Bitter pills

Medicines out of control? Antidepressants and the conspiracy of goodwill Charles Medawar, Anita Hardon Amsterdam: Aksant; 2004 260 pp US$34.50 ISBN 90 5260 134 8

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Figure. Photo by: Fred Sebastian

From its provocative title, this “narrative about a drug crisis still in the making” proceeds to an analysis of the history of various mood-soothing medicines (opium, cocaine, barbiturates, benzodiazepines and, most recently, SSRIs), whose unexpected adverse effects and potential to induce dependence were either ignored or denied. The content is both controversial and compelling. The authors ask difficult questions about rising prescribing rates for psychotropic medications and about the nature of the relationships between the medical profession, the pharmaceutical industry, researchers and regulatory agencies — the complexity of which may lead to a failure to identify adverse effects and the risk of physiologic dependency. Using common-sense language to convey a well-reasoned and well-referenced approach, the authors clearly intend to reach a broad audience, ranging from students of social science and pharmacy to health professionals and informed members of the public.

What expertise do the authors bring to these issues? Charles Medawar is director of Social Action, a British nongovernmental organization with a focus on policy development and safety regulation that critiques social policy and government accountability. His work, notably that on adverse event reporting, has been published in the peer-reviewed International Journal of Risk and Safety in Medicine. Anita Hardon is a professor of the anthropology of health care. Both perspectives provide insights sometimes lacking within medicine.

Whether or not you agree with the authors' concerns and conclusions, it is a fact that prescription medications for all conditions have become, in most regions, the most rapidly rising medical cost. The authors question whether the arrival of a treatment tends to determine the definition of a disease. Numerous historical examples are given, and Medawar points to the recent proliferation of anxiety disorders in response to the proliferation of SSRIs, each new disorder in the diagnostic manual providing a new indication with the potential to win a patent extension. Recently, this process has been complicated by direct-to-consumer advertising and the funding of patient advocacy and support groups by the pharmaceutical industry. We are also reminded that, a century ago, powerful medications were available without regulatory safeguards. However, regulatory agencies come under the scrutiny of these authors for their possible complicity in minimizing the recognition of adverse effects and for tending to provide speedy drug approval on selected evidence. None of these concerns is being raised here for the first time; all have been highlighted of late in editorials and commentaries in several major medical journals in response to concerns about the way the profession has become embroiled in complex conflicts of interest with the pharmaceutical industry. In Medicines Out of Control? one gets a broader and longitudinal overview of these issues.

Although this is a lively book packed with interesting stories, it does not make for good bedtime reading. For anyone who has not closely followed the checkered history of various mood-altering prescription drugs in the last century, this book will be hard to digest and likely to produce insomnia.

Nevertheless, I recommend this book to physicians of any specialty, particularly those in primary care or psychiatry. It is sobering, challenging and thought-provoking. The title asks a question that we must keep asking ourselves. The subtitle indicates the potential trap. There is no doubt that the medicines reviewed, from opiates and cocaine a century ago to benzodiazepines in the present day, have all been prescribed by caring physicians with a sincere desire to help. But it seems that the same pitfalls repeatedly appear. There is an assumption that sedation or soothing can occur without adverse effects, and there is a consistent minimization or dismissal of the importance of emerging adverse effects or of physiological dependency issues until the evidence becomes overwhelming. Medawar and Hardon present detailed examples of the problems of recognition, reporting and evaluation of adverse effects, pointing out the many flaws in the system that lead to delays in making connections between a medication and serious adverse events. We can be reassured that most of the drugs reviewed have found their appropriate place in the therapeutic armamentarium. But the authors point out that this actually is most likely to happen when a new potential panacea emerges and physicians are ready to let go of the last treatment. The cycle renews itself with remarkably naive optimism on the part of physicians. Typical examples are the rise of heroin after the morphine disappointment and, more recently, the rise of SSRIs after the disillusionment with benzodiazepines.

Is this book relevant to anyone besides an historian of medicine? We pride ourselves in undertaking evidence-based medicine. Yet Medawar and Hardon remind us that our evidence base is often “evidence-biased,” and that in clinical practice our good intentions for rational practice are often outweighed by clinical realities and by the unrealistic hope that medicines will work without doing harm. More importantly, we had better read this book before our patients do and ask us tough questions. The whole thrust here is that physicians and even researchers, being human, have tended to see what they wanted to see and have not listened to contrary evidence. Some would argue that books such as this make it more likely that patients will not take psychiatric medications that they need. In fact, most patients will take seriously the opinion and recommendations of a physician who listens to them, weighs their concerns carefully, is honest about what we truly know and what we don't, and agrees to work collaboratively. We are at greater risk of undermining our credibility with our patients by not considering contrary opinions.

In the past year we have had to come to terms with new information on the effectiveness and adverse effects of SSRIs in young people and with concerns about the delayed recognition of serious adverse effects of medications for other medical conditions. The issues are very much those described by Medawar and Hardon. Getting a longer perspective on these phenomena may be helpful and produce wiser physicians. Therefore, I would also recommend Medicines Out of Control? for medical trainees early in their career. Ideally, however, a reading of the book would be accompanied by a mentor-led group discussion, as its message is so different from what is being received elsewhere, especially at the pharmaceutical-sponsored luncheons into which medical students are quickly initiated. That would be a shame, for those who are ignorant of history are condemned to repeat it.

E. Jane Garland Clinical Professor Psychiatry University of British Columbia Vancouver, BC