Treatment strategies and their comparative effectiveness in relapse prevention after the first relapse in persons with first-episode schizophrenia

Background: It is not known which are the best pharmacological treatment practices for relapse prevention in patients with first-episode schizophrenia.

Objectives: The aim of this study was to assess different treatment strategies utilized before and after the first relapse, and their associations with the risk of subsequent relapse in persons with first-episode schizophrenia.

Methods: Cohort of persons with first-episode schizophrenia was identified from nationwide register of inpatient care in Finland. For this study, we included patients who experienced their first psychosis relapse (N=3000), with at least 30 days in outpatient care required between relapses. Treatment strategies were assessed during 30 days before admission and 30 days after discharge of the first relapse based on treatment episodes modelled with PRE2DUP method and categorized as long-acting injectable (LAI), clozapine, other non-clozapine oral antipsychotic (OAP) monotherapy, and OAP polytherapy vs. non-use of antipsychotics. The risk of the second relapse was modelled with Cox regression models, with treatment strategy changes as an exposure, by adjusting for age, sex and duration of hospitalization at the first relapse.

Results: Mean age of the cohort experiencing their first psychosis relapse was 30.0 (SD 7.6) and 1069 (35.6%) of patients were women. Before the first relapse, most persons were without antipsychotics (45.5%), or using OAP monotherapy (32.4%). After the first relapse, the proportion of non-users decreased to 23.5% whereas LAI use increased from 3.9% to 10.2% and clozapine use from 10.4% to 18.7%. Most common changes in treatment strategy were from non-use to OAP monotherapy (27.7% of prior non-users) and from OAP polytherapy to monotherapy (17.2% of prior polytherapy users) whereas 86.3% of LAI users and 83.0% of clozapine users continued their prior use. Of those who used OAP monotherapy before and after relapse (N=611), only 15.5% switched medication.
After the first relapse, 71.7% progressed to the second relapse. In general, treatment strategies associated with the lowest risk of the second relapse included switch to clozapine or LAI. When compared to continuing with the same treatment strategy which was used before the first relapse, switch to clozapine was associated with significantly decreased risk of the second relapse for prior non-users of antipsychotics (adjusted Hazard Ratio, aHR, 0.52, 0.41-0.65), for prior OAP monotherapy users (0.66, 0.49-0.89), and for prior OAP polytherapy users (0.30, 0.16-0.56).

Conclusions: Our results show that when a patient with first-episode schizophrenia experiences psychosis relapse despite of the use of non-clozapine oral antipsychotic, clozapine should be started.