Two distinct patterns of treatment resistance: clinical predictors of treatment resistance in first-episode schizophrenia spectrum psychoses

Abstract

BackgroundClozapine remains the only evidence-based antipsychotic for treatment-resistant schizophrenia (TRS). The ability to predict which patients with their first onset of schizophrenia would subsequently meet criteria for treatment resistance (TR) could help to diminish the severe functional disability which may ensue if TR is not recognized and correctly treated.MethodThis is a 5-year longitudinal assessment of clinical outcomes in a cohort of 246 first-episode schizophrenia spectrum patients recruited as part of the NIHR Genetics and Psychosis (GAP) study conducted in South London from 2005 to 2010. We examined the relationship between baseline demographic and clinical measures and the emergence of TR. TR status was determined from a review of electronic case records. We assessed for associations with early-, and late-onset TR, and non-TR, and differences between those TR patients treated with clozapine and those who were not.ResultsSeventy per cent (n = 56) of TR patients, and 23% of the total study population (n = 246) were treatment resistant from illness onset. Those who met criteria for TR during the first 5 years of illness were more likely to have an early age of first contact for psychosis (<20 years) [odds ratio (OR) 2.49, 95% confidence interval (CI) 1.25–4.94] compared to those with non-TR. The relationship between an early age of first contact (<20 years) and TR was significant in patients of Black ethnicity (OR 3.71, 95% CI 1.44–9.56); and patients of male gender (OR 3.13 95% CI 1.35–7.23).ConclusionsFor the majority of the TR group, antipsychotic TR is present from illness onset, necessitating increased consideration for the earlier use of clozapine.

Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors

“…Contrary to our expectations, the study by Lally et al (2016) did not find association with negative symptoms, which could be due to the fact that they used the Positive and Negative Syndrome Scale (PANSS) negative subscale that does not incorporate all negative symptoms such as motor retardation and active social avoidance.…”

Fatores de risco associados à esquizofrenia resistente ao tratamento em primeiro episódio psicótico

“…No presente estudo, sexo, uso de substâncias e idade de início da doença não foram fatores de risco para ERT. Esses achados contrastam com o estudo de Lally et al 10 , que encontraram idade de início de doença mais precoce como preditor de ERT. Em nosso estudo, como esperado, duração de doença não tratada foi o fator mais importante para determinar ERT.…”

“…Maior intensidade de sintomas na fase aguda do primeiro episódio contribuiu como um fator de risco independente 10 , entre os pacientes em primeiro episódio com resistência ao tratamento, cerca de 70% serão resistentes logo no início do quadro, enquanto que os 30% restantes irão passar para ERT posteriormente. Identi fi car os fatores associados à resistência precoce ao tratamento poderia permiti r aos clínicos evitar o atraso na introdução da clozapina e prevenir pior prognósti co para esses pacientes.…”

“…No estudo conduzido por Agid et al 9 , 244 pacientes em PEP foram acompanhados de forma naturalísti ca, dos quais 20,5% dos pacientes ti nham ERT. Já no recente estudo de Lally et al 10 , 33,7% de todos os pacientes apresentaram resistência ao tratamento ao longo dos 5 anos de acompanhamento; no entanto, 70% desses pacientes (23,0% da população total) já apresentavam resistência ao tratamento logo no início do quadro.…”

Clozapine for Treatment-Resistant Schizophrenia: Still the Gold Standard?

“…Including non-refractory patients in trials has the effect of enhancing the perceived efficacy of the non-clozapine comparator. Clozapine has never been shown to be superior to any drug when used as the first treatment in first-episode schizophrenia [13,14] (where treatment resistance is relatively less common [15]) but is only comparatively more effective once treatment non-response has been established [16]. The sub-analyses by Samara et al [6], which excluded trials from the NMA on the grounds of dose or recruitment of treatment-intolerant subjects, did not show clozapine to be superior to comparators, but these exclusions must inevitably have weakened the statistical power of the NMA to show any differences.…”