{
  "abstract": "Background: Esketamine is a promising therapeutic option for treatment-resistant depression (TRD). Intravenous (IV) administration is the most extensively studied parenteral route. However, subcutaneous (SC) administration may offer simpler, more scalable delivery. Multicenter real-world evidence comparing IV and SC routes of administration remains limited.\n\nObjective: To report clinical outcomes and tolerability of parenteral esketamine protocols for TRD at three Brazilian advanced-care centers.\n\nMethods: This multicenter retrospective chart review study (2023–2025) included 72 outpatients aged 18–65 years who received esketamine 2 to 3 times weekly via IV (n = 26; 6 sessions) or SC (n = 46; 12 sessions) administration. Data were analyzed in RStudio 2026.01.0 Build 392 using R 4.5.2. The primary outcome was categorical response on the Beck Depression Inventory-II (BDI-II) at the shared 6-session milestone and at each protocol-specific endpoint. Secondary outcomes included continuous changes in BDI-II and Beck Anxiety Inventory (BAI) scores in the full sample, tolerability and documented adverse events, and exploratory factor analysis of baseline symptom dimensions.\n\nResults: After six sessions, BDI-II response distribution favored the IV protocol, although the between-group difference was not statistically significant (Pearson’s chi-square = 5.661; p = 0.059; odds ratio, 3.06; 95% CI, 1.22–8.00). At the protocol-specific endpoints, categorical BDI-II response did not differ significantly between groups (Pearson’s chi-square = 1.227; p = 0.541; odds ratio, 1.44; 95% CI, 0.57–3.73). No serious adverse events or adverse-event-related discontinuations were reported; dissociation was more frequent with IV than with SC treatment (53.8% vs. 13.0%; p = 0.001), whereas nausea and mild transient blood pressure increases did not differ significantly. BDI-II factor analysis identified cognitive-affective and somatic-neurovegetative dimensions.\n\nConclusions: The IV protocol showed a more favorable BDI-II response distribution at the shared 6-session milestone, whereas SC esketamine achieved statistically comparable categorical outcomes at its 12-session protocol-specific endpoint. Route selection should consider speed of response, tolerability, dosing, operational complexity, and access. SC esketamine may be a feasible option where simplicity, tolerability, and access are priorities. Results should be interpreted with caution because of the retrospective, observational study design.",
  "abstract_shown": true,
  "affiliations": [
    "Translational Psychiatry Research Group, Federal University of Maranhão",
    "Translational Psychiatry Research Group, Universidade do Porto",
    "Translational Psychiatry Research Group, Centro Universitario Unidade de Ensino Superior Dom Bosco",
    "Translational Psychiatry Research Group, Deakin University Geelong Clinical School",
    "Translational Psychiatry Research Group, Universidade de Pernambuco"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Gilberto Sousa Alves"
    },
    {
      "affs": [
        1
      ],
      "name": "Humberto M. M Dos Santos"
    },
    {
      "affs": [
        2
      ],
      "name": "Samira D. Damasceno"
    },
    {
      "affs": [
        2
      ],
      "name": "Laura M. Maciel"
    },
    {
      "affs": [
        0
      ],
      "name": "Otavio André Farias Sousa da Silva"
    },
    {
      "affs": [
        0
      ],
      "name": "Ciro Sousa de Moura Fe"
    },
    {
      "affs": [
        0
      ],
      "name": "Jilmario G. Santana"
    },
    {
      "affs": [
        0
      ],
      "name": "Mariélia Barbosa Leal de Freitas"
    },
    {
      "affs": [
        3
      ],
      "name": "André Férrer Carvalho"
    },
    {
      "affs": [
        4
      ],
      "name": "Dennison Monteiro"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0dd6yf6ambkvx.bib",
  "cited_by": 0,
  "doi": "10.3389/fpsyt.2026.1963841",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13720280/?tool=EBI",
  "id": "0dd6yf6ambkvx",
  "issns": [
    "1664-0640"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1963841/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2736|Treatment of Major Depression"
    ]
  ],
  "openalex": "W7222434086",
  "pdf_url": "https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2026.1963841/pdf",
  "pmcid": "PMC13720280",
  "pmid": "42964351",
  "published": "2026-10-16",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/0dd6yf6ambkvx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:18Z",
      "native_id": "10.3389/fpsyt.2026.1963841",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1963841/full"
    },
    {
      "first_seen": "2026-10-31T12:21:36Z",
      "native_id": "PMC:PMC13720280",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13720280"
    },
    {
      "first_seen": "2026-11-03T12:21:11Z",
      "native_id": "PMC13720280",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fpsyt.2026.1963841"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Treatment of Major Depression",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Real-world clinical outcomes under intravenous and subcutaneous esketamine protocols for treatment-resistant depression: a multicenter, retrospective study",
  "title_text": "Real-world clinical outcomes under intravenous and subcutaneous esketamine protocols for treatment-resistant depression: a multicenter, retrospective study",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:11Z",
  "url": "https://research.draconitic.com/paper/0dd6yf6ambkvx",
  "venue": "Frontiers in Psychiatry",
  "versions": []
}