BMJ  2004;329:1350 (4 December), doi:10.1136/bmj.329.7478.1350

reviews

Book

Medicines out of Control? Antidepressants and the Conspiracy of Goodwill

The treatment of depression has seldom been more controversial. The safety of new antidepressants is subject to radical reappraisal, while an unpleasant question looms: can we really trust scientific evidence? Medawar and Hardon give a detailed analysis of this quagmire, massively annotated with footnotes and verbatim quotations.

It is understandable that the references sometimes get lost or the argument wanders, for the problem is not focal but pervasive. Theirs is an indictment of "big pharma" (the drug industry), doctors (both as prescribers and researchers), the regulatory authorities, politicians, and, ultimately, the values of society itself. Building on the evidence that earlier treatments of "distress" (such as opium, barbiturates, and benzodiazepines) initially seemed benign, only to wreak havoc later, the authors locate a similar optimism among early accounts of some antidepressants (particularly the selective serotonin reuptake inhibitors or SSRIs).

However, they suggest that there is something different about the current debate—something that is about precision, semantics, or sleight of hand, depending on your viewpoint. The authors argue that SSRIs elicit "dependency," as evidenced by withdrawal phenomena, but that this has been obfuscated by terminology. If feeling worse or experiencing adverse reactions when stopping a drug constitutes dependence, then SSRIs produce it. However, an alternative vocabulary describes such withdrawal phenomena (note the connotation of addiction) as "discontinuation" reactions, a softer sounding term. Furthermore, classically dependence requires euphoria and tolerance (increasing the dose to get the same effect). SSRIs evoke neither of these phenomena, but the authors see this as special pleading.

They extend their critique to the failure of post-marketing surveillance procedures. Relatively few prescribers report adverse reactions, and low levels of reporting can foster the assumption that little is wrong. The authors term this the NERO (no evidence of risk equals evidence of no risk) fallacy.

Again, their question is whether the people monitoring the unwanted effects of SSRIs knowingly or unknowingly minimised the drugs' drawbacks. If these drugs encourage suicidal acts among some patients then calling such acts "non-accidental" really matters. The authors suggest that the classification of suicidal acts as non-accidental obscured the problems with paroxetine in particular. Here, much depends on the attribution of motives to others.

Throughout the book the authors describe detailed paper trails: naming names and meetings, quoting what the regulators said, who gave evidence, who declared an "interest" and left the room, who had shares in drug companies. A number of psychiatrists are named. A dilemma emerges. A committee needing an expert opinion will need someone who has worked in the area. Yet a psychopharmacology researcher may well have received grants from industry. If the expert leaves the room when the science is discussed (declaring a competing interest), then the level of discourse is diminished. Few recognised experts in psychopharmacology have never interacted with big pharma. This critique sees all such contact as evidence of potential collusion. Yet we know that clinical research would be a long time coming if it depended only on scarce "blue chip" funding such as the Medical Research Council or Wellcome.

All the major players can be seen as compromised. The drug companies are massive organisations that need reform (see BMJ 2004;329: 862[Free Full Text]) yet are struggling to innovate. Most new compounds are variations on a theme; and, paradoxically, most research occurs within the public sector.

Elsewhere, the academic research community needs money to survive. Universities encourage entrepreneurship, and research income is a major determinant of esteem. Commerce is not confined to psychopharmacology; some genetics presentations are based on data that cannot be shown because of patent issues. It is not inconceivable that the pursuit of truth might eventually be constrained by the bottom line and science "deprived of its epistemological character" (R Horton, "The dawn of McScience," New York Review of Books, 2004 March 11: 7-9). And prescribers are no better. Social psychological research has repeatedly shown that doctors misjudge the influence exerted on them by big pharma's gifts and representatives. We are all fallible.

The regulators work closely with industry; governments encourage this and often the same people rotate between sectors (poacher or gamekeeper by turns). Even patients' groups may be financed by industry.

Medawar and Hardon also emphasise what will be familiar to those who attend journal clubs: that published research is often of poor quality, and data may be deployed creatively. As Richard Horton, the editor of the Lancet, says in the New York Review of Books article, "Journals have devolved into information-laundering operations for the pharmaceutical industry."

This is a depressing book, offering few solutions. The last pages invoke Ivan Illich and his thesis that medicine is bad for society, fostering dependence on doctors and technology and robbing us of our autonomy—our belief in ourselves as basically healthy, capable human beings. My own view, for what it is worth, is that where national governments fund health care they have a legitimate interest in properly funding research into treatment. Until they do we will rely on committees sifting inadequate studies and meta-analyses of secondhand data.

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University of Sheffield s.a.spence{at}sheffield.ac.uk

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Competing interests: SAS has received honorariums from drug companies for chairing meetings and making scientific presentations (all income donated to department funds); has received research grant funding from Cephalon UK, and has been supported in attending conferences and scientific symposiums. SAS does not accept personal payments, does not give promotional talks, and does not own shares in drug companies. He holds an MRC career establishment grant.

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