, says Prof. Dr. Anita Hardon.

Much greater care is needed with this sort of —potentially damaging-product. “The government should protect us better against the dangerous and addictive effects of medicines.”

After years of research Prof. Dr. Anita Hardon is sure of her facts.

“Consumers are insufficiently protected against the damaging effects of medicines by the current regulatory system,” she says strongly. The medical biologist and medical anthropologist is one of the authors of the book Medicines out of Control? Antidepressants and the conspiracy of goodwill that was published last week.

Yes, that’s right: a “conspiracy”. There is a real conspiracy around medicines, and we all take part in it, argue Hardon and her British colleague, Charles Medawar, very reasonably in their book. The government, doctors and patients conspire together with the best of intentions, and the companies take part out of commercial interests. We all want to believe so badly that medicines work, that they help us-and this is discussed in the book, mainly for antidepressants, that we don’t see the negative sides any more. That we don’t want to see what history has so often told us: drugs can be dangerous and addictive. It has been shown for the hormone preparation DES and the sleeping pill Softenon; it has been seen with sedatives such as barbiturates and benzodiazepines, and it looks like it is going to happen again with antidepressants.

Certainly with this sort of medicine, where the outcome can be the horrendous illness depression-patients desperately seek and hold onto something new. Often the media also believes that new is the same as better, and make enthusiastic announcements about new pills against depression. That is how it went with the youngest generation of antidepressants, the so-called SSRIs. Emma Brunt, [a well-known Dutch writer] wrote a jubilant book about Prozac, doctors don’t want to deprive their patients of this new wonder drug, and companies push their pills gladly onto the market, with their enormous promotion machine.

Therefore, through a so-called optimistic ‘conspiracy’ the sales figures skyrocket. Between 1996 and 2001 the number of antidepressant users in The Netherlands increased by no less than 150 percent. In 2001 that led to a cost of 104 million euros. And we still hear very little about the dark side of this massive use.

Hardon: “Again and again problems about using new medicines only came to light after they had been used for some time. Now we know that benzodiazepines are addictive. It took a long time before that was recognized.”

When “benzos”a much used sleeping pill and sedative- were introduced they were seen as a safe alternative for barbiturates, that in turn, had been presented as a safe alternative to opiates. Hardon: “We believe that this history repeats itself. It is still argued if antidepressants are addictive because there are different definitions of what the word “addictive” means.

There must be more research done on them, what is done until now is insufficient. In the meantime, more and more clues appear.

Approximately 800,000 people in The Netherlands take antidepressants. “That is one in 12 people!” says Hardon. “I believe this medicine is prescribed too easily by general practitioners and psychiatrists, and is taken much too easily by consumers. They don’t fully realize that you can really become dependent on such a drug and that it can have damaging side effects.”

The results of clinical research suggest that one in four users becomes dependent on antidepressants, while the drug producers originally described this risk as “rarely”, write Hardon and Medawar. They emphasize that patients should be listened to much more, including those who report that they feel dependent on antidepressants. “My co-author, Charles Medawar, has a website on the internet that already talked about this problem at the end of the 1990s. Many antidepressant users have responded to it. They report that they just can’t stop taking these drugs. In the meantime, Dutch general practitioners have started giving advice on how to slowly reduce their use.”

But are we talking about real addiction or a more emotional dependence, a feeling that you can’t live without the drug?

“Medawar has analyzed the stories and from that it appears that when many people stop taking their medicine they develop different physical ailments than they had before they started. Such as strange flashes, sort of electric shocks in the head, things they never had before. I am a medical biologist and I think these effects result from the drug or the dose. But that needs to be researched; the evidence still needs to be found. But to begin you have to start listening much more to the signals from users and take them very seriously.”

In The Netherlands, this at least happens a little, through the Lareb institute (national registry and evaluation center of drug side effects).

Here, doctors, and since recently, patients can report side effects that they experience while using a medicine. Hardon: “I think it’s very good that the government gives funding and responsibility to Lareb. As far as I know, there is no other EU country that has a government-funded organization that also listens to users. But this happens here on a very modest scale too; the average medicine user doesn’t even know that Lareb exists.”

Where does the Dutch system fall short?

“The government responds in too lax a manner. The government feels very involved during the first evaluation round of a medicine, that is, before it comes to market. But there needs to be a more active response to problems occurring after a medicine has been registered. Because at that stage you know much more about the drug’s risks. Generally there is a tendency to first want to see hard evidence. But that evidence isn’t really sought; and no research is set up immediately if there are indications of damaging side effects.”

Hardon says drug monitoring falls short even before a drug is approved for the market. Of course, a pharmaceutical company has to carry out various research studies on the safety and efficacy of a new drug. And if they are shown, then the drug is deemed good and registered. In The Netherlands, this is done by the College ter Beoordeling van Geneesmiddelen (CBG) [Drug Evaluation Agency]. That seems very scientific, but the research is often colored, she warns, because it is sponsored by the industry.

“The registration procedures are almost completely reliant on the information supplied by the pharmaceutical industry. That is a very serious problem,” says Hardon. “When you conduct drug research at a university, with government money, different results appear than when the industry supports the research. It is becoming more and more clear and agreed that sponsored research leads to different, more rosy conclusions.”

In addition, the research data remain mostly secret for others because of the enormous commercial interests of the companies, something Medawar and Hardon call a huge problem. “Completely undemocratic,” they say. Hardon:

“The files are meters long, and the government must decide if everything checks out. Often one is reliant on the summaries that are made by the companies. On that basis alone, a drug shouldn’t be allowed on the market.

We conclude that this system gives too little emphasis to drugs’ safety and that the system really has to change. The current system puts too much emphasis on the positive side of medicines and doesn’t pay enough attention to the risks.”

Clinical research on medicines is always set up in a strict scientific way.

Hardon: “I wouldn’t count too much on that. One of our informants was responsible for years for the monitoring of clinical research in England.

She described great problems with research in practice. In fact, in 31 percent of the research studies she analyzed there was an underreporting of the drug’s risks. She says: “I would never advise a family member to take part in a clinical research study.”

In the past few weeks there has been an uproar in Great Britain about withheld research data involving the drug Seroxat (also widely used in The Netherlands.) Already on June 25, 2003, the official number of Seroxat users that had withdrawal symptoms was adjusted. It appeared that it wasn’t an average of one in 500 users but rather just one in four. “There are also other problems with this drug,” says Hardon. “There has been insufficient warning that you should use a low dose, because a higher dose is not more effective but does have more risks and side effects. There is insufficient warning about dependence on the drug, when actually there was already evidence of that in the first research data. And there are indications that the drug causes an increased risk of suicide when used in children. A warning about that has already gone out in England. Not in The Netherlands, while it is also given to children here. If this is really true, it will set off an explosion. Then this drug is done. This sort of problem could have been signaled much earlier if researchers had access to registration files.”

Moreover, the example of Seroxat and its use in children illustrate that there are many parties participating in this “conspiracy of goodwill’.

Because it is psychiatrists and other doctors who prescribe the medicine for depressed children, sometimes under pressure from parents. They do this, of course, with the best of intentions, while antidepressants officially are not marketed for use in patients under 18 years of age. Therefore, it’s not the company’s fault, but at the same time, they do very little to send a warning message to the outside world that children should never start using these pills.

After a drug has been registered, patients and doctors report side effects experienced in daily use of the drug, some innocent, some very drastic, that researchers hadn’t foreseen. And therefore hadn’t studied. Hardon: “You should collect and keep these reports from patients in a systematic way. Not that they are the evidence for me that something is wrong, but they can give new hypotheses for good research. And the government should provide more funding to examine drug use in practice.”

Where does the government’s laxness come from when following a new drug in practice?

“I have spoken informally with colleagues working at drug evaluation agencies in Europe. They say: “We can only take action against a drug beforehand, afterwards is much more difficult. The pharmaceutical industry is very capital intensive and starts legal cases as soon as there isn’t rock hard evidence. As always there is the threat of a lawsuit, this book has that too. If you could be caught with a little mistake, you will be.”

“The results of clinical data for registration act as the evidence that the medicine is safe and effective. Therefore, it’s not simple to send out a warning about a drug. I understand the caution, but our complaint is that the system fails because of that. As users, we think we are protected, while we are not protected enough.”