Edward Shorter, The Rise and Fall of the Age of Psychopharmacology

New York: Oxford University Press; 431 pages

Reviewed by Edward Shorter



        The book covers major developments in psychopharmacology since the field was born in the 1950s.  Chapters include laying a scientific basis for psychopharmacology, the rise of interest in industry, scientific developments, the DSM, several chapters on marketing, several more chapters on clinical trials,  a chapter on academics who have aided in marketing (sometimes referred to as “KOLs,” or Key Opinion Leaders), the involvement of the FDA and the failure of the field in the last 40 years to come up with molecules having novel mechanisms of action.  Among the sources are: testimony and documents produced in legal discovery proceedings, emails and such blogs as Mickey Nardo’s “One Boring Old Man,” and private communications with the author.


Author’s statement

        Many psychiatrists are extraordinarily effective clinicians,  but they act in a way that has little scientific underpinning.  Psychiatry has largely lost its scientific basis.  So, for psychiatry as a medical discipline, there is a crisis.  The field lacks the kind of science that the rest of medicine has:

  1. Doubts about the diagnoses, which do not correspond to real disease entities as found in Nature (e.g., “major depression,” “schizophrenia,” bipolar disorder,” etc.).
  2. Doubts about the treatments, which are either largely inert (SSRIs) or toxic in the wrong populations (SGAs in paediatric use or in the elderly).  A number of clinicians believe thar the SSRIs and TCAs are equipotent and prescribe Prozac because it is thought to have fewer side effects.  But the literature suggests otherwise:  there has never been a trial in serious depression where the SSRIs and TCAs have come out even. 

        The most powerful treatment in psychiatry is convulsive therapy, which, ironically, many psychiatrists shy away from.

  1. Doubts about the proposed mechanisms of action, namely, neurotransmitter theory.  This theory constitutes the intellectual platform of the field – the idea that the metabolism of the amine neurotransmitters determines behavior.  This idea turns out to be bankrupt.

        Of course, discovering the reuptake mechanism was a major scientific advance.  But it was not a clinical advance.  Knowledge of neurotransmitters has contributed very little to clinical psychiatry over the past half century.

        The result of all three of these circumstances:   there have been no drugs with novel mechanisms discovered for the last 40 years.



  1. Much more interest in identifying the real phenotypes is needed.  This will help get drug discovery going again.  As they say, “You can’t discover drugs for diseases that don’t exist.”
  2. There is a need to downplay interest in the amine neurotransmitters (serotonin, dopamine, etc.).  By contrast, interest should be revived in such physiological measures of brain activity as pharmaco-EEG.
  3. Take DSM away from the APA, which is a trade guild.   A scientific organization such as NIMH or the Karolinska Institut would start from scratch and do a much better job.


December 9, 2021