Treatment Resistance: A Time-Based Approach For Early Identification in First Episode Samples

Background: Although approximately 1/3 of individuals with schizophrenia are Treatment Resistant (TR), identifying these subjects prospectively for early intervention remains challenging. The Treatment Response and Resistance in Psychosis (TRIPP; Howes et al, 2017) working group recently published consensus guidelines defining lack of response as a <20% improvement in symptoms. However, it is unclear whether these criteria are sensitive in First Episode Schizophrenia (FES). Method: Patients experiencing a first episode of psychosis referred to the Prevention and Early Intervention Program for Psychosis (PEPP) in London, Canada were followed-up with longitudinal symptom assessments. We evaluated two improvement thresholds for ‘probable TR’ classifications; <20% (as per TRIPP) and <50% to identify subjects satisfying ‘probable TR’ based on positive, negative, and total symptom domains.Results: Using the criterion of <50% total, or <20% negative symptom improvement,resulted in ‘probable TR’ rates of 37% and 33% respectively, with notable overlap between the 2criteria (77% satisfying both). Using a 20% cut-off for positive and total symptomsresulted in very low rates of ‘probable TR’. Logistic regression analyses demonstrated that poorpremorbid functioning, longer duration of untreated illness, and limited treatment response atmonths one and two were significantly associated with probable TR (<50% totalsymptom improvement).Conclusions: Our results suggest that probable TR may be identified at 6 months after FESusing a time-based approach only by including negative symptoms (either alone, with a 20%improvement threshold, or in addition to positive symptoms, with a total 50%threshold) in the definition.