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unpublished trials.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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