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Before They Called It Psychopharmacology* Heinz E NEUROPSYCHOPHARMACOLOGY 1993-VOL. 8, NO. 4 291 SPECIAL LECTURE Before They Called It Psychopharmacology* Heinz E. Lehmann, M.D. BEFORE THEY CALLED IT Johns Hopkins, who called the domain of psychophar­ PSYCHOPHARMACOLOGY macology "certainly very meager." Macht conducted pharmacologic experiments with opium narcotics and It is a great privilege and honor to be here today, giv­ coal tar analgesics on reaction time, tapping speed, etc., ing the second annual lecture on the history of psy­ much as Kraepelin as early as 1883 had done in Wundt's chopharmacology. My friend Frank Ayd did such an laboratory with alcohol and caffeine, calling it then Phar­ admirable job with his lecture last year, on the early macopsychologie (Macht 1920). history, that I have had a hard problem finding gaps W. Freeman, in 1931, wrote a more general paper to fill. What I have finally chosen to do is to trace for in the Journal of the American Medical Association on you some of the early history, complete with anecdotes, what he called psychochemistry, and in 1935 Thorner which preceded our modern notions of psychology and wrote the fIrst paper resembling our modern concept pharmacology and then to tell you something of my of the term with "Psychopharmacology of Sodium own experiences and findings in the psychiatric world Amytal in Catatonia." I will discuss this paper in more of the 1940s and 1950s, a world that was remarkably detail later . After a careful search of the modern litera­ different and simplistic compared to today. I also in­ ture, I came to the conclusion that official general use tend to give you a subjective "oral history" of my own of the term psychopharmacology in publications dates stumbling attempts to make some sense out of the only to 1960, following a paper by Ross and Cole enti­ vague and somewhat chaotic potpourri of ideas and tled "Psychopharmacology," when also psychophar­ pharmacologic approaches to psychiatric problems a macology appears for the fIrst time as a free-standing half century ago. item in the Cumulated Index Medicus. So, the period I will concentrate on will be pre-1960 (Freeman 1931; Thorner 1935; Ross and Cole 1960). HISTORY OF THE TERM PSYCHOPHARMACOLOGY HISTORY OF PSYCHOPHARMACOTHERAPY The term psychopharmacology was first suggested in Let us make a distinction between psychopharmaco­ theyear 1548. It was a renaissance term used by Rein­ therapy and psychopharmacology. The former is a clin­ hardLorichius in his "Psychopharmakon, hoc est Medi­ ical discipline, based mainlyon empirical observations, cina animae" (Wolman 1977). Almost 400 years later, and the latter is a scientifIc discipline that is founded in 1920, we findthe firstuse of the fullterm psychophar­ on systematic research. In the beginning, the achieve­ macology by D. Macht, a pharmacologist working at ments of the clinical psychopharmacotherapy ran ahead of those of scientifIc psychopharmacology. However, • This special lecture was presented at the 30th Annual Meeting during the last 20 years or so, academic psychophar­ of the American College of Neuropsychopharmacology in San Juan, macology and neuropsychopharmacology, with its sud­ Puerto Rico, December 10, 1991. From the Department of Psychiatry, McGill University, Montreal, den brilliant outbursts of new discoveries, sophisticated Canada. theories, and complex instrumentation seems to have Address reprint requests to: Heinz E. Lehmann, M. D., Department outrun the success of clinical psychopharmacotherapy. olPsychiatry, McGill University, Allan Memorial Institute Research Building, 1033 Pine Avenue, Montreal, PQ H3A 1A1, Canada. On Figure 1 I have tried to represent graphically Received February 26, 1992; accepted February 28, 1992. the successive milestones of modern psychopharma- @ 1993 American College of Neuropsychopharmacology Published by Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010 0893-133X/93/$6.00 292 H.E. Lehmann NEUROPSYCHOPHARMACOLOGY 1993-VOL. 8, NO.4 co therapeutics (Lehmann 1985) over the last 140 years. introduced the bromides into therapy. They were ini· The time course is charted on the horizontal axis and tially used as anticonvulsants, but later became the first the ordinate is divided into increments from one to ten, medical tranquilizers. For many years they were pre­ according to arbitrarily chosen values of the historical scribed for insomnia and anxiety. However, they were signilicance of the various discoveries. The year 1840 not very effective and also highly toxic. Interestingly, was chosen as the beginning, because it was then that their anticonvulsant action was suspected by Locock the frrstmajor breakthrough occurred with the discov­ because potassium bromide was frrstknown to reduce ery of general anesthesia. With nitrous oxide, ether, and sexual libido. Since epilepsy, during much of the 19th chloroform, pain was conquered completely for the frrst century, was believed to be caused by excessive mastur· time, at least for periods of time. In 1848, Morton suc­ bation, it seemed to follow that bromides, by reducing cessfully performed the frrstether anesthesia during a sexual impulses, should also reduce epileptic seizures. major surgical operation at the Massachusetts General One of many examples that a theory that makes no Hospital. The new medical technology of general anes­ sense may, nevertheless, stilllead to the desired results. thesia, in turn, enabled surgery to make its own rapid In 1868, chloralhydrate was introduced into medi­ progress. Further milestones in man's fIghtagainst pain cal practice as a hypnotic and it proved to be so excel· were the discovery in 1894 of cocaine by Koller and Sig­ lently suited for this purpose that today, more than a mund Freud and the introduction of the all-purpose an­ century later, it is still considered one of our best hyp­ algesic, acetylsalicylic acid, Aspirin, by Dreser in 1899. notics. Incidentally, chloralhydrate provides another Freud also was aware of the stimulating effects of historical example of the right result having been gener· cocaine on the central nervous system. He used the ated by a wrong theory. Liebreich, who introduced drug frequently himself and wrote to his fIancee how chloralhydrate as a hypnotic, had done so on the no­ the boredom at certain evening parties in Paris was tion that the drug would be metabolized in the bo dy relieved by the pleasant action of cocaine (Freud 1960). to chloroform and thus put the patient to sleep. Chern· He also wrote that cocaine lifted him almost instantane­ ically, this makes no sense, nevertheless, the drug ously out of a depression. However, it soon became works. That is, of course, all that really matters in psy· clear to him that cocaine was neither a harmless stimu­ chopharmacotherapy; why it works is a question for lant nor, as he had believed at frrst, a cure for patients the psychopharmacologists. who were addicted to morphine, but had addicting and In 1903, Fischer and von Mering synthesized dangerous properties of its own. He abandoned its use Veronal as a hypnotic barbiturate. It was, together with and from then on disliked and mistrusted psychoac­ many barbiturate derivatives, to reign supreme for more tive drugs. However, he also predicted that many of than a generation as the remedy for insomnia. Today the psychologic symptoms that at his time could only we rarely prescribe barbiturates since we are better be treated with psychoanalysis would some day be informed about their high toxicity and addictive poten· treated with hormones or other chemical substances tial. But in the frrst third of our century the many (Freud 1964). varieties of barbiturates, long-acting, intermediate, The frrstphase of psychopharmacotherapy, which short- acting, ultrashort-acting ones were, besides had concentrated on the conquest of pain, was followed chloralhydrate, the only respectable psychopharmaco­ by a phase that focused on insomnia. In 1857, Locock therapeutic agents. PSYCHOTHERAPEUTIC DRUGS 10 ANXIETY DEPRESSION 9 PSYCHOSIS MANIA 8 INHIBITION·INERTIA €NZODIAZEPINES 7 ANTIDEPRESSANTS 6 /-------...J 4 2 ANESTHESIA Figure 1. Successive milestones of modern psychopharmacotherapeutics. 1840 1850 1860 1870 1880 1890 1900 1910 1!I20 1930 1940 1950 1960 1970 ,g::o NEUROPSYCHOPHARMACOLOGY 1993-VOL. 8, NO. 4 Before They Called It Psychopharmacology 293 In 1935, the next pharmacologic attack on the psy­ nitive and perceptual symptoms as thought disorder, chologic foes of humanity was made on inhibition, in­ hallucinations, and delusions. ertiawhen Prinzmetal and Bloomberg introduced the Then in rapid succession came the antidepressants, amphetamines. These powerful stimulants have often when Klinereported on the monoamine oxidase(MAO) some euphorizing effects, and there were high hopes, inhibitors and, almost simultaneously, Kuhn on the for a little while, that a general cure for depression had tricyclics. We had some ideas how the MAO inhibitors been found. It soon became evident that the therapeu­ worked but, at frrst, no notion of the action mechanisms tic uses of amphetamines and amphetamine-like drugs of the tricyclics or, for that matter, of the antipsychotic were quite limited, although their abuses abound. action mechanism of the phenothiazines, at least not For a brief period, during and after World War II, for several years. narcoanalysis was much in vogue as a psychiatric treat­ Finally, in 1960, Randall reported on the "taming" ment modality. This technique involved the intrave­ action of chlordiazepoxide (Librium)
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