Daily Mail, Tuesday, August 27, 2019 Page 47WERE FORCED TO REVEAL THEIR FUNDING
to get “completely independent
researchers” on any topic?’ he
asks. ‘Who else is going to pay for
that? Rightly or wrongly, the real-
ity is that all companies pay for the
research on their own products.’
Dr Goldacre’s solution is that we
should legally require all potential
financial conflicts of interest to be
declared fully on an easily
accessible database (see box).
‘Unfortunately, such conflicts are
commonly not disclosed,’ he says.
‘This could be fixed by the medical
profession taking a stand, by policy
makers passing clear rules on
disclosure, and by professional
bodies penalising offenders.’PATIENTS MISS OUT
ON WHOLE PICTURE
The need for complete transpar-
ency is paramount with a drug as
controversial as ketamine.
The potential side-effects, which
include hallucinations, dizziness,
anxiety, psychosis and blood
pressure surges, mean patients
can be given the drug only under
supervision in a clinic room — and
kept there for two hours after
each weekly dose, while being
monitored by staff trained to deal
with hallucinatory, cardiac and
respiratory problems.
Another concern is that scientistsdisagree on how the drug
might work.
In February, Professor Young
wrote a paper in the journal PeerJ
which suggests that ketamine may
work against resistant depression
by inhibiting areas of the brain
associated with troublesome
emotions and memories (he
declared in the journal that he had
no competing interests).
however, Alan Schatzberg, an
eminent professor of psychiatry at
Stanford University in the U.S.,
published a study last year showing
that ketamine works by activating
the brain’s opioid receptors — as
do drugs such as morphine andheroin — which is what can also
make such drugs addictive.
When Professor Schatzberg’s
team introduced a drug that
blocked these opioid receptors
from working, ketamine’s effects
stopped. This suggests a high risk
of becoming addicted to ketamine-
type drugs and subsequently
suffering withdrawal pains.
During several years of trials
sponsored by Janssen, six people
administered esketamine died, as
opposed to none on placebos.
Three deaths were suicides.
The U.S. medicine-licensing
authority, the Food and Drug
Administration (FDA), said it wasdifficult to consider the deaths as
drug-related. however, Professor
Schatzberg says the deaths look
similar to the way addicts kill
themselves during withdrawal
from opioids. Two suicides had
occurred within three weeks of the
patients stopping treatment.
‘To me, these deaths are related
to going off the drug,’ Professor
Schatzberg argues.
Dr McShane is also concerned
about the potential for addiction.
‘Because ketamine makes you feel
better so quickly, when you relapse
you want to take it again,’ he told
reporters in March.
‘When the dosage and frequency
get too high, that’s when it
becomes toxic. It is possible
that people will end up treating
themselves with ketamine obtained
illegally.’ (he is also emphatic that
the drug’s use must be
closely monitored.)
Critics also claim that ketamine-
type drugs have actually failed to
prove their effectiveness in treat-
ing depression. In two out of three
short-term trials sponsored by
Janssen, esketamine proved little
or no better than a placebo at
alleviating depressive symptoms.
Dr McShane’s own Janssen-
sponsored trial on 138 older
patients was not conclusive and
showed the drug to be of benefit
only when the pool of patients in
the trial was narrowed to the
under-75s.
When esketamine was licensed in
the U.S. by the FDA in March, this
was on the basis only of clinical
trials funded and conducted by
Janssen, rather than any con-
ducted independently.
Meanwhile, separate clinical
pilot-projects of ketamine for
depression in Australia and New
Zealand, not funded by Janssen,
were abandoned last year amid
concerns about dangerous side-
effects and lack of effectiveness.WHY THIS
MATTERS TO YOU
IN BRITAIN, esketamine could be
given the go-ahead for depression
under the brand name Spravato as
soon as November. It is currently
being considered by the UK drug
regulator, the Medicines and
healthcare products Regulatory
Agency (MhRA).
however, some worry that keta-
mine could prove a case of history
disastrously repeating itself. Wide-
spread withdrawal problems
associated with conventional SSRI
antidepressants — as highlighted
by Good health — have finally
been acknowledged officially by
UK bodies such as the Royal Col-
lege of Psychiatrists. Could the
medical authorities soon be add-
ing a drug with similar dangers?
Dr James Davies, a lecturer in
psychotherapy at Roehampton
University and spokesman for the
Council for evidence-Based
Psychiatry, which raises awareness
about the harm that can be caused
by psychiatric drugs, told Good
health: ‘We are deeply concerned
about the proposed approval of
esketamine. It works via an opioid
mechanism and is likely to cause
serious problems of addiction
and withdrawal.
‘No one should forget the troubled
history of psychiatric medication,
where supposedly safe and effec-
tive medicines turn out to be
addictive and damaging when used
long term. We urge the MhRA to
deny this drug a licence at least
until long-term trials on safety and
efficacy have been completed.’
Professor Young and Dr Zarate had
not responded to the Mail’s requests
for comment before going to press.
Dr McShane pointed out that in all
discussions with journalists, he
highlights his potential conflicts of
interest. A spokesman for Janssen
said: ‘We actively encourage the
healthcare professionals we work
with to disclose payments that they
have received from both Janssen
and the wider industry.’: Doctors pushing new
have to admit they
by the pill’s makers
show that commercial money
can influence researchers to
sway clinical trials in favour of
the funders’ products.
A study in the British Journal of
Psychiatry in 2017 of 45 trials
comparing talking therapy with
antidepressant therapy found
trials sponsored by drug
companies were consistently
more likely to favour the drugs.
The ABPI figures have prompted
the authoritative Academy of
Medical Royal Colleges to callfor it to be compulsory for Brit-
ish practitioners to disclose
drug-company funding in full — a
campaign that the Daily Mail is
now backing.
The academy’s chairman,
Professor Carrie MacEwen, told
Good Health: ‘Doctors should not
be allowed to opt out of the ABPI
database. As such the system is
fundamentally flawed.’
Since 2013, medical companies
in the U.S. must, by law, detail all
payments to researchers andhealthcare professionals on a
publicly accessible database.
The Council for Evidence-Based
Psychiatry, which campaigns for
responsible prescribing for
psychiatric drugs, is calling for
the UK to follow suit with similar
so-called ‘sunshine’ legislation.
‘Equivalent legislation oper-
ates in France, Australia and the
Netherlands,’ a spokesman told
Good Health.
‘In Britain, it would enable
patients and doctors to under-stand better the relationships
between key opinion leaders
and drug makers.’
A spokeswoman for the
Association of The British Phar-
maceutical Industry, which runs
a database, said: ‘We support all
doctors who disclose the impor-
tant work they do with industry
and urge others to do the same.’
She added: ‘We are constantly
working with the NHS to improve
disclosure rates, in the interests
of transparency for patients.’V1