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Am J Psychiatry 1961;117:865-872.
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Isocarboxazid, an iproniazid analog, showed better results in the treatment of 195 patients with depressive and acute schizophrenic reactions than were seen in varying numbers of patients on 7 other antidepressants, including 223 treated with iproniazid. With a median improvement time of 8 days, isocarboxazid alone equals or exceeds ECT in speed and effectiveness, and shows no major side effects.Isocarboxazid appears to have the strongest "activation" effect of any amine oxidase inhibitor, is easily managed in maintenance usage, and can be combined with other antidepressants or tranquilizers, at least one of the latter having been used with it in every one of the 195 patients in this series. It is quite effective in both acute schizophrenic and depressed patients, and the fact that these diagnoses constitute 83% of private psychiatric hospital admissions indicates the potential wide range of application of isocarboxazid.The mood-elevating effect of isocarboxazid correlates with the rise of norepinephrine, but not with the earlier serotonin increase. The frequently seen early sedative effect of isocarboxazid, however, does accompany the rise in serotonin. This "double-action" of isocarboxazid is one of the basic reasons for the sharp difference in its clinical effects from those of amphetamine.Pharmacologically, "balanced therapy" is simply the outside reinforcement of the isocarboxazid tranquilization in agitated and disturbed patients. Although a good "balance" does not produce hyperactivation, under conditions of unusual stress the patient can be deliberately carried "higher." In the special case of extremely disturbed psychotics only partially controllable with high phenothiazine dosages, isocarboxazid can be used to provide a reinforcing reserpine-type tranquilization.Concern about possible hepatotoxicity seems unwarranted, not only because there were no significant liver function changes during this study, but because a suicidal risk with a mild chlorpromazine or endemic hepatitis showed clinical improvement and resolution of his jaundice while on isocarboxazid. The drug produces no obvious change in the ECT threshold and shows little clinical potentiation of alcohol but minimizes the "morning after." It "potentiates" phenothiazines sufficiently to improve the "tranquilization" of extremely disturbed patients.

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