Randomized Controlled Trial of Clozapine and CBT for First-Episode Psychosis with Enduring Positive Symptoms: A Pilot Study

Here we report the results of a pilot study investigating the relative and combined effects of a 12 week course of clozapine and CBT in first-episode psychosis patients with prominent ongoing positive symptoms following their initial treatment. Patients from our early psychosis service who met the inclusion criteria (𝑛=48) were randomized to one of four treatment groups: clozapine, clozapine plus CBT, thioridazine, or thioridazine plus CBT. The degree of psychopathology and functionality of all participants was measured at baseline then again at 6, 12 and 24 weeks, and the treatment outcomes for each group determined by statistical analysis. A substantial proportion (52%) of those treated with clozapine achieved symptomatic remission, as compared to 35% of those who were treated with thioridazine. Overall, those who received clozapine responded more rapidly to treatment than those receiving the alternative treatments. Interestingly, during the early treatment phase CBT appeared to reduce the intensity of both positive and negative symptoms and thus the time taken to respond to treatment, as well having as a stabilizing effect over time.