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Thomas A. Ban: Depression and the Tricyclic Antidepressants. Ronalds Federated Graphics Limited. Montreal, 1974. (74 pages).

INFORMATION ON CONTENTS: In the seventeen years following the introduction of imipramine (1957) a large number of tricylic antidepressants (TCAs) were synthesized. By 1973, at least 38 TCAs had been clinically investigated, and almost one quarter of those which had been studied, were introduced into clinical use. Yet, TCAs could control psychopathology only in one-third (or two-third including placebo responder) of depressed patients and the behavioral rating scales used in clinical investigations did not collect the necessary information to predict which patient will respond and which patient will remain refractory to these drugs. In the mid-1960s the possibility was raised that biochemical measures related to the pharmacological action of TCAs might provide pharmacologically more homogeneous sub-populations within depression, in terms of responsiveness to treatment, than psychopathology-based clinical diagnoses. The search for biological markers of depression or subpopulations of depression continued in the late 1960s and was still on the ascending part of an inverted U in the mid-1970s, at the time “Depression and the Tricyclic Antidepressants” was written. The monograph is divided into five chapters, including “Introduction” and “Concluding Remarks” with three chapters one on “Drugs,” another on depressed “Patients,” and the third, on “Depression” in between. In the “Introduction,” the story of the iminodibenzyl nucleus, the basic constituent of imipramine is outlined from the time of its synthesis in 1899 to the time of its introduction in the form of imipramine in the treatment of depression. In the chapter on “Drugs,” that follows, the pharmacological properties of TCAs with special reference to “structure-activity relationships” and their “metabolism” in humans, is discussed. In the chapter on “Patients,” questions related to efficacy, differential effects and maintenance therapy are addressed, as well as preliminary findings relevant to identification of subpopulations within depression, and prediction of treatment response to TCAs, with the employment of the Verdun Conditioning Procedure (see “Lehman and Ban’s ECDEU Progress Report 1961-1963,” in “Archives”), and the Tartu Conditioning Test Battery, are presented. In the chapter on “Depression,” the role of central cholinergic mechanisms are examined in depression; findings relevant to the catecholamine (norepinephrine) and indoleamine (serotonin) hypotheses of depression are reviewed; biochemical measures for dividing depression are entertained; and the possibility is raised for using the amplitude of the autonomic “startle response” for the identification of depression in which assumedly serotonergic mechanisms are primarily involved. Finally, in the “Concluding Remarks,” the status of pharmacotherapy of depression with TCAs in the mid-1970s is presented and augmentation strategies of therapeutic effects are discussed. Although seventeen years of research did not yield any definitive biological marker of depression or of any subpopulation of depression, expectations to find such markers were high in the mid-1970s, and the monograph concludes (in the paragraph before the last): “It is quite conceivable that in the not too distant future clinical diagnosis will be supplemented with psychophysiological, neurophysiological and biochemical correlates of the clinical state. In the same manner it is quite conceivable that in the not too distant future, in the proper selection of pharmacological treatment, behavioral, neurophysiological and biochemical laboratory data will be utilized, and dosage (of TCAs) will be based on the individual’s ability to metabolize and distribute the compound using kinetic principles.”    

AUTHOR’S STATEMENT: “Depression and the Tricyclic Antidepressnts” is an expansion of my lectures to psychiatric residents at Mc Gill University during 1973. The information covered in the monograph was also discussed in seminars with Fellows of the World Health Organization Training Program in Biological Psychiatry at McGill in the mid-1970s. The monograph was printed in 1974 with the US Library of Congress Catalog Card Number 74-76737 by Ronalds Federated Graphics Limited, Montreal, Quebec, Canada.       

Thomas A. Ban
August 8, 2013.