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

TLDR

We examined longitudinally the course and predictors of treatment resistance in a large cohort of first‑episode psychosis patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is present at illness onset and differentially associated with clinical and demographic factors. The study followed 323 first‑episode psychosis patients from first contact to a 10‑year follow‑up, collecting clinical data on symptom severity, medication, and adherence to assess treatment resistance. Twenty‑three percent of patients were treatment resistant, 84% of whom were resistant from illness onset, and schizophrenia diagnosis, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted early resistance, underscoring the need for early clozapine consideration.

Abstract

Background We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: ( a ) present at illness onset; and ( b ) differentially associated with clinical and demographic factors. Method The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance. Results From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset. Conclusions The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.