33. Clinical Predictors of 2 Types of Treatment Resistance in Patients With Psychosis

Abstract

Background: The research has consistently demonstrated that around 30% of patients with schizophrenia will develop resistance to the available treatments during the course of their illness. It has now been shown that 70% of these patients are actually treatment resistant from the start of the illness (i.e., “Early-treatment resistance” (E-TR) group); whereas 30% gradually transition to treatment resistance having initially responded to treatment at the start of the illness (i.e., “Late-treatment resistance” (L-TR) group). The identifcation of the two types of treatment resistance may imply that there may be 2 distinct mechanisms responsible for onset of treatment resistance in patients with schizophrenia. However, it is not clear what proportion of patients with frst-episode psychosis (FEP) will develop these types of treatment resistance and whether there are specifc risk predictors that can be used to measure risk for these types of treatment resistance after onset of FEP. Methods: This is a 5-year longitudinal study of a cohort of 352 FEP patients recruited as part of the NIHR Genetics and Psychosis (GAP) study in South London from 2005 to 2010. At baseline patients' cognitive ability was measured with Wechsler Adult Intelligence Scale (WAIS)-3rd Ed., different memory functions were measured with Wechsler Memory Scale (WMS)-3rd Ed., and psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS). Using logistic regression analyses, we examined the relationship between baseline cognitive and clinical measures and the emergence of E-TR and L-TR. These analyses were adjusted for as age at frst contact with mental health services, living arrangements and substance use at 5 years of follow up. Area under the receiver operating characteristic curve (AUC) was utilized to assess discrimination ability of the models. Results: Of all, n = 352 FEP patients, 26.7% (n = 94) met criteria for TR by the end of the 5-year follow-up period after frst contact with mental health services; of these, n = 59 (14.8% of n = 352, and 62.8% of n = 94 TR patients) were E-TR patients, and n = 34 (9.5% of n = 352, and 26.2% of n = 94 TR patients). L-TR was signifcantly associated with blunted affect (OR = 1.56, 95% CI = 1.04-2.25, AUC = 0.81) and motor retardation (OR = 1.69, 95% CI = 1.00-2.85, AUC = 0.80). The E-TR was sig-nifcantly associated with cognitive traits, such as delayed memory recall (OR = 1.30, 95%CI = 1.03-1.65, AUC = 0.81), delayed thematic memory score (OR = 1.23, 95%CI = 1.00-1.52, AUC = 0.81) and memory recognition score (OR = 1.29, 95%CI = 1.04-1.61, AUC = 0.83). Conclusion: There may be 2 distinct mechanisms responsible for onset of treatment resistance in FEP patients. If these results are replicated, they may lay a foundation for a risk calculator. This in turn may provide a rationale for clini-cians to pursue other more appropriate interventions based on an individual level of risk implied by an individual's profle across a set of risk factors.