Abstract
An overview of the aims and substance of the book is presented. It discusses current thinking about depression and its treatment. It reviews the history of the development and the revolutionary impact of antidepressants (ADs) on the field. It notes that despite thousands of studies since their introduction, little has changed in ideas about the nature of the “depressive” experience. How the new drugs effect recovery remains only partially resolved. The author, involved in two multidisciplinary projects on the neurobiology and behavior of depression and its treatment during the past 30 years, observes that the disorder has not been investigated with the behavioral methods necessary to uncover its multifaceted psychological nature. Further, that the graphic articulated descriptions of the experience provided by artists afflicted over the years, have not been acknowledged. Their views and the results of phenomenologic behavioral analyses are brought together to develop a new dimensional theory of depression. It more accurately reflects the nature of the experience and its conflictual character. New, more effective drugs have not been developed since 1980. The false assumptions that currently guide research are documented and a new model proposed for further research. That model has helped to “right” the field by uncovering the timing, nature, and specificity of the actions of established drugs. As the field enters a new era of molecular biologic research, it can avoid committing the same errors as those in the ongoing neurochemical era.
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Kuhn, R. (1958). The treatment of depressive states with G22355 (imipramine hydrochloride). American Journal of Psychiatry, 115, 459–464.
Drugs that were capable of resolving the depressive disorder are viewed as having been discovered, like most drugs for the mental disorders, accidently, almost purely by chance. That conclusion derives from the fact that the effective drugs were not planned for scientifically, that is, a hypothesis proposing that a chemical or compound having a specific structure that would in turn have a positive impact on the underlying chemistry of the depressive disorder, was not guiding the experiment or actually being tested. Rather a drug that had been proposed as possibly effective for another unrelated medical disorder was being tested and turned out by chance, to be effective in treating depression. That scenario does not of course, represent the whole story or the actual course of events with antidepressants. The discovery of the drugs effective in the treatment of the psychoses and for the depressive disorders were made by clinicians whose mind sets and broad experience with patients prepared them to detect actions “unseen” by other less astute clinician observers, and led them to open the door to the novel application of the new treatment.
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The event of literally, completely “turning around” a chronic, seemingly intractable, severely depressed placebo-resistant hospitalized patient with one course of drugs over a 3 to 4 week period, would prior to the introduction of the tricyclics, occur rarely if at all. Nevertheless, in the NIMH Collaborative Study (CDS) it occurred in no less than 50% of the 104 patients treated with imipramine or amitriptyline, who were studied across the six hospitals and judged at 4 weeks to be “recovered”. The evidence for this was reported in Maas, J. W., Koslow, S., Katz, M. M., Gibbons, R., Bowden, C. L., Robins, E., & Davis, J. (1984). Pretreatment neurotransmitter metabolites and tricyclic antidepressant drug response. American Journal of Psychiatry 141:1139–1171. And the actual physical and expressive qualities of patient change are preserved through videotaped records of the baseline and post-treatment interviews during the study period.
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The last four decades have seen an intensive effort among basic investigators to uncover the links between functioning of central neurotransmitter systems and the regulation of specific behaviors. Since animal models of the depressive disorder are approximate at best, the sturdiest evidence so far generated on this linkage is that between the neurochemistry and the more elemental behaviors and emotions, such as fear and aggression. Much progress has been made in this area that is directly relevant to understanding of drug actions on the disorder (see Morilak D., & Frazer A. (2004). Antidepressant brain monoaminergic systems: a dimensional approach to understanding their effects in depression and anxiety disorders. International Journal of Neuropsychopharmacology 7:193–218) This background evidence is detailed further in a later chapter.
One view of this field during its long history in the U.S. is that the professional community appears to think only in extremes. Earlier, before the introduction of the drugs, psychiatrists and psychologists were inclined to believe that the large majority of depressions represented a classic psychological disorder, one in which the main causes were rooted in psychological development and early trauma and in which biological and somatic aspects were simply symptoms of the basic disorder. After the drugs, psychological factors were treated as minor, relatively unimportant facets of the disorder, and generally neglected in the analysis of treatment effects.
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Katz, M.M. (2013). Introduction. In: Depression and Drugs. SpringerBriefs in Psychology. Springer, Heidelberg. https://doi.org/10.1007/978-3-319-00389-4_1
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