With the advent of effective physical therapies, psychiatrists have become increasingly interested in the problems posed by clinical trials. Professor Bradford Hill, in the Preface to the Sixth Edition of his Principles of Medical Statistics (1) noted that “… passage of time has … brought clinical trials into prominence and fashion …”. More recently Professor Pickering has described the clinical trial as “the most important new method introduced into clinical science in recent years” (2). Some interesting differences between controlled and uncontrolled trials are well brought out in the paper by Foulds (3) in which he found that therapeutic success was claimed in 85 per cent. of studies not using control groups. Among those studies using control groups, however, only 25 per cent. obtained a positive result. He concluded that “claims for the success of a treatment are closely associated with absence of the means whereby these claims can be scientifically substantiated”.

A patient in a state of stupor presents one of the most remarkable phenomena seen in medicine. The term “stupor” itself is in widespread use in general medicine and usually refers to partial or near coma. Its precise use in psychiatric practice implies a condition of immobility and muteness without loss of consciousness or organic paralysis. The term “akinetic mutism” is sometimes used to describe such states, particularly by neurologists. The actual clinical appearance or syndrome is too well known to warrant a detailed description. Essentially, for the purposes of this paper, it is equated with akinesis and mutism.

Stoll, in 1947, reported on the effects of LSD-25, an ergot alkaloid which can produce striking mental changes in normal persons, when given in microgram quantities. Since this original report, many papers and provocative ideas on the subject have appeared.

In a recent paper Walton (3) has described the diagnostic and predictive accuracy of the Modified Word Learning Test (Walton and Black (4)) in relation to psychiatric disorders of the senium. Walton assessed the predictive value of the test in terms of changes in diagnosis over a two-year period. However, as Payne (2) has pointed out, a diagnosis, as such, can only be regarded as a kind of label, of interest not in its own right, but because of its implications. These, Payne has argued, are commonly fourfold, being related to (a) aetiology, (b) description, (c) the effects of treatment and (d) prognosis.

There is a considerable literature dealing with the relation of anxiety to conditioning performance in human subjects. When compared with normal subjects, those with marked anxiety have been observed to show more rapid conditioning and slower extinction of certain responses. Typical observations have been those of Taylor (17) concerning conditioned eyelid responses, and of Welch (20), and Bitterman and Holtzman (3), concerning the galvanic skin response. In contrast, Bindra et al. (2) found no difference in the conditioning of salivary responses between anxious and non-anxious subjects.

Recent work, such as that of Moore and Martin (1957), has shown that reserpine is of value in the treatment of the chronic schizophrenic patient. Attention has however been drawn to the incidence of side-effects in this form of treatment. These side-effects have limited the application of the drug and have also led to the search for a related substance, of similar clinical effect but without the troublesome toxic effects. This present trial is of a substance, deserpidine (Harmonyl, Abbott Laboratories), which it was thought would fulfil these requirements. The isolation of this alkaloid was first reported in 1955 by Stoll and Hofman, and it has subsequently been identified as 11-desmethoxy-reserpine (Harrisson, 1955) which can be represented thus:

Phillipson's Object Relations Technique (Phillipson, 1955) is roughly described as possessing features to be found in the T.A.T. and Rorschach methods. It consists of 13 cards, including a blank card. The design of the test and the order of card presentation are depicted in Table I.

Drug treatment of depressive states has hitherto been somewhat disappointing but recent reports by Kuhn (1957, 1958), Kielholz and Battegay (1958) from Switzerland, and Azimo and Vispo (1958) from Canada have claimed that imipramine hydrochloride (Tofranil) has “thymoleptic” qualities and is of specific therapeutic value in states of endogenous depression and allied affective disorders.