Tranquillizing drugs have become widely accepted as a major form of treatment in psychiatry. However, reports in the literature on these drugs have frequently been conflicting, with a marked tendency for the results of uncontrolled studies to be much more favourable than those obtained in studies where some method of control has been adopted. Sargant (1956) has emphasized many of the social, economic, and moral implications inherent in the extravagant and indiscriminate use of tranquillizers in general and has stressed the need for the proper evaluation of their therapeutic effects. In view of this need, we undertook a controlled comparative study of the effects of two of the phenothiazine compounds, promazine (“Sparine”) and chlorpromazine (“Largactil”), in the treatment of chronic psychosis.

The discovery of chlorpromazine in the Rhône-Poulenc-Spécia laboratories in France, and the subsequent early clinical studies which were carried out in that country, for example in 1952 by Hamon et al. (5) and in 1953 by Delay and Deniker (1), eventually resulted in the enthusiastic and widespread application of this compound in the field of clinical psychiatry. Chemists and pharmacologists, in many countries, have been actively engaged during the ensuing years in the search for new compounds which might prove to be more potent therapeutic agents than chlorpromazine in the treatment of mental illness. One of the tangible manifestations of their labours is the present crop of “tranquillizers” which are being extensively used in the treatment of neurosis and psychosis. Whereas opinion may be divided with regard to the real or specific value of any one of these new drugs, few would disagree with the contention that none of them is ideal. Despite the considerable number and variety of phenothiazine derivatives and other new substances which have been developed as a result of extensive research, chlorpromazine has retained much of its original therapeutic reputation, in open competition with its rivals, down the years, and is still probably the most widely used tranquillizer today. This would seem to imply that no outstanding advance has been made since the early days of the new biochemical era in psychiatry. Valuable knowledge may have been obtained as a result of the application of scientific theory and empirical methods in this field, but in terms of effective therapeutic agents the results have been meagre, with the accent on quantity rather than quality. Nevertheless, a continued search is justifiable, and any new compound which holds forth promise must be put to a clinical test if final success is to be assured and if valuable therapeutic potential is not to be summarily dismissed or heedlessly cast aside.

Cyclizine hydrochloride (1-benzhydryl-4-methylpiperazine monohydrochloride) is a popular remedy for motion-sickness. The success which is reputed to attend the use of the drug in this condition may be a function of of two distinct effects: (a) a direct, specific inhibition of the vestibular mechanism; (b) a general, central inhibition or sedation. A consideration of the latter, rather than the former, suggested the possibility that cyclizine might prove to be of value as a potential “tranquillizer”. A controlled clinical trial was carried out in order to establish whether any tranquillizing effects might be associated with the use of the drug in a number of chronic psychotics, all of whom manifested some gross disturbance of behaviour. This paper describes the experimental method which was used; the results which were obtained; and a general comment upon the possible implications of the results in relation to other drugs used in psychiatry.

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