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.

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.)

The detection of early or subclinical schizophrenia is a major psychiatric problem. Patients who are finally classified as schizophrenic often may not have been so considered on previous examination. In other words their true condition was not detected clinically in the first place.

Perphenazine is a phenothiazine derivative, recommended as a tranquillizer (Ayd, 1957; O'Reilly et al., 1957; Goldman, 1958; Preisig and Landman, 1958) and as an anti-emetic (Scurr and Robbie, 1958). The structural formula is 1-(2-hydroxyethyl)-4-3-(2-chloro-10-phenothiazyl)-propyl-piperazine; it has also been called Fentazin and Trilafon. Its action is similar to chlorpromazine, but it is said to be 5 or 6 times as potent, the side-effects are less severe and the potentiating effect on barbiturates is minimal. Extra-pyramidal symptoms have occurred but no serious blood-disorders or jaundice have been reported. The recommended out-patient dosage is 6 to 16 mg. daily; doses of 24 to 64 mg. daily may be used with in-patients. Autonomic side-effects such as blurred vision and dry mouth are said not to occur below 40 mg. daily, hypotension not below 150 mg. daily. The purpose of this trial was to see if perphenazine improved the symptoms of out-patients with anxiety and depression, as compared with a placebo, and also to match it with a recognized and widely used sedative, sodium amylobarbitone, in order to note any difference in effect.