Transcript Why were doctors so slow to recognise antidepressant

Why were doctors so slow to
recognise antidepressant
discontinuation problems?
D B Double
Defeat depression campaign
Five-year national
campaign launched Jan
1992 by Royal College
of Psychiatrists in
association with Royal
College of General
Practitioners
Defeat depression campaign
Five-year national
campaign launched Jan
1992 by Royal College
of Psychiatrists in
association with Royal
College of General
Practitioners
To educate health
professionals and public
and reduce stigma
Defeat depression campaign
Door-to-door survey of
public opinion before
the campaign started
Defeat depression campaign
Door-to-door survey of
public opinion before
the campaign started
Most of the sample
(78%) thought that
antidepressants were
addictive
Defeat depression campaign
Patients should be
informed clearly when
antidepressants are first
prescribed that
discontinuing treatment
in due course will not be
a problem
Warning in British National
Formulary since 1990
Symptoms may occur if
an antidepressant is
stopped suddenly after
regular administration
for 8 weeks or more.
Warning in British National
Formulary since 1990
Symptoms may occur if
an antidepressant is
stopped suddenly after
regular administration
for 8 weeks or more.
Case reports of
discontinuation
reactions have
appeared since
antidepressants were
first introduced
Serotonin specific reuptake
inhibitors (SSRIs)
New class of
antidepressants
introduced into the
market in 1987
Serotonin specific reuptake
inhibitors (SSRIs)
New class of
antidepressants
introduced into the
market in 1987
Discontinuation
symptoms only
recognised after the
SSRIs had been in
widespread clinical use
for several years
Recognition of antidepressant
discontinuation reactions
Consensus meeting
sponsored by Eli Lilly in
Phoenix, Arizona, at
end of 1996
Recognition of antidepressant
discontinuation reactions
Consensus meeting
sponsored by Eli Lilly in
Phoenix, Arizona, at
end of 1996
Preventable and simple
to treat (BMJ editorial
1998)
Recognition of antidepressant
discontinuation reactions
Discontinuation
symptoms are common
(Letter to Lancet 2000)
Recognition of antidepressant
discontinuation reactions
Discontinuation
symptoms are common
(Letter to Lancet 2000)
GlaxoSmithKline
dropped its insistence
that paroxetine is not
addictive in 2003
NICE guideline for depression
2004
All patients prescribed
antidepressants should
be informed that
discontinuation/
withdrawal symptoms
may occur on stopping,
missing doses or,
occasionally, on
reducing the dose of the
drug.
Nature of antidepressant
discontinuation reactions
No accepted definition
of an antidepressant
discontinuation
syndrome
Nature of antidepressant
discontinuation reactions
No accepted definition
of an antidepressant
discontinuation
syndrome
Commonly seen as
related to re-regulation
of receptors and
transporters
Psychological dependence
Negative affect
experienced in absence
of the drug
Psychological dependence
Negative affect
experienced in absence
of the drug
People may form
attachments to their
medications more
because of what they
mean to them than what
they do
Psychological dependence
Patients often stay on
medications, maybe
several at once, even
though their actual
benefit is questionable
Psychological dependence
Patients often stay on
medications, maybe
several at once, even
though their actual
benefit is questionable
Any change threatens
an equilibrium related to
a complex set of
meanings that their
medications have
acquired
Doctor does not know best
A drug which is thought
to improve mood is
likely to be habit
forming, so however
much the medical
profession may declare
that antidepressants are
not primarily reinforcing
like psychostimulants,
the public understands
that there may be
problems discontinuing
antidepressants
Reasons for defensiveness about
discontinuation problems
(1) Doctors concentrate on
short-term rather than
long-term treatment
Reasons for defensiveness about
discontinuation problems
(1) Doctors concentrate on
short-term rather than
long-term treatment
(2) Doctors focus on
neurobiological rather
than psychosocial
factors
Reasons for defensiveness about
discontinuation problems
(1) Doctors concentrate on
short-term rather than
long-term treatment
(2) Doctors focus on
neurobiological rather
than psychosocial
factors
(3) Doctors are biased
about the effectiveness
of medication
(1) Doctors concentrate on shortterm rather than long-term treatment
Medication is often
prescribed in life crises
reinforcing defensive
mechanisms against
overwhelming anxiety
(1) Doctors concentrate on shortterm rather than long-term treatment
Medication is often
prescribed in life crises
reinforcing defensive
mechanisms against
overwhelming anxiety
Power of placebo
should be recognised
(1) Doctors concentrate on shortterm rather than long-term treatment
We all want a simple,
quick, cheap, painless,
and complete cure.
(1) Doctors concentrate on shortterm rather than long-term treatment
We all want a simple,
quick, cheap, painless,
and complete cure.
People express
reluctance to take
drugs, but an inability to
be free of them
(1) Doctors concentrate on shortterm rather than long-term treatment
There is nothing men will not do
… to recover their health and save
their lives. They have submitted to
be half drowned in water, … half
choked with gases, … buried up to
their chins in earth, … seared with
hot irons like galley slaves, …
have needles thrust into their
flesh, and bonfires kindled on their
skin, to swallow all sorts of
abominations, and to pay for all
this, as if blisters were a blessing
and leeches were luxury. What
more can be asked to prove their
honesty and sincerity? Oliver
Wendell Holmes (1842)
(1) Doctors concentrate on shortterm rather than long-term treatment
Mean duration of trials
in NICE analysis of
SSRIs vs placebo =
6.75 weeks
(1) Doctors concentrate on shortterm rather than long-term treatment
Mean duration of trials
in NICE analysis of
SSRIs vs placebo =
6.75 weeks
Episodic nature of
depression means that
episodes seem easy to
treat
(1) Doctors concentrate on shortterm rather than long-term treatment
Discontinuation trials of
antidepressants have a
substantial relapse rate
(92% to 36%)
(1) Doctors concentrate on shortterm rather than long-term treatment
Discontinuation trials of
antidepressants have a
substantial relapse rate
(92% to 36%)
Long term prognosis in
depression is not good
– only 1/5th recovered
after 15 years
(1) Doctors concentrate on shortterm rather than long-term treatment
Distinguishing
discontinuation reaction
from true relapse is not
always clear-cut
(1) Doctors concentrate on shortterm rather than long-term treatment
Distinguishing
discontinuation reaction
from true relapse is not
always clear-cut
Expectations are as
likely to play a role in
discontinuing
medication, producing a
nocebo reaction
(1) Doctors concentrate on shortterm rather than long-term treatment
Some evidence that
people treated without
antidepressants may do
better over the long
term
(1) Doctors concentrate on shortterm rather than long-term treatment
Some evidence that
people treated without
antidepressants may do
better over the long
term
Could antidepressants
create a vulnerability to
relapse?
(2) Doctors focus on neurobiological
rather than psychosocial factors
Commonly believed that
mental illness is due to
chemical imbalance
(2) Doctors focus on neurobiological
rather than psychosocial factors
Commonly believed that
mental illness is due to
chemical imbalance
No rigorous
corroboration of the
serotonin theory of
depression, and a
significant body of
contradictory evidence
(2) Doctors focus on neurobiological
rather than psychosocial factors
[No] discernible pathological
lesions … that in or of
themselves serve as reliable
or predictive markers of
mental disorder
(2) Doctors focus on neurobiological
rather than psychosocial factors
[No] discernible pathological
lesions … that in or of
themselves serve as reliable
or predictive markers of
mental disorder
BUT mental disorders will
eventually be proven to
represent disorders of
intercellular communication
or disrupted neural circuitry
APA (2003)
(2) Doctors focus on neurobiological
rather than psychosocial factors
People are able to
understand that the
“chemical imbalance
theory” is only a theory
(2) Doctors focus on neurobiological
rather than psychosocial factors
People are able to
understand that the
“chemical imbalance
theory” is only a theory
What they may find
more difficult to
appreciate is why they
are told that this theory
has been proven, when
this is not the case
(2) Doctors focus on neurobiological
rather than psychosocial factors
Chemical imbalance
theory is used as a
means of persuading
patients to take
medication
(2) Doctors focus on neurobiological
rather than psychosocial factors
Chemical imbalance
theory is used as a
means of persuading
patients to take
medication
People require the
expertise of doctors to
make sense of the
information available to
them
(2) Doctors focus on neurobiological
rather than psychosocial factors
Insanity is "a corporeal disease".
… I have never been able to
conceive … a disease of the
mind.
(2) Doctors focus on neurobiological
rather than psychosocial factors
Insanity is "a corporeal disease".
… I have never been able to
conceive … a disease of the
mind.
[T]he various and discordant
opinions, which have prevailed
in this department of knowledge,
have led me to disentangle
myself as quickly as possible
from the perplexity of
metaphysical mazes. Haslam
(1798)
(2) Doctors focus on neurobiological
rather than psychosocial factors
View that the phenomena
of human existence can be
understood in exclusively
biological terms is
obviously attractive
(2) Doctors focus on neurobiological
rather than psychosocial factors
View that the phenomena
of human existence can be
understood in exclusively
biological terms is
obviously attractive
It is legitimate to question
whether an understanding
of human nature can take
the same form as the laws
of natural science
(2) Doctors focus on neurobiological
rather than psychosocial factors
Biomedical hypothesis is
so fundamental to the
edifice of psychiatry that
“chemical imbalance”
theory is still believed
despite contrary evidence
(2) Doctors focus on neurobiological
rather than psychosocial factors
Biomedical hypothesis is
so fundamental to the
edifice of psychiatry that
“chemical imbalance”
theory is still believed
despite contrary evidence
At its most extreme,
biomedical psychiatry
reduces the person to a
brain that needs its biology
cured.
(2) Doctors focus on neurobiological
rather than psychosocial factors
Suggesting mental illness
has a physical basis
serves as the justification
for psychiatric
interventions and
institutions
(2) Doctors focus on neurobiological
rather than psychosocial factors
Suggesting mental illness
has a physical basis
serves as the justification
for psychiatric
interventions and
institutions
In the UK prescriptions for
antidepressants almost
tripled in the 11 years up to
2002
(2) Doctors focus on neurobiological
rather than psychosocial factors
Patients may want
antidepressant
prescription, but doctors
do not appreciate how
much they may not
(2) Doctors focus on neurobiological
rather than psychosocial factors
Patients may want
antidepressant
prescription, but doctors
do not appreciate how
much they may not
Doctors should not
deceive their patients
(3) Doctors are biased about the
effectiveness of medication
Results of thousands of
studies of antidepressants
are not nearly as
conclusive as they are
often claimed to be
(3) Doctors are biased about the
effectiveness of medication
Results of thousands of
studies of antidepressants
are not nearly as
conclusive as they are
often claimed to be
About a third of published
studies show no
difference between
antidepressants and
placebo
(3) Doctors are biased about the
effectiveness of medication
Negative studies of
antidepressants may not
be published
(3) Doctors are biased about the
effectiveness of medication
Negative studies of
antidepressants may not
be published
Even in the trials that are
published, outcomes are
not always reported,
particularly if the findings
are negative
(3) Doctors are biased about the
effectiveness of medication
Conclusions in trials
funded by drug
companies tend to be
more positive
(3) Doctors are biased about the
effectiveness of medication
Conclusions in trials
funded by drug
companies tend to be
more positive
Better quality studies are
associated with less
treatment effect
(3) Doctors are biased about the
effectiveness of medication
Mean drug–placebo
difference in improvement
scores of 1.8 points on the
Hamilton Rating Scale of
Depression
(3) Doctors are biased about the
effectiveness of medication
Mean drug–placebo
difference in improvement
scores of 1.8 points on the
Hamilton Rating Scale of
Depression
Statistically significant, but
of marginal clinical
significance (National
Institute for Health and
Clinical Excellence NICE)
(3) Doctors are biased about the
effectiveness of medication
Expectation that
medication will produce
improvement may itself
produce apparent benefit
(3) Doctors are biased about the
effectiveness of medication
Expectation that
medication will produce
improvement may itself
produce apparent benefit
To prevent expectations
influencing outcome the
trial is conducted
“double-blind”
(3) Doctors are biased about the
effectiveness of medication
Randomised clinical trials
are not as "double-blind"
as is commonly assumed
(3) Doctors are biased about the
effectiveness of medication
Randomised clinical trials
are not as "double-blind"
as is commonly assumed
Subjects and doctors may
be cued in to whether
subjects are taking active
or placebo medication
(3) Doctors are biased about the
effectiveness of medication
Both doctors and subjects
can guess treatment more
accurately than would be
predicted by chance
(3) Doctors are biased about the
effectiveness of medication
Both doctors and subjects
can guess treatment more
accurately than would be
predicted by chance
Degree of unblinding
correlates with treatment
effect
(3) Doctors are biased about the
effectiveness of medication
Effect size also correlates
with proportion of patients
having side effects
(3) Doctors are biased about the
effectiveness of medication
Effect size also correlates
with proportion of patients
having side effects
Raters' expectations and
patients' suggestibility
could entirely explain the
small effect size
(3) Doctors are biased about the
effectiveness of medication
Doctors do not generally
tell patients about small
effect size and substantial
non-response rate of
antidepressants for fear of
undermining effectiveness
(3) Doctors are biased about the
effectiveness of medication
Doctors do not generally
tell patients about small
effect size and substantial
non-response rate of
antidepressants for fear of
undermining effectiveness
Questioning the
effectiveness of
antidepressants is
legitimate
Conclusion
Perhaps not that surprising
that doctors were slow to
recognise antidepressant
discontinuation reactions,
as focus too much on shortterm fix, not psychologically
minded and too quick to
peddle medication
Conclusion
Perhaps not that surprising
that doctors were slow to
recognise antidepressant
discontinuation reactions,
as focus too much on shortterm fix, not psychologically
minded and too quick to
peddle medication
Not all doctors fit this
stereotype
Conclusion
Psychiatry can be practised
without the justification of
postulating brain pathology
as the basis for mental
illness
Conclusion
Psychiatry can be practised
without the justification of
postulating brain pathology
as the basis for mental
illness
Mental disorders must show
through the brain but not
always in the brain
Conclusion
"Psychiatry is naked," the
child said.
Psychiatry could not admit
to that. It thought it better to
continue the procession
under the illusion that
anyone who couldn't see its
clothes was either stupid or
incompetent