Phenothiazine Derivatives in the Treatment of Schizophrenia

The first use of chlorpromazine hydrochloride in mental illness was reported in France in 1952. Subsequently a variety of other phenothiazine derivatives have been introduced into psychiatry: Several controlled trials have confirmed the usefulness of chlorpromazine hydrochloride in schizophrenia. Most of these trials have involved chronic patients. Some of the other drugs have been compared with chlorpromazine hydrochloride from this point of view. Considering only evidence from double-blind trials, the following appear to be more active than chlorpromazine hydrochloride, when used in their therapeutic range of dosage (a somewhat vague proviso): The following appear to have comparable activity to chlorpromazine hydrochloride: and the following to be less effective: There is some less satisfactory evidence that acepromazine and methopromazine are also less active than chlorpromazine hydrochloride. It should be noted that these observations refer to optimal therapeutic activity and not to weight-for-weight activity. Information about the remaining ten compounds is inadequate. Complementary to the discussion of the relative clinical efficacy of these drugs is the consideration of the relative incidence of side-effects and complications. When used in their therapeutic dosage, the following drugs produce a higher incidence of Parkinsonian symptoms than does chlorpromazine hydrochloride: The following show a greater incidence of jaundice than does chlorpromazine hydrochloride: Jaundice has also occurred with promazine, but has not been reported with the others. Agranulocytosis has so far been reported with: In short, there is no indication at present that any of these drugs could usefully replace chlorpromazine hydrochloride. In those rare cases where jaundice or agranulocytosis has occurred with chlorpromazine hydrochloride, fluopromazine would seem to be indicated. There is clear evidence that chlorpromazine hydrochloride is more effective than reserpine in chronic schizophrenia, and a moderately satisfactory— though not blind—trial has suggested that it is more effective than insulin coma therapy in acute schizophrenia (Boardman, Lomas and Markowe, 1956). In the present state of our knowledge, only a clinical trial can determine whether or not a given schizophrenic patient will respond to chlorpromazine hydrochloride.