Antonio E. Nardi, Richard Balon, Guy Chouinard, Fiammetta Cosci, Steven Dubovsky, Giovanni A. Fava, Rafael C. Freire, David J. Greenblatt, John H. Krystal, Karl Rickels, Thomas Roth, Carl Salzman, Richard I. Shader, Edward K. Silberman, Nicoletta Sonino, Vladan Starcevic and Steven J. Weintraub: The value of long-term clinical experience with benzodiazepines. International Task Force on Benzodiazepines

Edward Shorter’s comments


            I am highly sympathetic to the efforts of the International Task Force on the Benzodiazepines to rescue this valuable drug class from the ill-informed medical received wisdom of our day.  Yet it might be helpful to bear in mind that, in evaluating the safety and efficacy of drug classes, there are commercial considerations in play as well as scientific.

            The science is clear:  The “benzos” are safe and effective, indeed, after lithium, probably the most effective members of psychiatry’s current armamentarium.

            At the same time, commercial considerations are at work.  When Roche launched Librium in 1960, its advertising copy was keen to differentiate Librium as an “antianxiety” agent, from the “tranquilizers,” by which was meant mainly meprobamate and chlorpromazine.  Thus it passed into the medical received wisdom that the tranquilizers were now out of date, overtaken in safety and efficacy by Roche’s new blockbuster.  And this deafening drumfire of ad copy had a great deal to do with medicine’s quick abandonment of meprobamate and  chlorpromazine as “sedatives."  "Doctor, why sedate your patients when you can relieve their anxiety."  This was commercial hype.

            Don Klein et al. aptly made the point that there is no difference in efficacy among any of these agents and wrote, in the second edition of Diagnosis and Drug Treatment of Psychiatric Disorders: Adults and Children (1980), that “...there is no clear evidence that any of the benzodiazepines, meprobamate-like drugs, or barbiturates is more efficacious than any other.” They did find the barbiturates more dangerous because of the risk of overdose and of addiction.  (In my view this overestimates the risks of the barbiturates, one of psychiatry’s oldest successful drug classes.)

            Then in the late 1960s the FDA staged its Drug Efficacy Study Implementation (DESI) which shrank the indications of chlorpromazine down to psychosis and lost interest in meprobamate entirely.  But DESI was deeply flawed as an exercise and many useful drugs were consigned to the outer darkness on the basis of very little evidence  (but lots of huffy opinions).

            The point is that the history of psychopharmacology is full of useful agents that have been forgotten.  This is partly because of commerce in the form of “counter detailing,” the kind of advertising strategy that Roche used on the tranquilizers.  It is also partly because of a failure on the part of clinical psychopharmacology to convey to primary care physicians that the supposed dangers of the benzodiazepines have been vastly overblown in favor of the SSRIs.

            So, here again we have counter-detailing: the SSRI makers explaining in their ads how dangerous the benzos are and how, ultimately, Prozac and its cousins are preferable in the relief of anxiety.  And, once again, we have a failure of science: accepting at face value the many industry-sponsored trials of the SSRIs and failing to see that psychopharmacology is being vastly manipulated.

            The SSRIs are now all off patent and industry has lost interest in them.  The Next Big Thing will of course explain what a bad idea they were.



Klein DF, Gittelman R, Quitkin F, Rifkin A. DIagnosis and Drug Treatment of Psychiatric Disorders: Adults and Children. Williams & Wilkins, Baltimore, 1980.


May 30, 2019