ArticleSchizophrenia bulletin2021
Predictors of Treatment-Resistant and Clozapine-Resistant Schizophrenia: A 12-Year Follow-up Study of First-Episode Schizophrenia-Spectrum Disorders.
Article in Schizophrenia bulletin, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 5 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 5 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Brain structural abnormalities in treatment-resistant schizophrenia.Molecular psychiatry · 2026Pooled it
- A systematic review of the role of clozapine for severe borderline personality disorder.Psychopharmacology · 2023Pooled it
- A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia.CNS drugs · 2022Guideline
- Neuropsychological differences between treatment-resistant and treatment-responsive schizophrenia: a meta-analysis.Psychological medicine · 2022Pooled it
- Clozapine prescribing barriers in the management of treatment-resistant schizophrenia: A systematic review.Medicine · 2021Pooled it
- Relationships between early age at onset of psychotic symptoms and treatment resistant schizophrenia.Early intervention in psychiatry · 2022Trial
- Beyond Clozapine Failure: Precision Approach and Palliative Psychiatry in Ultra-Treatment-Resistant Schizophrenia.Journal of clinical medicine · 2026Review
- Genetic evidence for causal relationship between general cognition and treatment resistance in schizophrenia.Translational psychiatry · 2026Article
- Advancing Understanding of Treatment Response in Schizophrenia With Psychosis Using a Novel Dynamic Reward Task.Schizophrenia bulletin · 2026Article
- Premorbid school performance trajectories in patients with treatment-resistant schizophrenia prescribed clozapine in the public health system in Chile: a case-control study, 2007-2020.Psychological medicine · 2025Article
- Efficacy and tolerability of pharmacological interventions for schizophrenia non-responsive to prior treatment: a systematic review and network meta-analysis.EClinicalMedicine · 2025Article
- Comparison of Negative Symptom Network Structures Between Patients With Early and Chronic Schizophrenia: A Network and Exploratory Graph Analysis.Schizophrenia bulletin · 2025Article
- Two Long-Acting Antipsychotics in a Patient with Treatment-Resistant Schizophrenia: A Case Report.Clinics and practice · 2025Article
- Comparative effectiveness of antipsychotic treatment strategies for relapse prevention in first-episode schizophrenia in Finland: a population-based cohort study.The lancet. Psychiatry · 2025Article
- Review
- The Associative Thalamus: A Switchboard for Cortical Operations and a Promising Target for Schizophrenia.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Review
- Development of an individualized risk calculator of treatment resistance in patients with first-episode psychosis (TRipCal) using automated machine learning: a 12-year follow-up study with clozapine prescription as a proxy indicator.Translational psychiatry · 2024Article
- Article
- Predictors of functioning in treatment-resistant schizophrenia: the role of negative symptoms and neurocognition.Frontiers in psychiatry · 2024Article
- A systematic review of neuroimaging studies of clozapine-resistant schizophrenia.Schizophrenia (Heidelberg, Germany) · 2023Review
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Studies on the long-term development and early predictors of treatment-resistant schizophrenia (TRS) and clozapine-resistant TRS (CR-TRS) in patients with first-episode schizophrenia-spectrum disorders (FES) are limited and have not considered the impact of early intervention services (EIS). This study aimed to explore the development of TRS and CR-TRS among patients with FES over 12 years of follow-up. Of the 1234 patients with FES, 15% developed TRS. A total of 450 patients with schizophrenia or schizoaffective disorder were included in a nested case-control study (157 TRS and 293 non-TRS). Younger age of onset, poorer premorbid social adjustment during adulthood, longer duration of first episode, a greater number of relapses, and a higher antipsychotic dose in the first 24 months were associated with earlier TRS. CR-TRS patients, constituting 25% of TRS patients, had a poorer premorbid social adjustment in late adolescence and longer delay before clozapine initiation compared with non-CR-TRS. CR-TRS had poorer clinical and functional outcomes at 12-year follow-up. However, TRS patients on clozapine had a lower mortality rate compared with non-TRS patients. EIS did not have a significant impact on the development of TRS, but patients in the EIS group had a shorter delay of clozapine initiation. Results suggested that neurodevelopmental factors, early clinical characteristics, and requirement for higher antipsychotic dose may be associated with TRS development, highlighting multiple pathways leading to this form of illness. Specific interventions including relapse prevention and early initiation of clozapine during the early course of illness may reduce the rate of TRS and improve patient outcomes.
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Registered trials
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