Predictors of psychosis breakthrough during 24 months of long-acting antipsychotic maintenance treatment in first episode schizophrenia

Abstract

BackgroundSome patients develop breakthrough psychotic symptoms on antipsychotic maintenance medication (BAMM), despite receiving therapeutic antipsychotic doses to which they previously responded. MethodsWe examined the occurrence of BAMM in previously minimally treated first-episode patients with schizophrenia-spectrum disorders who were treated according to a standard protocol with a long-acting injectable antipsychotic and regularly assessed over 24 months. ResultsOf 99 patients (age = 24.1 ± 6.5 years, male = 73.7%) who received treatment for ≥6 months (mean follow-up = 20.0 ± 6.5 months) and had responded well to treatment, 21 (21.2%) developed BAMM using operationally defined criteria, after a mean of 17.4 ± 6.1 months. Baseline risk factors for BAMM included lower baseline Positive and Negative Syndrome Scale positive symptoms, poorer quality of life in social relationships and higher blood - high-density lipoprotein-cholesterol. Regarding intra-treatment-factors, BAMM was independently predicted by an increase in low-density lipoprotein-cholesterol and current cannabis use. We did not find a relationship between BAMM and cumulative antipsychotic exposure or dose escalation. While symptoms of the BAMM episode were less severe than during the first episode, the post-BAMM treatment response was poorer than that for the first psychotic episode, suggesting a relationship between BAMM and emergent treatment refractoriness. ConclusionsAbout one in five patients with first-episode schizophrenia developed BAMM during the first two years of treatment, despite assured antipsychotic LAI treatment, indicating that this phenomenon is not restricted to the chronic stages of illness. The role of cannabis use and a possible link between BAMM and blood lipids should be further explored.