50,000 Children Taking Antidepressants

Sarah Boseley, Health Editor, The Guardian

· Drug withdrawn over fears it made youngsters want to kill themselves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

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 counseling 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.”