Clozapine Use in First-Episode Psychosis: The Singapore Early Psychosis Intervention Programme (EPIP) Perspective

Objective: Early symptomatic response is pertinent in improving outcomes in first-episode psychosis. One of the ways in which this may be achieved is by reducing inappropriate delays in clozapine initiation. This study aimed to examine clozapine prescribing practices among clinicians by establishing the prevalence of clozapine use, identifying baseline clinical and demographic factors that were associated with clozapine use, examining outcomes in clozapine users versus nonusers, and identifying inappropriate antipsychotic prescription patterns prior to clozapine initiation.

Methods: A retrospective study including all consecutive patients who had presented to the Singapore Early Psychosis Intervention Programme (EPIP) from April 2001 to June 2012 was conducted. Clinical and demographic data were extracted from the EPIP database. Incident cases of clozapine users were identified, and additional treatment histories were obtained from medical records. In addition to descriptive statistics, multivariate analysis was performed to identify factors associated with clozapine initiation.

Results: Data from 1,603 patients were available for baseline analyses. Of these, 69 patients (4.3%) had been prescribed clozapine. Having a younger age at onset, lack of employment, a lower Global Assessment of Functioning disability score, and a higher Positive and Negative Syndrome Scale total score at baseline were factors associated with clozapine use. After adjustment was made for confounders, clozapine users were found to have attained similar rates of remission and recovery as patients who did not use clozapine. Clozapine initiation was delayed by a mean of 19.3 weeks (SD = 27.1; range, 0-117). Prior to commencing clozapine, 29.4% of patients had received antipsychotic treatments above maximum limits, whereas 75% of patients were prescribed ≥ 3 different antipsychotics (median = 3; range, 2-7).

Conclusions: This study has confirmed that the prescribing of clozapine is low, delayed, and preceded by dosing of antipsychotic drugs above maximum limits. Identification of the factors found to be associated with clozapine use may encourage clinicians to consider clozapine sooner in relevant patients in hopes of achieving early symptomatic response.