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


Roger Meyer’s comment on Robert H. Belmaker’s comment (review)


        Edward Shorter’s excellent, and very well-balanced book review is perfectly placed between the uncritical views of our field by some of our colleagues, and the singular blame that he (a usually more nuanced historian of medicine) places on the state of the field. There were likely many factors that brought us to this point.

        A former FDA official, with responsibility for approving new antidepressant drugs, Shorter took an uncritical view of DSM as the "final word" in diagnosis and in assessing efficacy. In this, he was consistent with the "usual cohort" of academic psychopharmacologists/industry consultants in the US in failing to address possible mediators and moderators of antidepressant drug efficacy. A study out of Stanford (Williams, Heifets, Blasey et al. 2018) clearly demonstrated that prior administration of a narcotic blocking drug (naltrexone) blocked the antidepressant effect of ketamine (i.e., it likely acts on the opioid receptor--and opioids were used in the early 20th century to treat depression in Germany).

        Most importantly, DSM-5 ignored cognitive deficits as the critical defining feature of schizophrenia going back to the 19th century. This may have contributed to the failure of industry to develop novel compounds; and why, when clozapine appears to have a unique profile, that we still approve antipsychotic drugs based upon the effects of these "new" drugs on the old scales related to hallucinations and delusions.

        Looking back over the past quarter century, it is possible that one of the worst things to happen to NIMH was its move to NIH -- and to some Directors with little to no experience with human psychopharmacology. Hence, the RDoC criteria -- and a failure to follow through on an initiative set 20 years ago to develop drugs that might prevent or ameliorate cognitive impairment in patients with schizophrenia. As I have looked over the program at ACNP in recent years, it is increasingly dominated by PhD basic scientists. I strongly believe that, in the absence of skilled clinical observation, functional brain imaging and animal models alone will not be able to advance the field.

        If there is a way to be helpfully critical, without empowering the anti-psychiatrists, we may yet achieve the hopes and aspirations of the pioneers in our field. They aspired for a clinically relevant and scientifically sound future for drug development in neuropsychopharmacology.



Williams NR, Heifets BD, Blasey C, Sudheimer K, Pannu J, Pankow H, Hawkins J, Birnbaum J, Lyons DM, Rodriguez CI, Schatzberg AF. Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism. Am J Psychiatry 2018;175(12):1205-14.


May 5, 2022