Despite recent evidence suggesting
that anti-depressants might be quite harmful, Canadian
authorities are conducting their studies slowly and in
(Cold water thrown on Prozac
Over the past few weeks and months, there has been shock
after shock as ordinary people scramble to make sense of how
the world's most popular anti-depressants are suddenly being
described by regulators as ineffective and perhaps even
Twenty years after the first selective serotonin reuptake
inhibitor or SSRI was approved for adult use, we're being told
that there has long been evidence indicating that these
anti-depressants may be no more effective than sugar
We've learned that, especially among young people, the
risks of taking the drugs may outweigh the benefits. The
British regulatory authority is now concerned enough about the
adult risks that it launched a study this week to determine
whether the drugs are safe.
What we may be seeing is the beginning of the end for the
Prozac Nation -- even if Prozac isn't the specific target.
When Prozac and its SSRI cousins came to market 20 years
ago, depression was rarely diagnosed. Now, everybody seems to
be depressed and the treatment of choice is drugs not
Nearly 31 million prescriptions for anti-depressants were
written in Canada in 2002. And SSRIs are usually the drug of
choice. Billions of dollars worth are sold worldwide
-- nearly 14 million SSRI prescriptions were written in
Canada alone last year at a cost of $869 million.
The bad news started in Britain. Last spring, regulators
warned of the increased suicide risks for children taking
paroxetine -- sold as Seroxat in Britain and Paxil in North
America. Canadian and American regulators followed with
warnings about Paxil and its cousin, Effexor or
Last month, Britain went further. After analyzing
previously unpublished clinical trial data, it banned doctors
from writing any new prescriptions of any SSRIs -- except
Prozac -- for anyone 18 or younger.
There was no immediate response from either Health Canada
or the U.S. Food and Drug Administration. Both are still
studying new information drug companies provided them last
Neither has responded to Britain's new study into the risks
SSRIs pose to adults. Over the coming months, British
researchers will look at a group of patients of all ages --
the oldest is 90 -- who were diagnosed with depression between
1995 and 2001. The aim is to estimate the risk of suicide,
suicidal thoughts, non-fatal overdoses and self-laceration in
patients treated with both SSRIs and tricyclic
Tricyclic anti-depressants are a large class of older
medications including amitriptyline (Elavil), imipramine
(Tofranil), clomipramine (Anafranil), nortriptyline
(Norventyl) and desipramine (Norpramine) that are now
available in generic versions. Because their patents have
expired, they are much, much cheaper than SSRIs.
Dr. Jane Garland, head of the mood disorders clinic at B.C.
Children's Hospital, says the tricyclics are the "gold
standard" anti-depressants, and may be more effective than
SSRIs for severe depression.
Despite that, she says, SSRIs have replaced them as
first-line medication, with tricyclics being used in more
treatment-resistant cases. Garland goes on to say that because
the older drugs have much more serious and unpleasant side
effects than SSRIs, "they were used more conservatively than
While British regulators were making their announcement
last week, the Wall Street Journal reported on Canadian
research that offers an explanation for why nearly 80 per cent
of people treated for depression with drugs relapse, compared
with just 25 per cent of those who completed a full course of
Led by neuroscientist Helen Mayberg of the Rotman Research
Institute and the University of Toronto, the researchers
determined that psychotherapy -- the so-called talk
therapy popularized by comedian Woody Allen -- and
anti-depressants work in completely different ways and on
different parts of the brain.
The drugs reduce activity in the brain's emotion centres or
limbic system, while cognitive-behavior therapy quiets
overactivity in the cortex.
The Toronto study -- partially funded by the federally
supported Canadian Institute for Health Research -- should
lead doctors, health administrators and politicians to
question why so much more money is being spent on drug
therapies for depression than on the more effective
It should also lead them to ask why more primary-care
doctors -- who write the majority of prescriptions for
antidepressants -- aren't trained in psychotherapy.
Although with health being split over so many
jurisdictions, there's not a great deal of room for optimism
that anything will change quickly.
But back to SSRIs and Health Canada. When Health Canada
completes its review of the pediatric trial data that it
received last fall, the government plans to appoint an expert
advisory panel that will begin closed door meetings sometime
There the experts will take a look at the Health Canada
review, look at the conclusions of the British regulators
regarding pediatric SSRI prescriptions and any information
from the new British investigation.
The experts will also analyze what is said at the U.S. Food
and Drug administration's Feb. 2 meeting. There in an open
forum, experts, drug company officials and others will talk
about both pediatric and adult use of SSRIs.
But even after the Canadian panel completes its review, it
can only make recommendations to Health Canada. It could, for
example, follow the British regulators and ask for labelling
that says some or all of the SSRIs are not to be prescribed
for patients 18 and younger.
Before any labelling changes are made, Health Canada must
meet with the drug companies to reach a consensus on what that
labelling should say.
While for most people, the regulators' recent interest in
the multi-billion-dollar, anti-depressant business seems
sudden, many experts can't believe it's taken so long.
One of those experts -- Dr. Irving Kirsch of the
University of Connecticut -- asked nearly two years ago
why the American regulators had approved the drugs in the
Irving and four colleagues re-analyzed the SSRI's efficacy
data presented by the companies to the FDA between 1987 and
1999 for approval of the six most widely prescribed
antidepressants -- Prozac (fluoxetine), Paxil (paroxetine),
Zoloft (sertraline), Effexor (venlafaxine), Serzone
(nefazodone) and Celexa (citalopram).
They found that nearly 80 per cent of the response to the
anti-depressants was duplicated in the patients receiving
sugar pills, not drugs (i.e., the SSRIs were no more effective
They also found that the rate of improvement in patients
receiving the highest doses was not any different than the
improvement rates among those receiving lower doses. And they
found errors in the way the data were reported and analyzed.
Kirsch et al concluded: "To the extent that these data are
flawed, the medications should not have been approved."
If it didn't set off regulatory alarm bells for the
regulators, it should have for prescribing doctors -- all of
whom had easy access to the analysis that was published in the
American Psychological Association's July 2002 edition of
Prevention & Treatment.
Apparently, doctors weren't alarmed either.
The number of Canadian prescriptions for SSRIs increased in
2002 (up nearly 14 per cent) and is keeping about the same
pace for the first 10 months of 2003.
While it is heartening that governments are finally
recognizing the need to revisit their approvals of SSRIs,
Canadians need to join the chorus of experts asking why a full
review has taken so long and why now that Canada is doing that
review, it's being held in secret.