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Cigarette Smoking,
COPD and Psychological Problems

The use of antidepressants
for smoking cessation in patients with COPD

(thesis)
by
Edwin Wagena
2005

Reviewed by Mira de Vries

"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 critical eye.

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 distinguish between 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 (these figures vary from chapter to chapter) smokers quit smoking when taking one of the 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 the trial.

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 understandable as depending on which statistics you look at. But it’s less understandable why in some chapters he declares the antidepressants practically useless 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 like:
The scandal of unfair behavior of senior faculty
"Do drug 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 of coercion lurking in the background.

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 bad habits? You don’t know what you’re talking about.

We wish to thank Dr. Wagena for the complimentary copy of his thesis.

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