{
  "abstract": "Background and hypothesis\n\nClozapine-resistant schizophrenia (CRS) remains a major clinical challenge, with persistent symptoms and functional impairment despite adequate clozapine treatment. Real-world evidence is limited, and guidelines recommend a narrow set of augmentation strategies-aripiprazole (D2/3R partial agonist), amisulpride (D2/3R selective antagonist), and electroconvulsive therapy (ECT)-without clear guidance on selection or sequencing. This study examined augmentation choice and its association with length of stay (LOS) and symptomatic outcomes.Study design\n\nWe conducted a retrospective cohort study using BC Psychosis Program electronic records (2012-2025). Symptom severity and functioning scores (PANSS, CGI-S, GAPS, SOFAS) were extracted at admission and discharge. Multivariable Cox models assessed LOS for index and discharge augmentation strategies. ANCOVA compared symptom change across discharge strategies. A machine-learning model examined predictors of ECT versus pharmacological augmentation at discharge.Study results\n\nEighty-eight admissions were included. In adjusted index models, D2/3R selective antagonism was associated with shorter LOS than ECT (HR 2.50, 95% CI 1.35-4.62); partial agonism was not (HR 1.41, 95% CI 0.75-2.63). Partial agonist augmentation had the highest inefficacy-related switching. By discharge strategy, ECT was associated with greater reduction in positive symptoms than selective antagonism (MD -3.20, 95% CI -5.65 to -0.75) and partial agonism (MD -3.87, 95% CI -6.57 to -1.16). Greater impairment in psychosis and functioning on admission predicted ECT at discharge (AUC 0.74; balanced accuracy 0.72).Conclusions\n\nD2/3R selective antagonism was the most resource-efficient strategy, while ECT produced greater improvement in positive symptoms. Incorporating baseline psychosis severity and functioning into measurement-based care may support more informed augmentation selection.",
  "abstract_shown": true,
  "affiliations": [
    "Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, V6T1Z3, Canada.",
    "Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, V6T2A1, Canada.",
    "BC Psychosis Program, Vancouver, British Columbia, V6T2A1, Canada.",
    "Machine Learning Engineer based in San Francisco, San Francisco, CA, United States.",
    "Non-Invasive Neurostimulation Therapies Laboratory, Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, V6T2A1, Canada.",
    "School of Biomedical Engineering, Faculty of Applied Science | Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, V6T1Z3, Canada."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Kaitlyn Baldwin"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "William G Honer"
    },
    {
      "affs": [
        3
      ],
      "name": "Reza Shahbazi"
    },
    {
      "affs": [
        1
      ],
      "name": "Diane Fredrikson"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Randall F White"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Fidel Villa-Rodriguez",
      "orcid": "0000-0002-8273-8820"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Reza Rafizadeh",
      "orcid": "0000-0002-4163-8241"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3k9m5v3x1a1bc.bib",
  "cited_by": 0,
  "doi": "10.1093/schbul/sbag187",
  "fulltext_url": "https://europepmc.org/articles/PMC13716498",
  "id": "3k9m5v3x1a1bc",
  "issns": [
    "1787-9965",
    "1745-1701",
    "0586-7614"
  ],
  "landing_url": "https://europepmc.org/article/MED/42951688",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "AcademicSubjects/MED00810"
    ],
    [
      "heading",
      "Regular Article"
    ],
    [
      "openalex",
      "2738|Schizophrenia research and treatment"
    ]
  ],
  "openalex": "W7224298858",
  "pdf_url": "https://europepmc.org/articles/PMC13716498?pdf=render",
  "pmcid": "PMC13716498",
  "pmid": "42951688",
  "published": "2026-10-01",
  "publisher": "Oxford University Press",
  "ris": "https://research.draconitic.com/paper/3k9m5v3x1a1bc.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:35Z",
      "native_id": "MED:42951688",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42951688"
    },
    {
      "first_seen": "2026-11-01T12:23:26Z",
      "native_id": "PMC13716498",
      "source": "pmc",
      "url": "https://doi.org/10.1093/schbul/sbag187"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Schizophrenia research and treatment",
      "subfield": "psychiatry"
    }
  ],
  "title": "Clozapine Augmentation Strategies and Clinical Predictors of Prolonged Tertiary Hospitalization in Clozapine-Resistant Schizophrenia: a Retrospective Cohort Study.",
  "title_text": "Clozapine Augmentation Strategies and Clinical Predictors of Prolonged Tertiary Hospitalization in Clozapine-Resistant Schizophrenia: a Retrospective Cohort Study.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:23:26Z",
  "url": "https://research.draconitic.com/paper/3k9m5v3x1a1bc",
  "venue": "Schizophrenia bulletin",
  "versions": []
}