The time course of clinical improvement was studied in 41 schizophrenic and schizoaffective acute in-patients treated for 28 days with 10, 20 or 30 mg/day of oral fluphenazine hydrochloride in a double-blind, randomised study. Significant improvement was seen in the four BPRS factors: thinking disturbance, hostile-suspiciousness, withdrawal–retardation and anxious depression. The first two of these factors were improved by day 5. Significant improvement was seen up to day 22 for three of the four factors, but without significant improvement during the last week (although scores continued to drop). The half of the sample showing greater overall improvement did not improve faster than the sample as a whole. These more improved subjects did not differ significantly from the less improved subjects in the thinking disturbance factor until day 15, suggesting that at least a two-week neuroleptic trial would be necessary to begin to differentiate more and less responsive patients. The longer-term course of improvement cannot be determined from these data. The withdrawal–retardation and anxious depression factors showed their greatest improvement later than the ‘positive’ symptom factors, suggesting that the former may improve as a result of change in the latter.

Forty-two subjects, 20 with and 22 without clinically diagnosed tardive dyskinesia (TD), were rated for TD on the scale of Simpson et al. They also performed a tongue protrusion test and had the presence of tongue movements within the buccal cavity observed. Fifty per cent of the severe or definite TD subjects as classified by rating scale were unable to maintain tongue protrusion for a minimum of 30 seconds, and 85 per cent of them had abnormal tongue movements. In 45 per cent of the possible TDs and in 9 per cent of the doubtful subjects, the movement test was also positive.

Reports have been accumulating in the literature attesting to the failure of patients, particularly out-patients, to take medication as prescribed (Stewart and Cluff, 1972; Moulding et al., 1970). The incidence of these failures, which may include anything from missing occasional doses to taking no medication at all, has been reported to range from 25–59 Per cent. In addition, it has not been possible to identify those patients who will have the highest failure rates (Blackwell, 1972). While most of the studies have involved medical patients, it is probably legitimate to assume that schizophrenic patients are at least as unreliable in taking medication as the medical patients. Thus, in one study of 125 psychiatric patients, Willcox et al. (1965) found that 48 per cent took no medication at all.

There are many reports referring to incidence of agranulocytosis in patients receiving phenothiazines. This and the potential hepatotoxic effect of this group of drugs have been the greatest drawback in their usage.