Twenty outpatients suffering from chronic anxiety states completed a trial of anxiolytic drug therapy. They each received five treatments: amylobarbitone sodium, chlordiazepoxide, diazepam, medazepam, and a placebo in flexible dosage in a fully balanced design, using doubleblind procedures. They were assessed on the Hamilton rating scale for anxiety after a period of two to four weeks on each of the treatments and they completed self-ratings every three days. The selfratings were composed of at least three prime symptoms chosen by the patient himself and phrased in his own words as well as ‘loss of appetite’ and ‘insomnia’. Neither placebo nor amylobarbitone produced any substantial improvement from pre-drug levels of anxiety but all three benzodiazepines produced significant and very similar decreases in both Hamilton ratings and self-ratings. These two measures also correlated highly. The majority of the patients continued with medazepam at the end of the formal trial.

Thirty drug-free patients suffering from chronic anxiety states were compared with 30 normal controls matched for age, sex, and social class on a variety of physiological and psychological measures. The tests included the electroencephalogram, the auditory evoked response, and skin conductance recorded during a passive and an active condition and auditory reaction time, the digit symbol substitution test, and arithmetic. The patients showed increased EEG voltage, shorter latencies of the evoked response, higher skin conductance levels, higher pulse rate and less pupillary constriction, and they responded less to the increase in activation. They also showed impairment on complex psychological tests. It is concluded that pathological anxiety involves an increase in arousal irrelevant to the task and has a disorganizing rather than a facilitating effect on performance.

Twenty outpatients with chronic anxiety states were tested on a large battery of physiological and psychological tests after amylobarbitone sodium, chlordiazepoxide, diazepam, and medazepam given in flexible dosage and compared with a placebo. Each patient received all five treatments for two to four weeks under double-blind conditions, as part of a fully balanced design. The tests included the electroencephalogram, the auditory evoked response, skin conductance, the Digit Symbol Substitution Test, the Gibson Spiral Maze, and arithmetic tests, together with psychiatrist and patient ratings. Correlations within and between the different measures were computed. The benzodiazepines depressed slow wave and increased fast wave activity of the EEG, diminished the evoked response, reduced fluctuations in the skin conductance, and decreased motor speed on the Gibson Maze. Amylobarbitone had less physiological effect but impaired performance on the Gibson Maze and arithmetic tests. Significant correlations were found between the mean Hamilton and patient ratings and the physiological measures. It is concluded that physiological changes show useful correlations with clinical effects.

My choice of subject for this Memorial Lecture is one which I hope would have been approved of by the late Dr. Shorvon, who must have often applied his great therapeutic acumen to the treatment of anxious patients. I intend to present neither a compendious review of some aspect of anxiety nor a catalogue of recent research work. Rather, I shall outline some conceptual and practical problems met in investigating an emotion. Such problems have occupied medical men and also many philosophers, psychologists and theologians. I shall outline the types of anxiety, using the term loosely, and then attempt a scientific analysis ending with some speculative model-making.

In depression alteration in mood is accompanied by pronounced physical and behavioural changes. Characteristically there is a decline in appetite, weight and libido, insomnia and a disturbance of diurnal rhythm. A slowing of thought and movement to the point of severe retardation or even stupor may occur. Anxiety is often present and in agitated depression is accompanied by restless psychomotor activity. As lesions in the hypothalamus may produce disturbances in appetite, weight, libido and sleep, it has been suggested that hypothalamic dysfunction may play a part in the aetiology of those depressions in which physical symptoms predominate (Pollitt, 1965).