Children and adolescents have a doubled risk of aggression and suicide when
taking one of the five most commonly prescribed antidepressants, according to
findings of a study published in The BMJ today. (The following is taken from the email sent to APRIL by the BMJ.)
However, the true risk for all associated serious harms, such as deaths,
aggression, akathisia and suicidal thoughts and attempts, remains unknown for
children, adolescents and adults, say experts.
This is because of the poor design of clinical trials that assess these
antidepressants, and the misreporting of findings in published articles.
Selective serotonin reuptake inhibitors antidepressants (SSRIs) and
serotonin-norepinephrine reuptake inhibitors (SNRIs) are the most commonly
prescribed drugs for depression.
A team of researchers from Denmark carried out a systematic review and
meta-analysis of 68 clinical study reports of 70 trials with 18,526 patients to
examine use of antidepressants and associated serious harms.
These included deaths, suicidal thoughts and attempts as well as aggression
and akathisia, a form of restlessness that may increase suicide and violence.
They examined double blind placebo controlled trials that contained patient
narratives or individual patient listings of associated harms.
Harms associated with antidepressants are often not included in published
trial reports, explain the authors. This is why they analysed clinical study
reports, prepared by pharmaceutical companies for market authorisation, and
summary trial reports, both of which usually include more information.
In adults, they found no significant associations between antidepressants and
suicide and aggression. However, a novel finding showed there was a doubling of
risk for aggression and suicides in children and adolescents.
This study has shown limitations in trials, not only in design, but also in
reporting of clinical study reports, which may have lead to "serious
under-estimation of the harms," write the authors.
They compared the results from the clinical study reports with data from
individual patient listings or narratives of adverse effects. This revealed
misclassification of deaths and suicidal events in people taking
antidepressants.
For example, four deaths were misreported by a pharmaceutical company, in all
cases favouring the antidepressant, and more than half of the suicide attempts
and suicidal ideation, for example, were coded as "emotional lability" or
"worsening of depression."
In the Eli Lilly summary trial reports, almost all deaths were noted, but
suicidal attempts were missing in 90% of instances, and information on other
outcomes was incomplete. These were "even more unreliable than we previously
suspected," write the authors.
Clinical study reports for antidepressants duloxetine, fluoxetine,
paroxetine, sertraline and venlafaxine were obtained from regulatory agencies in
the UK and Europe. Summary trial reports for duloxetine and fluoxetine were
taken from the drug company Eli Lilly's website.
However, clinical study reports could not be obtained for all trials and all
antidepressants, and
individual listings of adverse outcomes for all patients
were available for only 32 trials.
"The true risk for serious harms is still unknown [because] the low incidence
of these rare events, and the poor design and reporting of the trials, makes it
difficult to get accurate effect estimates," they explain.
They recommend "minimal use of antidepressants in children, adolescents, and
young adults, as the serious harms seem to be greater, and as their effect seems
to be below what is clinically relevant," and suggest alternative treatments
such as exercise or psychotherapy.
They also call for the need to identify "hidden information in clinical study
reports to form a more accurate view of the benefits and harms of drugs."
In an accompanying editorial, Joanna Moncrieff from University College
London, agrees that "regulators and the public need access to more comprehensive
and reliable data", and that clinical study reports "are likely to underestimate
the extent of drug related harms."
Over half the clinical study reports had no individual patient listings and
"this begs the question of how many more adverse events would have been revealed
if [these] were available for all trials, and raises concerns why this
information is allowed to be withheld."
Link to research
Link to editorial
Additional information about antidepressant trial data added to this blog February 2017
Restoring Study 329 - The study
that disproved anti-depressants’ efficacy
A major
reanalysis of the infamous clinical trial, Study 329, has shown Paroxetine
(also known as Paxil or Seroxat), one of the most commonly prescribed
antidepressants, to be unsafe and no more effective than a placebo.
This new
assessment directly contradicts the results of the clinical trial that claimed
Seroxat to be “generally well tolerated and effective”, which was sponsored by
and ghostwritten for GlaxoSmithKline, despite using the same original data.
The
latest paper was published under the restoring invisible and abandoned trials
(RIAT) initiative, in order to re-evaluate any conclusions drawn from evidence
that had previously been hidden from public view.
Published
in 2001, Study 329 generated a high level of controversy from patients and
doctors after lawsuits were filed stating the side-effects were much more
serious than those documented in the clinical trials.
Restoring
Study 329, showed Paroxetine (Seroxat or Paxil) to have no significant
reduction of depressive symptoms more than a placebo or previous
anti-depressants, and gave users a higher chance of psychiatric side effects.
The
original study came under intense scrutiny following revelations that it was
ghost written by GSK authors and not those named on the study, and the primary
data was not made publically available.
The
findings of Study 329, originally published in 2001, was the first double blind
patient study to report the efficacy of anti-depressants on adolescents.
It has
allowed Seroxat to gain widespread approval by the healthcare industry,
becoming the most widely prescribed anti-depressant in the US, with over
14 billion dolllars worth of sales between 1997 and 2004.
Following
a decade of public and legal pressure, GSK finally released the original data
to the public, making its reanalysis possible.
These
devastating results overturning the original paper may come as no surprise to
many who have already suffered loss and harm from the drug. In 2012 GSK were successfully sued $3 billion
for fraudulently promoting Paroxetine to the public, and hiding key data in its
study, such as reclassifying suicidal acts so that they would not count in the
final analysis.
To this
day however, GSK remain silent on the issue and continue to promote the drug to
its customers, without any attempt to acknowledge the restoration of the study.
A personal note
to our readers:
As we
reveal these facts about Seroxat, we do not wish to condemn all use of
anti-depressants nor encourage the immediate withdrawal from the medication. It is important to obtain advice from
responsible health professionals who can help to plan any reduction in drugs
that may cause dependence. It is also important to inform those close to you
when you plan to start, reduce or stop taking antidepressants.
We wish
to highlight the potential dangers and risks of Paroxetine and similar
medication, and let readers understand that medical information to support the
drug can be unreliable or biased.
Both
starting and coming off anti-depressants is a serious undertaking and we
strongly advise that users seek professional medical help as well as inform
either close friends or family when doing so, as it can be a tough process
which needs careful monitoring and support.
We
recommend considering talking therapy and CBT to those who have access to these
services, as these have been shown to provide beneficial reductions of
depression and anxiety with fewer and less serious side effects.
©JBforAPRIL
Article
on Study 329
British
Medical Journal Analysis of Study 329
David
Healy’s website on the controversy of Study 329
Restored
Study 329
