Antidepressants are far less effective than doctors have been led to believe, a new study has found.
The story from today’s Globe and Mail in Canada continues:
That’s because 88 per cent of clinical trials that showed the drugs didn’t work either weren’t published in medical journals or were presented as positive findings, says the study in the New England Journal of Medicine.
It provides the first hard data on a practice known as selective reporting, in which the good news about a drug is made public but the bad news isn’t. Ethicists say it gives doctors and patients too rosy a picture. Clinicians rely on the medical literature to learn about new drugs and to help them assess whether it is worth prescribing a medication, given the risk of side effects.
The researchers examined the studies that drug companies submitted to the Food and Drug Administration in the United States when they were seeking regulatory approval for 12 antidepressants. The drugs were all approved between 1981 and 2004, and are now widely prescribed. (Canada has its own drug approvals process, which relies on essentially the same information drug companies give the FDA.)
With the antidepressants, doctors and patients didn’t get the same full picture as the regulatory agencies. All but one of the 38 positive studies given to the FDA were published, but most of the negative ones didn’t make it into print.
A doctor reading the medical journals would think that individual antidepressants were between 11- and 69-per-cent more effective than they really are, says Erick Turner, an assistant professor of psychiatry at Oregon Health and Science University and lead author on the paper.
It is not that antidepressants don’t work, Dr. Turner says. His team’s analysis showed that they all work better than sugar pills, but that their effectiveness has been exaggerated. This might tip the scales against prescribing the drugs in borderline cases, he says.
The study says it is unclear whether the drug companies didn’t submit the negative studies to the medical journals, or whether they did and the papers were rejected.
The practice of selective publication made headlines in 2004, when the attorney-general of New York launched a lawsuit against GlaxoSmithKline, in which he accused the drug company of hiding the results of several clinical trials on the use of the antidepressant Paxil in children and adolescents. The statement of claim said the studies failed to demonstrate that the drug worked, and indicated youngsters taking it could have an increased risk of having suicidal thoughts, or attempting suicide.
As part of an out-of-court settlement, the company agreed to make its clinical trials data available on a website. Other companies have followed suit. But Dr. Turner says he doesn’t know of a single doctor who regularly uses those databases.
“We are taught that the medical literature is the Holy Grail,” he said.
Trudo Lemmens, an associate professor in the faculties of law and medicine at the University of Toronto, said there has been progress since 2004, but that selective reporting is still a problem.
“There is no firm regulatory obligation to report all the results from clinical trials,” he said.
He said Dr. Turner’s finding that some negative studies were presented as positive shows there is a need to separate those who have a direct interest in the outcomes of trials from those who design, conduct, analyze and report the results.
In one case, two different studies on the drug Paxil CR – one positive and one not – were merged to give an overall positive result, Dr. Turner says. Both studies involved sites and volunteers in Canada, he says.
“I don’t have a comment on that specifically,” Peter Schram, a spokesman for GlaxoSmithKline Inc. (Canada), said yesterday.
Pierre Blier, a professor of psychiatry at the University of Ottawa who also works at the Royal Ottawa Mental Health Centre, said it is now much harder for drug companies to sweep negative findings under the carpet. He said he teaches his students not to rely only on the literature, but also on their experience and that of their colleagues. Dr. Blier, who is paid to be on the advisory board of a number of pharmaceutical companies, said that doesn’t colour his view of their actions. He said it is disconcerting to know that negative studies were not published.
If you (or Dr Blier) want to find out more, then here is a good starting point to learn about Glaxo and the infamous Study 329 and the MHRA and its 4 year long criminal investigation of Glaxo in the UK.