"You don't know what you're talking about" is a
common response MeTZelf
receives from fresh PhDs who find their name on our (Dutch) web-log.
Articles on medical research by graduates are constantly
marching through our newspapers, as though doctorate
degrees are issued with press releases. Our log's goal is to
stimulate the public at large to view such items with a
Edwin Wagena’s response was a polite variation of the opening sentence
above. Without having
read the thesis, we weren't equipped with the knowledge to criticize
it, he contended. I invited him to send it to us.
It arrived the next day. Already as the book emerged from the envelope,
it became obvious that Wagena’s charge was not unfounded. The newspaper
article had mentioned nothing about COPD – debilitating disease usually
caused by smoking cigarettes. Wagena’s research deals with the haunting
question: how can a patient be kept from smoking himself to death?
Smokers who stop and stay stopped are rare, but, according to his
research, it is even rarer among smokers with COPD. Wagena proposes
that a third element is involved: mental illness, mainly
depression and anxiety. According to his research, these conditions are
significantly more common in smokers with COPD than in other smokers.
Why this is so remains unclear. It’s probably not that having a disease
in itself is depressing, he postulates, because smokers with other
chronic diseases like arthritis or heart disease are less likely to
have a mental illness. On the other hand, it is difficult to
symptoms caused by COPD and those caused by depression. For example,
fatigue and weight loss can be considered symptoms of both.
It could be, the author hypothesizes, that it is the depression which
stimulates smoking in the first place, or that makes quitting so
difficult. Nicotine may have antidepressant properties. If so, it would
be logical that antidepressants help in maintaining smoking abstinence.
Unfortunately, the results are most disappointing. Antidepressants are
only marginally more effective than placebos. Fewer than 9 in 100
vary from chapter to chapter) smokers quit smoking when taking one of
drugs researched, but most of
those nine apparently resumed smoking after six months. For the nine
who quit, albeit temporarily, taking the antidepressant may be better
than dying from COPD. But what about the 91 who didn’t quit? Wagena
doesn’t say. He does note that even these flimsy results are probably
not attainable when the drugs are prescribed by the family physician.
In the trials, the drugs were accompanied by a variety of
non-pharmaceutical interventions, including, in one study, bribing
participants with lottery tickets.
Scant attention is paid in his thesis to the side effects of the
antidepressants. The ones that are mentioned are mild, like dry mouth
and constipation. Is it realistic that among scores of trial
participants, none experienced such serious side effects as tardive
dystonia or violent impulses? Perhaps so, as the two antidepressants
studied were not SSRIs. Wagena does mention that medication compliance
was extraordinarily low.
Perhaps the people with the serious side effects stopped taking the
drug, or dropped out of the study altogether? Of course he does not say
whether the participants who did comply, whether or not they
successfully quit smoking, were able to quit the antidepressants after
One of the difficulties in reviewing Wagena’s thesis, is that except
for the summary, all of the chapters are independent papers which were
either previously published or have been submitted for publication.
This means that there’s quite a bit of overlap, but also a lot of
contradiction. For instance, on page 10, 90% of COPD cases are caused
by smoking, while on page 131, only 75% are. The variation is
as depending on which statistics you look at. But it’s less
understandable why in some chapters he declares the antidepressants
in helping patients to stop smoking, yet in
others concludes that they should be used anyway. Nowhere does he
recommend that a doctor who prescribes an antidepressant to aid in
quitting cigarettes, informs his patient that the chances it will work
are next to nothing, and that he is introducing a new habit which may
be just as hard to break.
Wagena is much aware of ethical issues in research. Throughout his
thesis, he is careful to enumerate possible methodological flaws and
conflicts of interest.
Separately from this thesis, he has (co-)authored papers with titles
scandal of unfair
behavior of senior faculty”
firms hoodwink medical journals?"
"Clinical trials registers are no guarantee that trials are registered"
Yet he cannot completely avoid the
appearance of bias himself. For instance, although he repeatedly
declares that the manufacturers of the drugs he tested did not
contribute funds to his research, on page 4
one of them is listed as a financial supporter of the publication of
his thesis. It appears that modern medical research and pharmaceutical
funding cannot be disentangled. Professional and financial interests
wouldn't matter so much, were there not the ever present specter
lurking in the
Wagena’s book arrived in an envelop carrying the return address of
Solvay, which is also listed as one of the financial supporters of his
thesis. According to the biography in the back, he is employed at
Solvay, and was already at the time he
attained his doctorate. Solvay is surely pleased that the two
antidepressants studied, which are manufactured by its competitors,
were found to be close to useless in the maintenance of smoking
abstinence. You see, Solvay specializes in vaccines. Currently they are
noisily developing a vaccine against ... smoking.
What did you say? Vaccines cannot prevent
You don’t know what you’re talking about.