Shortly after the advent of modern psychopharmacological agents in the 1950s it was noted that their clinical use led occasionally to galactorrhoea (Gäde and Heinrich, 1955; Winnik and Tennenbaum, 1955), to menstrual disorders (Polishuk and Kulcsar, 1956), and to false positive pregnancy tests (Foxworth and Lehman, 1957; Marks and Shackcloth, 1966). The drugs were also shown to have a profound effect upon the oestrous cycle (Cranston and Segal, 1960) and breast activity (Sulman and Winnik, 1956; Sulman, 1970) of laboratory animals. Most published reports incriminated the phenothiazines, especially chlorpromazine, and the literature pertaining to this drug was reviewed in detail by De Wied (1967); but similar effects have been noted with several related psychotropic substances (Shader and Di Mascio, 1970). These side effects are generally accepted to result mainly from the action of the drugs on the hypothalamus (De Wied, 1967), but the precise mechanisms involved are not fully understood.

There is ample evidence that high doses of phenothiazines and other neuroleptics depress the pituitary-gonadal axis in experimental animals (De Wied, 1967), but the effects of these drugs on sex hormones in human subjects are still controversial (Shader and Di Mascio, 1970). Literature concerning growth hormone (GH) is even more controversial, since phenothiazines have been found to inhibit GH release in rodents (Muller et al., 1967) but to increase it in the rhesus monkey (Meyer and Knobil, 1967). In human subjects phenothiazines have been reported to depress both basal levels of GH and the response to hypoglycaemia (Sherman et al., 1971), while others have found that this response is enhanced (Schimmelbusch, Mueller and Scheps, 1971). Studies of prolactin levels are more consistent, showing raised prolactin both in experimental animals and in human subjects following administration of phenothiazines (Apostolakis et al., 1972; Hwang et al., 1971; Kleinberg et al., 1971; Sulman, 1970).

Diminished sexual activity among individuals dependent upon the opiate drugs (heroin, morphine, methadone, etc.) has been noted by Freedman (1967) and by Jurgensen (1966). A study of four populations of male patients (controls, abstainers, heroin addicts and patients maintained on methadone), suggested that although factors other than the specific drug effects may be important determinants of sexual difficulties, that the drug itself may act as a specific determinant (Cushman, 1972). This was supported by the fact that all patients claimed to have been normal before narcotic use, that heroin reduced sexual performance and desire, and that a reversal to normal sexual function rapidly occurred during enforced withdrawal. Other observations by Ding (1972), and Scher (1967) support these findings. Berzins et al. (1971), and Mott (1972) have noted that drug-dependent subjects tend to have problems of sexual identity, and Hobi (1972) suggests that psychosexual immaturity is frequently seen in drug-dependent subjects.

Lader and Wing (1965) compared amylobarbitone sodium and chlordiazepoxide as daytime sedative drugs in anxious patients. Using a formal bioassay technique they found that 65 mg. of amylobarbitone sodium was equivalent to 9 mg. of chlordiazepoxide. Essential differences in the physiological and clinical actions of the drugs were not demonstrated, and the incidence of side effects, including drowsiness, was similar in each case.

The introduction of techniques for the measurement of the serum concentrations of anticonvulsant drugs has opened up new opportunities of studying epilepsy in many of its aspects. Until the present time authors have studied variations in, and factors effecting, the metabolism of the drugs, and the relationship of serum drug concentrations to seizure control and well known side effects (see Woodbury, Penry and Schmidt, 1972). In this paper we report some preliminary observations on drug concentrations in patients with and without marked changes in their mental state.

In a previous study of old people living in the community, those with functional psychiatric disorders (usually neuroses) were found to have relatively low IQs on the Wechsler Adult Intelligence Scale (WAIS) (Britton et al., 1967). This observation required confirmation and was open to a number of interpretations.

Penrose and Smith (1966) have reviewed the literature on Down's syndrome in great detail, and this has been followed by an important recent review by Richards (1973). In Chapters 10 and 11 of Penrose and Smith's book they discuss the remarkable frequency distribution of the ages of mothers of patients, compared with that of the general population at the corresponding place and time, and they summarize the large number of studies made on this subject. The mean age of the mothers is shifted upwards by amounts which vary in different countries from about 6 to 8 years. The remarkable feature, however, is that there appear to be two bumps in the curve. These are usually (but not always) not large enough to make the curve bimodal, and J. B. S. Haldane therefore coined the term ‘bitangentiality’ for this phenomenon, which appears in most published studies and in the group of all sample cases (9,441) given by Penrose and Smith, Fig. 76. Collmann and Stoller (1962) make a complete survey of all mongol births in Victoria, Australia, from 1942 to 1957 and here there is a distinct bimodality.

It has not previously been suggested that prolactin may be involved in mental illness. Yet virtually every drug used in psychiatry either stimulates or suppresses prolactin secretion (Fluckiger, 1972). Prolactin causes renal sodium, potassium and water retention (Horrobin, 1973). It is bound to cerebral tissue and alters hypothalamic activity (Turkington and Frantz, 1972; Clemens, Gallo, Whitmoyer and Sawyer, 1971). Prolactin levels up to 100 ng./ml. potentiate the responses of smooth muscle cells to noradrenaline, while higher levels inhibit the responses: preliminary studies suggest that nerve cells behave in a similar way (Manku, Nassar and Horrobin, 1973). Emotional stress, surgery and drugs such as phenothiazines, reserpine and methyldopa can elevate human plasma prolactin levels into the 50–200 ng./ml. range (Frantz, Kleinberg and Noel, 1972; Friesen, Belanger, Guyda and Hwang, 1972).

One of the earliest and best replicated findings resulting from the experimental investigation of animal learning is that conflict can produce disordered behaviour (Pavlov, 1927). These conflicts vary in kind, ranging from a conflict, as in the circle and ellipse discrimination experiments, between responding and not responding, to a conflict between approach and avoidance as in the pairing of electric shock with food. As Kimmel (1971) points out, whether or not a conflict produces disordered behaviour is a function of the animal's previous history. An ellipse has already to be clearly associated with ‘no food’ and a circle with food for disorder to be produced by presenting a circle and ellipse which are very similar to each other. Similarly, special conditions of training can be found which enable a dog to salivate and wag his tail in response to an injury severe enough to draw blood.

Feelings that life is not worth living and thoughts of suicide are common in psychiatric patients, particularly in depressives (Beck, 1967). Very little information is available, however, regarding the occurrence of suicidal feelings in the general population. In contrast, the epidemiology of completed suicide has received extensive study (Dublin, 1963), and there have been some epidemiological studies of attempted suicide (Shneidman and Farberow, 1961; Mintz, 1964; Parkin and Stengel, 1965). However, this information cannot automatically be generalized to suicidal feelings. It has been emphasized in recent years that suicidal phenomena are diverse, and that completed suicide, suicidal attempts, and suicidal feelings should not be equated (Stengel and Cook, 1958; Neuringer, 1962).

The organization known as The Samaritans was established in 1953 in London by the Rev. Chad Varah as a suicide prevention service, but there is still an absence of data regarding the impact of this service on parasuicide (‘attempted suicide’). If it is hypothesized that the Samaritan organization does prevent parasuicide, it follows that an increase in Samaritan referrals would be associated with a decrease in parasuicide, other factors being equal. The recent B.B.C.1 programme based on the Samaritans afforded a natural experiment for testing this hypothesis.

In his review of psychotherapeutic practice today, Marks (1971) has pointed out that there is a decreasing tendency to make dogmatic assertions of universal applicability of one or other form of psychotherapy to all neurotic states. There is an increasing readiness among psychotherapists of different schools to recognize that genuine therapeutic potential may be found in a variety of techniques with widely differing underlying assumptions about the nature of neurosis. It seems increasingly probable that psychotherapists of the future will need to be conversant with many techniques and the clinical indications for each, for it is becoming unrealistic to expect all neurotic problems to be solved by one technique alone.

The sedative effects of single doses of hypnotic drugs in normals are still detectable on behavioural tests 13 hours after administration, and on the electroencephalogram (EEG) at 18 hours (Malpas et al., 1970), and similar results have been noted by other workers (Lader and Walters, 1971). Using measures of driving skill, Betts et al. (1972) have also found that normal subjects may be impaired after five doses of amylobarbitone sodium taken over the preceding 36 hours. However, the relevance of all these results to the prediction of effects in patients for whom the drugs are prescribed is uncertain, as our preliminary report indicated (Legg et al., 1973). Here we present the more detailed results of a study carried out on anxious out-patients, using behavioural and EEG measures to determine whether or not persistent effects were present following a course of 7 days treatment with hypnotic drugs.

A new benzodiazepine, bromazepam, 6 mg. three times a day was compared in a double-blind trial with medazepam, 10 mg. three times a day and with chlordiazepoxide, 10 mg. three times a day. Each drug was given for two weeks. The first 50 cases attending the out-patient department were selected. All were suffering from neurotic anxiety and were comparable to those patients for whom sedation is commonly and properly prescribed in general practice. There was no selection for either age or sex.

Despite the Department of Health and Social Security's disclaimer in paragraph 10 of H.M. 71/90, the earnings of psychiatric patients for work done in hospital were effectively limited to a maximum of £2 between the years 1958 and 1972. The progressive decline in the value of money during this period led to mounting agitation for the limit to be raised (e.g. Wansbrough, 1971, p. 29). Hospitals were notified of the decision to raise the limit in a letter (reference no. DS. 214/72) from D.H.S.S. dated August 1972, the first paragraph of which reads: ‘The National Insurance Act 1972 raises the maximum amount a person may earn whilst in receipt of National Insurance benefit from £2.00 to £4.50 a week for work carried out under medical supervision as part of his treatment as a patient of a hospital or similar institution. This takes effect from 5th October 1972.’

The results of treating psychopaths and other mentally abnormal offenders at Balderton Hospital, Nottinghamshire, and in North Wales (Tables I, II and III), have shown that there is a small intractable group who react explosively when in the company of less disturbed patients, and who are best treated in a long-term unit specially designed for their needs. The small group surveyed here are mentally abnormal offenders of dull-normal or average ability whose aggression or inadequacy, sometimes combined with schizophrenia or resulting from brain damage, makes them prone to repeated convictions for violent acts, arson, sexual offences or drunkenness.