We propose a multifaceted investigation of bipolar anergic depressive disorder, built around a six month double-blind comparison of tranylcypromine versus imipramine in treatment of this illness. Only anergic bipolar depressives will be studied because: 1) they represent 75-80% of bipolar depressed patients; 2) such a restriction assures a more homogeneous patient population; and, 3) it is a primary objective of this research to learn more about the biology of anergia, motor retardation, volitional inhibition, and hypersomnia, each of which is a hallmark of bipolar anergic depression. The clinical comparison is based on the hypothesis that tranylcypromine will be a more effective antidepressant than imipramine or other tricyclic antidepressants, because anergic patients need an arousing antidepressant. This study rests first on evidence from two uncontrolled and one placebo controlled investigation, and second on tranylcypromine's potentially superior pharmacologic characteristics. Tranylcypromine is structurally similar to amphetamine and has been demonstrated a more arousing and activating agent, a more potent rapid eye movement sleep suppressing agent, and a less anti-cholinergic agent than imipramine. In the clinical comparison we intend to use standard rating instruments, some of which have been specifically modified to detect anergic, hypersomnic symptomatology. Biological studies are intended to tap into various aspects of bipolar depression and of tranylcypromine and imipramine pharmacology. These studies consist of: 1) all-night sleep electroencephalography and multiple sleep latency tests; 2) dexamethasone suppression tests; 3) wrist-band activity determinations; 4) erythrocytic membrane sodium transport stoichiometric and kinetic measures; and, 5) platelet monoamine oxidase levels and tranylcypromine blood levels. The design of this research conforms to repeated measures one-way (tranylcypromine versus imipramine) analyses of variance (ANOVA) on each measure. Planned comparisons of means will be performed wherever the overall ANOVAs are significant. The results of this study will lead to: 1) more effective treatment of this serious illness; and, 2) fuller understanding of the psychophysiology of bipolar disorders, in particular, and mood, in general.

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