Before Prozac
Authors: J. John Mann
Journal: Journal of Clinical Investigation (2009)

In the evocatively titled Before Prozac: the troubled history of mood disorders in psychiatry, Edward Shorter — the Hannah Professor in the History of Medicine and Professor of Psychiatry at the University of Toronto — provides a history of psychopharmacology and a docudrama that present his view of the roles of the pharmaceutical manufacturing industry and the FDA in the development of new drugs and as catalysts in the decline of their use as their patents expired and, with them, profits from their sale. Writing in a lively, exciting style packed with historical facts, Shorter brings to life the process of psychiatric drug discovery and development, enriching the fabric of his narrative with details about the persons involved. He begins with opiates, cocaine, and sedatives and later discusses antipsychotics and tricyclic antidepressants. From this perspective, the book is a lot of fun to read. 

However, what this reviewer believes makes this book hazardous to one’s scientific health are a series of statements that fly in the face of much scientific evidence. For example, Shorter states that selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants known to be inferior to tricyclic antidepressants and that the field has been encouraged by industry to utilize SSRIs because the patents have expired on tricyclics and they therefore generate less revenue. While profit is one motive driving pharmaceutical companies, marketing unsafe or ineffective medications also undermines profit and credibility and many industry researchers are dedicated to finding safer, more effective medications. The fact that helping patients can also be profitable does not mean that industry’s actions are not in the public interest or without real value in terms of improving medical care. It is possible for the pharmaceutical industry to both seek a profit and serve the public good, and this is a lot closer to the reality than Shorter would have us believe.

Shorter also questions the psychiatric diagnostic system. We are asked to ignore the advantages of a diagnostic system with defined criteria. Even if one disagrees with the criteria as the author does, at least diagnostic criteria provide a common language and allow much greater confidence when comparing results of different studies. It is unrealistic to think that loosely described, impressionistic clinical observations in patient groups would be better than the set of widely used diagnostic criteria in place today.

Shorter also describes a push for more power by the FDA, which he ascribes to a basic government instinct to seek more regulatory authority and not to any high-minded effort to improve the approval process for new drugs and devices based on how well they work or how safe they are. Shorter does not concede advantages in terms of decreased risk of tardive dyskinesia for newer versus older antipsychotics or decreased risk of tricyclic-induced adverse cardiac conduction effects that are not found in newer antidepressants. He also dismisses concerns over the addictive properties of sedatives and attributes congressional concerns over their soaring prescription rates in the 1950s and 1960s as “a political reaction,” betraying little appreciation for what has been learned about drug addiction.

A theme in the book is that older drugs, for which efficacy data involved fewer randomized controlled trials and often small samples, are better than newer drugs that have been more rigorously tested. Shorter does not highlight for the reader that there have been studies comparing old and new antidepressants and that it is far from clear that there is any difference in efficacy. The author’s enthusiasm for drugs that were developed years ago, as well as a lack of acknowledgement that a reduction in side effects was a major factor in the shift from using tricyclics to new SSRIs, is perplexing. The chances of surviving a suicide attempt using an SSRI are much greater than those of surviving an overdose of a tricyclic. Pediatric depression does not respond to tricyclics but has been shown to respond to the SSRI fluoxetine. Given that pediatric depression is the main cause of youth suicide — the third leading cause of death in teenagers and young adults — it is preferable to use SSRIs in that age group.

In Shorter’s mind, the FDA forced the use of diagnostic criteria that are not as good as criteria from years ago, and according to the author, many of the patients falling into the newer criteria are not really ill. If these patients are not really ill, why is depression moving toward the top of the list of diseases in terms of disease burden? Shorter believes that for a variety of different reasons, the FDA and the pharmaceutical industry have created a situation in which many patients as well as individuals who are not really ill are being treated with medications that are not as good as those in use decades earlier. The scientific literature tells a different story.