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

Abstract

Background. We examined longitudinally the course and predictors of treatment resistance in a large cohort of firstepisode 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.

First-episode psychosis in treatment-resistant schizophrenia: a cross-sectional study of a long-term follow-up cohort

“…Demjaha et al reported the outcome of a 10-year follow-up of 434 patients in the same area (London) as in the study by Lally et al, presumably with a different cohort [8]. Among the 343 patients included in their final analysis, 74 patients (23%) were diagnosed as having TRS, 62 patients (84%) and 12 patients (16%) being diagnosed with early and late-TRS, respectively, which were quite similar to the results of Lally’s study.…”

“…Recent studies have suggested that there may be two patterns of development to TRS: an immediate transition to TRS from the time of treatment introduction (i.e., early TRS) and a later transition to TRS after a significant improvement (i.e., later TRS) [7, 8]. In addition, younger onset, higher initial negative symptoms and longer duration of untreated psychosis (DUP) have been proposed as factors predictive of transition to TRS [8].…”

“…In addition, younger onset, higher initial negative symptoms and longer duration of untreated psychosis (DUP) have been proposed as factors predictive of transition to TRS [8]. Despite these findings, however, the detailed process of development to TRS remains to be elucidated.…”

Clozapine and all‐cause mortality in treatment‐resistant schizophrenia: a historical cohort study

“…Consequently, clozapine users are likely to clinically differ from non‐clozapine users. Moreover, patients who meet the definition of treatment resistance may be biologically distinct from those with treatment‐responsive schizophrenia . In line with this, two recent studies have investigated the effect of clozapine use on mortality in TRS .…”

Can we use mice to study schizophrenia?

“…Strikingly, the enhanced striatal dopamine (figure 1) correlates with the severity of positive symptoms and predicts treatment response [48]. However, despite this strong relationship between striatal D2Rs and positive symptoms, it is important to note that 20-30% of psychotic patients do not respond to D2R blockers [49] and that not all patients with schizophrenia show enhanced precursor uptake or enhanced dopamine release.…”