While the mechanism of action of phenothiazine and rauwolfia derivatives is not yet clearly established, most clinical workers agree that they are most effective in syndromes associated with euphoric, hostile and anxious affect. In depressive states, their therapeutic action has on the whole been rather disappointing. Phenothiazine derivatives seem at times to promote a shift from a manic to a depressive reaction in predisposed individuals, while reserpine not infrequently produces marked depressive symptoms if given over an extended period of time. A variety of treatment methods has been tried in the management of psychiatric depressions. For many years oral administration of tincture opii was the treatment of choice. (1) The amphetamines enjoyed a short-lived popularity (2) and steroid hormones were recommended for the treatment of endogenous depression (3,4,5) particularly those of the involutional type. Hematoporphyrin (6, 7) and other photosensitizing agents have also been credited with therapeutic effects, as well as dinitrile succinate (8) and nicotinic acid (9, 10). Different physical procedures have been suggested, e.g. the artificial induction of anoxia (11) and even x-ray irradiation (12) while leucotomy has still a place as a last resort procedure. None of these treatments, however, has been as reliable and prompt in action as convulsive therapy. Recently the pharmacological treatment of depressive conditions has again moved into the focus of psychiatric interest. Considerable chemotherapeutic success in the treatment of depressive states has been reported with the use of iproniazid (13, 14, 15) a drug with stimulant properties which become manifest within two to four weeks. Another drug, Imipramine (G 22355), has beeñ /CH3 CH 2-CH 2-CH2-7' HC! Structural formula of Imipramine (G 22355) claimed by Kuhn in Switzerland (16) to have given excellent results with depressed patients. In the following we are reporting our experience with this substance.°T hanks are due to Geigy Pharmaceuticals for supplying us with generous amounts of Imipramine (G22355) which enabled us to undertake this study. We wish to thank Doctors H. B. Durost, J.

In this placebo-controlled crossover study nicotinic acid, in a fixed dosage of 3000 mg. a day, produced statistically significant improvement in chronic hospitalized schizophrenic patients. We were able to reproduce the clinical observations and the results of previous workers; that is, the exacerbation of psychopathological symptoms by the combined administration of methionine and tranylcypromine. Nicotinic acid failed to prevent by prior administration or to relieve by subsequent administration, the methionine-tranylcypromine-induced exacerbation of psychopathology. This might have been due to the inadequate dosage of nicotinic acid given but the possibility of a toxic psychosis due to the metabolite, methionine sulfoximine, must be seriously considered.

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