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:

Blood copper had been known to be increased in pregnancy, chronic infections and neoplasms. Since the publication of Ullrich in 1942 (9), who found an increased copper level in the blood of schizophrenics, the hypercupraemia has been recognized as possibly significant and pathognomonic in this disease. Therefore during the following years a few investigators studied this aspect and also tried to prove the implications of this fact.

Changes in sympathetic nervous system responses have been noted to accompany changes in psychological states during psychiatric treatment. Funkenstein, Greenblatt and Solomon, observing the blood pressure response to epinephrine and methacholine, have reported a change in blood pressure patterns on the part of patients who benefited from electric shock treatment (1). Gellhorn has presented evidence that improvement in the psychoses is associated with heightened sympathetic reactivity (2).

In February, 1955, Howard D. Fabing described in Science (Fabing, 1955a) a clinical study using the drug azacyclonal hydrochloride (Frenquel), alpha-(4-piperidyl) benzhydrol hydrochloride. This drug is the gamma-isomer of Meratran which, although chemically similar, alpha-(2-piperidyl) benzhydrol hydrochlroide, has a rather different action. Brown and Werner (unpublished but referred to by Fabing, 1955a) reported that Frenquel prevents or diminishes central stimulation induced in the mouse by various agents, whereas Meratran has a stimulant action.

Phocomelia is a congenital malformation of the osseous system characterized by the absence or extreme smallness of the arms, forearms, thighs and legs, producing a pronounced shortening of limbs. The hands and feet, which may be fairly normal in appearance and development, seem inserted more or less directly into the shoulders or pelvis of the patient. As the micromelic appendages resemble the physical outlines of a seal's flippers, the condition is known as phocomelia.

In the last few years a number of new pharmacological agents have been introduced into psychiatry and reserpine has been one of the most controversial of these. Reports have varied from the over-enthusiastic (Noce, Williams and Rapaport, 1954), to the cautiously optimistic (Moore, 1956) and even the frankly sceptical (Cutler, Monroe and Anderson, 1957). It would be true to say, however, that all mental hospitals use reserpine now to some extent and nearly all psychiatrists are agreed that some remarkable recoveries have occurred. However, many questions remain to be answered—What kind of case improves?—What is the nature of the improvement qualitatively?—How lasting is the effect? Time alone gives the answer to some of these questions which are constantly recurring phenomena in therapeutics.

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.

The autonomic nervous system activity that has been observed to accompany grand mal epilepsy does not occur consistently with the seizures produced by electric convulsive treatment. The dilated pupils, flushing, lacrimation and gooseflesh which appear during the tonic spasm of the electrically induced seizure, and which are the outward manifestations of the autonomic storm within, are often not readily observed because of their transience; they begin to fade almost as soon as they appear and may be gone with the onset of the clonic spasm. Different patients exhibit them in different degrees and the same individual may show changes in the amount of autonomic response over a course of treatments.

The range of Phenothiazine tranquillizers continues to expand. Among more recent introductions is prochlorperazine (“Stemetil”) which incorporates a piperazine ring in the side chain.

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.

The general aim of the experiment was to discover whether, during an interview directed at discussing the patient's life, there was any significant alteration of blood-pressure, heart rate or brain waves in association with emotional content; as it turned out, changes in blood-pressure proved to be the most rewarding field for study and in consequence this aspect was accorded more attention.

The last few years have produced an extensive literature on the chemotherapy of schizophrenia (Foote, 1955; Shepherd and Watt, 1956; Wing, 1956; Kinross-Wright, 1957). Enthusiastic reports continue to appear in the American journals (Feldman, 1957; Winkelman, 1957) whereas a more cautious note is usually struck in psychiatric papers published in this country. The value of reserpine is now generally accepted (Moore and Mankin, 1957; Elkes, 1957) but it is not without dangerous side-effects (Wardell, 1957). Chlorpromazine is now used extensively and is probably a safer drug; the danger of jaundice has not proved to be a real contra-indication to the use of the drug. However, reports of deaths during treatment with chlorpromazine have been published (Stënback, 1956).

Over the past few years, there has been an increasing interest in drugs having a tranquillizing or ataractic effect on the central nervous system. Pharmaceutical houses, both here and on the other side of the Atlantic, have vied with one another to be the first to introduce the perfect tranquillizer, providing relief from tension and anxiety with no unpleasant or dangerous side-effects or tendency to addiction, and at the same time if possible to effect an improvement in the management of, if not the cure of, the psychoses.

Helping the senile patient is not easy, and treatment today is largely palliative. Recent cybernetic work (Ashby, 2), however, offered a suggestion that some alleviation might be possible. This paper describes briefly the underlying theory and how we investigated the matter clinically. (Only an outline of the theory can be given here.)