The four main SSRI antidepressants
are no more clinically effective than placebo for people with mild
or moderate depression, a meta-analysis in the Public Library of
Science journal reported in February.
The research was front page news
on four broadsheet newspapers as well as BBC and ITV headlines.
The study by psychology professor
Irving Kirsch and colleagues revealed, however, nothing researchers
were not familiar with. Kirsch, when employed in America and using
the same data, had arrived at the same conclusions in a study he
published in Prevention and Treatment journal a full six years previously,
in 2002.
One key difference this time, though,
was Kirsch is now also working at the University of Hull who had
a media-savvy press officer. It was she who publicised the findings
to her UK media contacts, resulting in the blanket coverage. The
study also came at a time when the government is bidding to rid
the UK of the “Prozac nation” slur.
The spiralling number of prescriptions
for anti-depressants hit a record high of more than 31 million in
England in 2006. There were 16.2m prescriptions for SSRIs (selective
serotonin reuptake inhibitors).
Instead the government is turning
to psychological therapies – and is to recruit an extra 3,600
cognitive behavioural therapists to “cure” 450,000 people
with depression and anxiety.
Nevertheless, Kirsch et al’s
study is highly significant. It was based on all drug firm data
– published and unpublished - that the US Food and Drug Administration
(FDA) had used during the eighties and nineties to first approve
four SSRIs, namely fluoxetine (Prozac), venlafaxine (Seroxat), nefazodone
(Effexor), and paroxetine (Serzone).
Kirsch had used freedom of information
law to retrieve the data. A meta-analysis which includes unpublished
trials eliminates “reporting bias” (caused by the same
data being published in several journals) and “selective reporting”
(where only positive outcomes of a drug are published).
Kirsch’s view is clear-cut.
“These [SSRI] drugs should never have been licensed –
that’s the logical response from our study,” he said.
"If one can not draw positive conclusions from the data there
is just no basis to conclude that antidepressants are effective
interventions.”
This view is radically different
to that of the National Institute of Health and Clinical Excellence.
Its 2004 guidelines on depression advises against doctors prescribing
SSRIs to people with mild depression, but states SSRIs are clinically
useful for moderate or severe depression.
Kirsch acknowledges antidepressants
may have some effect for people with severe depression "Antidepressants
may still have a role but we must first think of alternative forms
of treatment," he said. "Antidepressants can be given
to people with severe depression, but only if they don’t manage
to recover from alternative treatment.”
Nice’s guidelines are now
being revised and are to be re-published in June next year. In a
statement, Nice’s clinical and public health director, Professor
Peter Littlejohns, has promised Kirsch's Plos paper will be examined.
But Kirsch’s 2002 paper was scrutinised by Nice in drawing
up its 2004 guidelines.
And the debate by researchers over
whether Nice’s judgement on SSRIs is empirically valid continues.
In The British Medical Journal,
Kirsch and Dr Joanna Moncrieff, a senior lecturer in social and
community psychiatry at University College of London, have criticised
the methodology used by Nice for assessing antidepressant efficacy.
In response, the guidelines’
authors accused Kirsch and Moncrieff of “an inaccurate and
partial reading” of the evidence.
"We believe Moncrieff and Kirsch
have failed…to undermine the evidence base for antidepressants
and to establish their case for a reconsideration of the NICE recommendations
for their use,” they said.
But a new book by Moncrieff, also
an NHS consultant psychiatrist, is likely to up the anti. The book,
entitled the The Myth of the Medical Cure, Moncrieff accuses Nice
of massaging the evidence.
She writes that, when drawing up
its guidelines, Nice conducted a second superfluous statistical
analysis on the data to “present it in such a way that allowed
them [the authors] to draw the conclusions they were comfortable
with.”
A Nice spokeswoman said there was
“no truth” in these accusations.
And in its 2009 guidelines, Nice
is unlikely to change its mind on SSRI efficacy, some experts say.
No more so, they add, because, as
well as the FDA, the UK drug regulator, the Medicine and Healthcare
Products Regulatory Agency (MHRA) has licensed SSRIs for depression.
"It would be highly difficult
for Nice to go against what the drug regulators have decided, says
David Healy, professor in psychological medicine at Cardiff University.
“They could have the drug firms on its back trying to sue.”
Nevertheless, a major concern on
SSRI efficacy is whether scientific objectivity – as well
as public interest and safety - is being compromised by the commercial
muscle of the pharmaceutical industry.
Just days after the Kirsch headlines,
GlaxoSmithKline was rapped by the MHRA for failing to submit studies
which indicated its Seroxat SSRI led to suicidal tendencies in young
people.
The drug, despite not being licensed
for under 18s, was being widely prescribed to them by doctors. The
government says it’s to tighten up the law.
In a letter to GlaxoSmithKline’s
chief executive Jean-Pierre Garnier, MHRA chief executive Kent Woods
said the “moral responsibility” of pharmaceutical firms’
submission of relevant trails needed to be backed up by the “unambiguous
force of law.”
"There is obviously a need
to tighten the law to make it absolutely clear that pharmaceutical
companies have a legal responsibility to inform the regulator of
any information that changes the benefit: risk profile of their
products, regardless of whether the information relates to a licensed
indication,” his letter read.
Health minister Dawn Primarolo says
new legislation will be in place this year to make companies disclose
“any information [on their drugs] they have that would have
a bearing on the protection of health.”
However, Healy fears independent
researchers such as himself will still be unable to scrutinise those
unpublished trials not showing drug efficacy which are submitted
to the MHRA.
He says its vital for this trial
data to be publicly accessible without barriers being put in the
way.
"In some form the drug firm
data needs to available to the public generally, not just the regulators,
ensuring [independent] experts can look at the data,” he says.
"There are good ethical grounds
for doing this. Volunteers who sign up for a drug firm’s clinical
trial would not have got involved if they thought that drug company
would have put away the results.”
A MHRA spokesman said independent
researchers can apply to see drug firm trial data, unless it breaches
commercial or patient information. Will such exceptions be dismantled
under the new law? “We will have to see what is decided in
drawing up the law,” said the MHRA spokesman.
Meanwhile the debate on how best
to treat the various severities of depression goes on.
Exercise, diet, life-changes, and
a plethora of therapeutic interventions are all said to have effect.
Kirsch’s study also again emphasised a significant role of
placebo. And although many mental health charities broadly back
the government’s move to expand cognitive-behavioural therapy,
some campaigners and practitioners claim the focus on CBT is short-sighted.
"If a person’s living
situation is dire, CBT may help them a bit, but it is not going
to improve the situation they are actually in,” says Dr Andrew
McCulloch of the Mental Health Foundation.
Moncrieff says: “CBT is better
than drugs. Giving drugs to people is who are depressed is damaging.
Anti-depressants are psychoactive drugs – its no different
from putting someone on valium.”
Added into the mix are the thousands
of anecdotal accounts praising SSRIs - such as that of Andrew Solomon,
author of The Noonday Demon, a former Mind Book of The Year.
"I have been on Zoloft [Sertraline]for
some years. It’s my experience that is has been demonstratively
life-saving,” he says.
"I also have a less dire view
of the pharmaceutical industry. Without this industry and the profit
motive the drugs would never have been found. I would not be here
if it was not for private enterprise.”
Solomon’s view is opposite
to that of other users. For example, www.seroxatmad.co.uk features
comments from patients on Seroxat which include claims that suicidal
tendencies have been exasperated by the drug.
Anecdotal evidence is fundamentally
different to scientific evidence, it is said. Yet
the scientists fundamentally disagree.
