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THE BUTYROPHENONES IN PSYCHIATRY

HEINZ E. LEHMANN AND THOMAS A. BAN, editors: THE BUTYROPHENONES IN PSYCHIATRY

Montreal: Quebec Psychopharmacological Research Association; 1964 (164 pages). Reviewed by Thomas A. Ban

INFORMATION ON CONTENTS: The Butyrophenones in Psychiatry is based on the proceedings of the First North American Symposium on the butyrophenones that was held on January 12, 1964, in L’Annociation, Quebec, Canada. The book opens with a “Preface”, in which, the editors give a brief account of the story of the first clinically introduced butyrophenones, haloperidol and triperidol, from the time of their synthesis in 1956, to the time of the symposium. By 1964, haloperidol was extensively prescribed in Europe, but in North America, its introduction and use was lagging behind.  

The book is divided into two parts, corresponding with the two sessions of the symposium: “Basic Science Session”, and “Clinical Session”. From the five papers of the “Basic Science Session” in the first, the pharmacology of butyrophenones was reviewed. It was pointed out that all phenothiazine, thioxanthene, and butyrophenone drugs with therapeutic effect in psychoses/schizophrenia are potent “cataleptogens”, antagonize psychostimulants, potentiate barbiturates and general anesthetics, and contain a three carbon chain between a tertiary nitrogen and the rest of the molecule (Aurèe Beaulnes). The similarities between these drugs are extended, in the second paper, to their effect on capillary permeability in Sprague Dawley rats (Laszlo Kato, Bela Gozsy, Marcel Lemieux, and Andre St. Jaen), and in the third, to their effect on the surface electroencephalogram in schizophrenic patients  (Herbert Mueller and Hector Warnes). In the fourth paper, the differential effects of haloperidol, chlorpromazine, chlorprothixene were presented on a battery of psychometric performance tests in a group of male schizophrenic patients (St.Jean, Arnold Lidsky, Thomas A. Ban, and Heinz E. Lehmann); and in the fifth, the differential effects  of the same drugs on spider web formation  were discussed (George Groh and Lemieux).

From the seven reports in the clinical session, in the first, carried out in 84 patients with mixed diagnoses, haloperidol, in an average daily dose of 6 mg for three weeks, was effective in twice as many patients with a diagnosis of “schizophrenia” than with a diagnosis of “neurosis” (Henri Durost, Hilary Lee and Dorothy Arthurs). In the second report, carried out in an open psychiatric setting in a general hospital, haloperidol was not tolerated because it caused severe extrapyramidal side effects (Gerald Sarwer-Foner). In the third, a comparative clinical study of haloperidol, chlorpromazine, and chlorprothixene, in 30 acute schizophrenic patients, all three drugs produced favorable changes in symptoms related to arousal and affect,  with haloperidol affecting a wider range of symptoms than the other two drugs (Heinz E. Lehmann, Ban, Valerie Matthews, and T. Garcia Rill); and in the fourth, based on two open clinical trials with a total of 28 patients, in one, haloperidol was effective in controlling agitation in the daily dose range from 7.5 mg to 15 mg, and in the other, in controlling hallucinations and delusions in the daily dose of 4.0 mg (Yves Rouleau and Bernard Jean). In the fifth report, based on a study that followed a latin-square cross-over design with haloperidol, triperidol, and floropipemide in 15 chronic psychotic patients, all three butyrophenones decreased psychotic symptomatology, with triperidol most, floropipemide least, and haloperidol in between (Warnes, Lee and Ban); and in the sixth, carried out in a total of  30 chronic schizophrenic patients, haloperidol was  more effective than fluphenazine in excited, agitated patients, whereas fluphenazine was more effective than haloperidol  in inactive and withdrawn patients (Ban and Edgar Stonehill). The final, seventh presentation of the clinical session, was an overview of the symposium. It concluded: “the butyrophenones are valuable drugs which contribute to our present (1964) therapeutic armamentarium in psychiatry” (Ban).

REVIEWER’S STATEMENT: The First North American Symposium on The Butyrophenones in Psychiatry was also the first symposium of the Quebec Psychopharmacological Research  Association (QPRA), founded in the summer of 1963, by a small number of psychiatrists in the Province of Quebec, Canada, who were interested in improving the standards of research in psychopharmacology and communication of new findings in pharmacotherapy in psychiatry. The material presented in this book, with the exception of the papers on the pharmacology of butyrophenones by Beaulnes and on the aborted clinical study with haloperidol by Sarwer-Foner  is based on studies carried out by members of QPRA from the Verdun Protestant (now Douglas) Hospital and from Hopital des Laurentides at L’Annonciation, Quebec. There was close research collaboration in psychopharmacology between these two hospitals that led to systematic clinical investigations with potential new psychotropics.  In case of the butyrophenones, this collaboration included studies on the effects of these drugs on the surface electroencephalogram and psychometric performance tests, exploratory investigations in patient with different diagnoses, and comparative studies with drugs already in use for psychoses/schizophrenia.

Thomas A. Ban

March 27, 2014