UK issues ban on second SSRI antidepressant for children

Sun, 21 Sep 2003

The UK Observer reports (below) that although antidepressant drugs of the SSRI class have not been approved for children, last year doctors (who are unaware of the severe risks associated with SSRIs) wrote 170,000 prescriptions of antidepressants for children in the UK. The number of children prescribed antidepressants in the US has not been divulged–although in 1998, a survey commissioned by the FDA found that Prozac had been prescribed to infants 3,000 times.

On Friday, the UK Committee on Medicines announced a ban on Effexor, the second SSRI to be banned for children. Four months ago, Paxil / Seroxat was similarly banned for use in children in the UK, Canada and Ireland. In both cases previously concealed evidence from controlled clinical trials conducted by these drugs’ manufacturers (Wyeth and GlaxoSmithKline) shows that children taking SSRIs were driven to acute emotional distress, leading some of them to become suicidal and homicidal. The increased suicide risk for children testing these drugs was two to three fold compared to those given a placebo.

It appears from an independent analysis that drug manufacturers have concealed the nature of the suicidal / homicidal risk by describing children’s intense emotional distress and violent behavior as "emotional lability"— a disingenuous euphemism that should have but didn’t raise questions from regulators.

The British Medicines and Healthcare Regulatory Agency (MHRA) and the FDA have announced that data from pediatric trials of SSRIs are under renewed scrutiny. However, it is hardly reassuring that these oversight agencies have only now begun to examine adverse drug reaction data inasmuch as the trials may have been completed several years ago. Were regulatory agency officials until now fooled by the term, “emotional lability?”

Corroborating evidence of an increased suicidal risk for children prescribed SSRI antidepressants comes from an Australian study published in the British Medical Journal. Wayne D. Hall, director of the Office of Public Policy and Ethics at the U of Queensland in Australia, and colleagues reported that since the sharp increase of antidepressant use (from 1991 to 2000), suicide rates fell, primarily for elderly depressed patients. However, they found the overall suicide rate for Australian men and women over age 15 did not change. Most disturbing, they found that: "there was a large increase in suicide in young people over the same time period.” See: http://my.webmd.com/content/Article/64/72434.htm Better Treatment of Depression Aids in Suicide Prevention By Jennifer Warner WebMD Medical News Reviewed By Brunilda Nazario, MD on Thursday, May 08, 2003

MHRA and FDA officials should also have questioned the safety of SSRIs inasmuch as the agencies have received thousands of reports about patients suffering severe withdrawal symptoms when they have attempted to stop taking SSRIs–a sure sign of drug dependency.

Clearly, the regulatory system is failing to meet its public responsibility by failing to ensure that physicians and consumers are informed about potential severe, adverse drug effects. It is disturbing that in the course of the drug approval process officials at the FDA and MHRA failed to analyze the data of adverse drug effects, BEFORE these agencies gave their seal of approval to market these drugs without warnings about potential hazards.

Do American and British taxpayers have to rely on the lay media to inform us about serious health risks posed by drugs that have been approved by the FDA and MHRA?

Why did the FDA approve SSRI drug labels that conceal life-threatening risks of harm from doctors and consumers? Failure to alert doctors misled them into assuming these drugs are safe enough to prescribe for children.

It is also astonishing that neither the British nor American Psychiatric Association, nor the National Institute of Mental Health have issued warnings to the psychiatrists about the dangers posed by these drugs. It seems that these associations’ financial ties to the pharmaceutical industry pose serious conflicts of interest that undermine the health and safety of children.

One must also wonder about the judgment of FDA officials who ignored the risks and approved Prozac for children under 18. No other regulatory agency in the world has approved this drug for children inasmuch as it has generated the highest number of adverse drug reports–including reports of drug-induced suicidal behavior. Are regulators extending to pharmaceutical companies freedom to maximize profits by exposing children to unsafe drugs?

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http://www.guardian.co.uk/uk_news/story/0,3604,1045902,00.html

50,000 children taking antidepressants

· Drug withdrawn over fears it made youngsters want to kill themselves · New questions for pharmaceutical firms

Sarah Boseley, health editor
Saturday September 20, 2003
The Guardian

An antidepressant which GPs have been prescribing to thousands of children, in spite of the fact that it is not recommended for their use, can cause youngsters to want to kill themselves, the government’s regulatory agency warned yesterday.

Efexor, made by the drug company Wyeth, is being taken by at least 3,000 children in the UK, it was revealed yesterday, even though guidance to doctors states that it should not be given to under 18s. It is the second antidepressant to be specifically banned from use in children in four months.

There are around 50,000 children, some as young as six, on antidepressants in the UK, the Guardian has learned. Last year, doctors wrote 170,000 prescriptions of the drugs for children under 18, even though many experts say counselling and talking therapies work better.

Just as with Seroxat, the GlaxoSmithKline drug banned in June, studies have shown that Efexor can cause children to have suicidal thoughts or to become hostile, a word which in the context of clinical trials can mean homicidal. Experts at the Medicines and Healthcare Regulatory Agency (MHRA), which licenses drugs in the UK, are urging that children should not stop taking either drug suddenly, but should consult their doctor.

The announcement raises a number of serious and urgent questions about the conduct of the pharmaceutical industry, the use of drugs in children and the ability of the MHRA to police the drug companies and safeguard public health.

“We want to see urgent action to question how drugs are regulated and licensed and how clinical trials are carried out and reported as part of this process,” said Richard Brook, chief executive of Mind, the mental health charity.

Data which suggests the drugs could be causing children to feel murderous and suicidal has been in drug company hands for several years. The studies in these two drugs and others were carried out in the mid to late-1990s, after the Food and Drug Administration in the United States asked for efficacy and safety data be cause of the rapidly increasing number of children being prescribed antidepressants.

Glaxo is already under investigation by the UK regulators for failing to hand over data showing the suicide risks earlier. One of Wyeth’s four studies in depressed and anxious children was published in 1997. Yesterday a spokesman for the company refused to give the dates of the other unpublished trials. Everything that it was necessary for the public to know was in the public domain, he said. “I’m not going to give additional information to you.”

The MHRA, which has a duty to police the companies, only realised there were risks to children after it set up a working group to review the antidepressants this year in response to public concern over Seroxat in adults. It has now become apparent that MHRA officials normally scrutinise only a summary of the trial results that they are offered by the manufacturers, and then only when the company is seeking a licence.

Seroxat belongs to a class known as the SSRIs (selective serotonin reuptake inhibitors), of which the best known is Prozac. Efexor is closely related to that class – at the dose prescribed by GPs it works in exactly the same way. None is licensed for children. Doctors are entitled to prescribe drugs “off label” – outside the licence terms; in the case of children, because trials have not been done, they often have no choice.

“The expert group will be examining urgently what implications, if any, these new findings have for other antidepressants,” said Professor Ian Weller, the review chairman.

David Healy, an expert in psychiatric drugs and director of the North Wales department of psychological medicine, said he thought up to 100,000 children could have been on SSRIs in the last few years. “With rates of serious side effects in the region of 2-3%, you are looking at a lot of kids who may have been suicidal in one way or another, who would not have been if they hadn’t been put on these drugs.”

Code words in trials can encompass a broad range of side effects. In GlaxoSmithKline’s study by Keller and colleagues, carried out in 1995-6, 11 children suffered serious side effects, compared with two taking a placebo [dummy pill]. The 11 were said to have suffered “various psychiatric events”. Five suffered “emotional lability” – a code word which embraced not only a propensity for mood swings but also suicidal thoughts. Seven children on Seroxat were hospitalised, including two with emotional lability.

The Keller study was not published until 2001. Glaxo maintains there was “no signal” that there were dangers with the drug until two further studies were done. The combined data, re-analysed to look beyond “emotional lability” specifically at suicidal thoughts and gestures, found that the drug did not work in depression in children and that suicidal thoughts, self-harm and gestures occurred in 3.2% of patients compared to 1.5% on placebo.

In a statement to the Guardian, the MHRA tacitly acknowledged that code words like “emotional lability” were unhelpful. “By the time the totality of the data were submitted to the MHRA in May [2003], the events listed under the overall term of emotional lability had been analysed to identify the individual cases of potentially suicidal behaviour and self-harm. Any high level grouping of terms potentially decreases the sensitivity of analyses.”

“From reading the published material,” said Dr Healy, “my conclusion is that emotional lability has almost always meant suicidality of one sort or another.”

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http://news.independent.co.uk/uk/health/story.jsp?story=445176

The Independent
Fears of self-harm prompt drug curb for young
By Jeremy Laurance, Health Editor
20 September 2003

An antidepressant used by about 3,000 adolescents will no longer be prescribed to children after a study found it could cause hostility, suicidal ideas and self-harm.

Efexor was licensed eight years ago and doctors wrote two million prescriptions last year, almost all for adults. But although the drug – chemical name venlafaxine – is not licensed for under 18s, GPs can prescribe it to children they think could benefit if they take personal responsibility.

The Committee on Safety of Medicines (CSM) which set up an expert working group to look at the safety of antidepressants in April, warned doctors yesterday no longer to prescribe Efexor to children. Children already on the drug will not be taken off it immediately because of concerns of the impact that would cause.

The warning is the second to be issued by the CSM on the newer anti-depressants and is certain to increase concerns that the drugs may be unsafe. In June the committee announced that Seroxat, one of the biggest selling drugs in the world, should not be prescribed to under 18s after evidence showed it could provoke suicidal thoughts and self-harm.

The Department of Health said the new advice on Efexor was based on results from two clinical trials submitted by the manufacturers, Wyeth, two weeks ago, although the company said it was submitted “earlier this year”. The trials found cases of hostility and suicidal thoughts were twice as common among those taking Efexor compared with a placebo.

Young people on the drug were also found to be more likely to complain of abdominal pain, chest pain, anorexia and mood swings.

The Department of Health emphasised that patients should not stop taking Efexor suddenly but should consult their doctor for advice. The sudden discontinuation of an antidepressant can cause withdrawal symptoms. Professor Ian Weller, chairman of the expert group, said: “We will be examining urgently what implications, if any, these new findings have for other antidepressants. Patients who are experiencing any side-effects or are concerned about their treatment should discuss these with their doctor.”

Wyeth said it informed the Medicines and Healthcare Products Regulatory Agency, which oversees the CSM, when data on the use of Efexor in children became available. “The data was submitted earlier this year and has been included as part of the CSM’s ongoing review of antidepressants,” it said.

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