Individuals of all ages should be closely monitored for suicidal and homicidal thoughts and behaviours for at least 1-month after they start taking Paxil and after they increase their dosage. They should also be closely monitored after they stop taking Paxil.
Warnings about Paxil and other antidepressants have been recently published. Here are a few examples:
THE GLOBE AND MAIL
Wednesday January 16, 2008
ANTI-DEPRESSANTS DON’T WORK AS WELL AS REPORTED, STUDY SAYS
New England Journal of Medicine reports that 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
BY ANNE MCILROY
Antidepressants are far less effective than doctors have been led to believe, a new study has found.
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. But the patients he sees at the hospital are so severely ill, he said, that taking antidepressants – even if they are less effective than the literature says – is worth the risk of side effects. Depending on the drug, those can include insomnia, mild nausea or risk of increased blood pressure.
THE BRITISH BROADCASTING CORPORATION (BBC)
Monday January 29, 2007
DRUG COMPANY ‘HID’ SUICIDE LINK
Secret e-mails reveal that the UK's biggest drug company distorted trial results of an antidepressant, covering up a link with suicide in teenagers.
Panorama reveals that GlaxoSmithKline (GSK) attempted to show that Seroxat (Paxil) worked for depressed children despite failed clinical trials.
And that GSK-employed ghostwriters influenced 'independent' academics.
GSK told Panorama: "GSK utterly rejects any suggestion that it has improperly withheld drug trial information."
GSK faces action in the US where bereaved families have joined together to sue the company.
As a result, GSK has been forced to open its confidential internal archive.
Karen Barth Menzies is a partner in one of the firms representing many of the families.
She has examined thousands of the documents which are stored, box upon box, in an apartment in Malibu, California.
She said: "Even when they have negative studies that show that this drug Seroxat is going to harm some kids they still spin that study as remarkably effective and safe for children."
GSK's biggest clinical trial of Seroxat (Paxil) on children was held in the US in the 1990s and called Study 329.
Child psychiatrist Dr. Neal Ryan of the University of Pittsburgh was paid by GSK as a co-author of Study 329.
In 2002 he also gave a talk on childhood depression at a medical conference sponsored by GSK.
He said that Seroxat (Paxil) could be a suitable treatment for children and later told Panorama reporter Shelley Jofre that it probably lowered rather than raised suicide rates.
In amongst the archive of emails in Malibu, Shelley was surprised to find that her own emails to Dr. Ryan from 2002 asking questions about the safety of Seroxat (Paxil) had been forwarded to GSK asking for advice on how to respond to her.
She also found an email from a public relations executive working for GSK which said: "Originally we had planned to do extensive media relations surrounding this study until we actually viewed the results.
"Essentially the study did not really show it was effective in treating adolescent depression, which is not something we want to publicise."
But the article was published in the Journal of the American Academy of Child and Adolescent Psychiatry which says it ranks as number one in child mental health in the world.
The editor in chief of the British Medical Journal, Fiona Godlee, said that what she calls the "blind-eye culture of medicine" should be exposed by professionals.
She has written in response to the Panorama film: "We shouldn't have to rely on investigative journalists to ask the difficult questions.
"Reputations for sale are reputations at risk. We need to make that risk so high it's not worth taking."
The Medicine and Healthcare Products Regulatory Authority (MHRA) began a criminal investigation into GSK three years ago but no action has been taken yet.
A spokesperson told Panorama that the investigation has been given substantial additional resources and remains a high priority.
Seroxat (Paxil) was banned for under 18s in 2003 after the MHRA revealed that GSK's own studies showed the drug actually trebles the risk of suicidal thoughts and behaviour in depressed children.
THE GLOBE AND MAIL
Friday December 8, 2006
ANTIDEPRESSANTS RAISE SUICIDE RISK IN YOUNG ADULTS: REPORT
BY BENEDICT CAREY
In a long-awaited analysis, health officials report that antidepressant medications appeared to significantly increase the risk of suicide attempts and related behaviours in adults under 25, while reducing such risks in older people.
The analysis, the most comprehensive and rigorous to date, found that suicidal behaviour of any kind was rare, and that people taking the medications were no more likely to kill themselves than people taking placebo pills. But adults under 25 taking the drugs were more than twice as likely than those on placebos to report a single suicide attempt, or to prepare for one, by, say, writing a suicide note.
The report, which included more than a dozen medications, was compiled by the U.S. Food and Drug Administration and posted on its website this week.
The findings are the latest chapter in a long debate that has recently focused on children and adolescents. In 2004, after doing a similar analysis, the FDA required drug makers to include on their labels prominent warnings that the drugs were associated with an increased risk of suicidal thinking and behaviours in minors.
(In 2004, Health Canada also hosted an advisory panel to seek out the views of leading medical experts on safety issues surrounding the use of certain antidepressants by children. Based on those recommendations, Health Canada required drug manufacturers to change their product information - or so-called product monographs – to include warnings about the risk of suicide.)
Kelly Posner, an assistant professor of child psychiatry at Columbia University who helped the FDA analyze the data, said the findings should be treated with caution because the drug trials studied were not designed to evaluate suicide risk. “We have better, more interpretable data than we’ve ever had before,” Dr. Posner said, “but it’s still not clear that the drugs caused the behaviour.”
Andrew Nierenberg, an associate professor of psychiatry at Harvard Medical School who has consulted with drug makers, said he did not expect the findings to have any immediate effect on practice. “You have to ask the question, ‘What’s the alternative for people who are depressed or in pain?'” Dr. Nierenberg said.
He said that he had not seen any elevated suicide risk in young adults in his practice who were on the drugs, and that the drugs more often reduced suicidal thinking in people seeking treatment. “Studies like this one can be informative and make people more sensitive to the drugs’ risks,” he said, “but the thing that’s not emphasized is that the people who are a suicide risk are excluded” from the trials the FDA analyzed.
In the report, FDA scientists looked at antidepressant drug-trial data that included nearly 100,000 participants, about half of whom took the drugs. Every major antidepressant maker provided its data to the agency, which included trials for depression, as well as other disorders such as anxiety and obsessive compulsive disorder.
Comparing side-effect reports from all adults who took the drugs with those who took placebos, the agency found no significant differences in suicidal behaviour. But when they broke down the data by age, the agency found that those under 25 were 2.3 times more likely than those on placebos to report having acted on suicidal urges. The risk was the same whether the patients were taking new drugs, like Prozac from Eli Lilly and Lexapro from Forest Pharmaceuticals, or older products, like imipramine.
The drugs appeared to reduce the risk of suicidal behaviour significantly in people 65 and over.
“It is not possible to ascertain factors that would increase the risk of suicidality such as bipolar disorder or other causes of impulsivity that were not diagnosed,” the report concluded. “The lack of a protective effect” in people under 25, it added, “is an opportunity for further research.” A panel of experts is scheduled to meet next week to advise the agency on whether to take action on the report’s findings.
THE RECORDER AND TIMES
Saturday May 13, 2006
SUICIDE WARNING ISSUED FOR YOUNG ADULT PAXIL USERS
WASHINGTON (AP-CP) - The widely prescribed antidepressant Paxil may raise the risk of suicidal behaviour in young adults, its manufacturer and the U.S. Food and Drug Administration warned Friday in a letter to doctors.
The letter from GlaxoSmithKline and the FDA was accompanied by changes to the labelling of both Paxil and Paxil CR, a controlled-release version of the drug, also called Paroxetine. The medication belongs to a class known as selective serotonin reuptake inhibitors, or SSRIs.
No updated warning for Paxil is planned for Health Canada, which in 2004 ordered tougher wording on information labels for all SSRIs prescribed to Canadians of any age, spokesman Chris Williams said Friday in Ottawa.
“Rigorous clinical monitoring for suicidal ideation or other indicators of potential suicidal behaviour is advised in patients of all ages,” the current monograph reads. “This includes monitoring for agitation-type emotional and behavioural changes.”
The U.S. warning follows a recent analysis of clinical trial data from 15,000 patients treated with either Paxil or dummy pills, which revealed a higher frequency of suicidal behaviour in young adults treated with the drug.
The FDA reported that there was 11 suicide attempts - none resulting in death - among patients given Paxil in the trials. Just one patient on placebo attempted suicide.
Given the small number, the results “should be interpreted with caution,” the FDA said. Eight of the 11 attempts were made by patients between the ages of 18 and 30. All trial patients suffered from psychiatric disorders, including major depression.
A GlaxoSmithKline spokesman did not immediately return a message seeking comment. However, in the letter to doctors, Dr. John Kraus, the company’s director of clinical development for clinical psychiatry in North America, said GlaxoSmithKline PLC continues to believe the drug’s benefits outweigh its risks.
The FDA stresses that all patients, especially young adults and those who are improving, should be carefully monitored when being treated with Paxil.
In 2004, the FDA ordered that strong warnings be put on antidepressant labels about the risk of suicidal tendencies in children put on the drugs, and began analyzing whether adults face a similar risk.
All antidepressants now carry warnings on their labels cautioning patients and doctors of the risk of suicidal behaviour.
Monday May 1, 2006
ELDERLY AT RISK USING SSRI DRUGS, STUDY FINDS
Danger in first month of antidepressant use
Suicide rate much higher in early therapy
Elderly patients who are prescribed a popular brand of antidepressants are five times more likely to commit suicide during the first month of therapy than those taking other drugs, a new study shows.
The study by the Institute for Clinical Evaluative Sciences, and independent research group, released today in the American Journal of Psychiatry, looked at 1,142 suicides among Ontario residents older than 65 over nine years.
While the majority weren't taking antidepressants, those who did were at far higher risk of committing suicide in the first month of treatment.
The antidepressants, called selective serotonin reuptake inhibitors, or SSRIs, - which include Prozac, Paxil and Zoloft - have already been the subject of strong warnings from drug companies and class-action lawsuits over their increased risk of suicide among children, adolescents and adults.
In Canada, where an estimated 1 million suffer from depression, the number of prescriptions for SSRIs has doubled in the past five years, with 17.5 million prescriptions filled last year alone.
No one has studied such a large population or looked specifically at seniors, despite the large numbers of them who are prescribed these drugs, said Dr. David Juurlink, the study's lead author.
The ICES researchers linked coroners' records with patient prescription data between 1992 and 2000 and found that one in every 3,300 seniors who started taking the drugs in the past month committed suicide.
Although the risk is small, "when you multiply it by the millions of Canadians taking these drugs, then you're talking about big numbers of people", Juurlink said.
Doctors not only should closely monitor patients taking these drugs in the first month of therapy, he said, "but we need to be more judicious in how we use these drugs. We prescribe them very liberally."
"These drugs are meant to treat depression, they're not a treatment for financial problems or job dissatisfaction or any of the other sort of unhappiness people might experience in life," he said.
"Because they are perceived as very safe, we are too free with them."
Suicide is the 11th leading cause of death in the elderly, he said.
A second Canadian study in the journal found bright, artificial light therapy is as effective as antidepressants in the treatment of winter depression.
The study, co-authored by Dr. Anthony Levitt, chief of psychiatry at Sunnybrook Health Sciences Centre, found both treatments produced an improvement in 67 percent of cases treated.