RESEARCH into the nature of depression and its treatment by drugs is hobbled by the fact that depressions do not constitute a single homogeneous entity. The term "depression" is employed to refer to a symptom, a syndrome, or a diagnostic entity.1 It has been unclear whether so-called antidepressant drugs are to be regarded as specifically effective for treatment of the symptom, syndrome, or diagnostic entity. Our research has led us to the conclusion that it is important to evaluate the potential usefulness of drug treatments in distinct syndromes of depression.
In our series of studies, we began by comparing the therapeutic efficacy of antidepressant drugs among heterogeneous groups of patients whose presenting symptom was predominantly depression of mood. Although it was possible to demonstrate a significant average difference in therapeutic response between a tricyclic antidepressant, imipramine, and placebo, the difference was not striking.2 A subsequent study, which
Hollister LE, Overall JE, Shelton J, Pennington V, Kimbell I, Johnson M. Drug Therapy of Depression: Amitriptyline, Perphenazine, and Their Combination in Different Syndromes. Arch Gen Psychiatry. 1967;17(4):486–493. doi:10.1001/archpsyc.1967.01730280102012
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