{
  "abstract": "To the Editor Janik et al reported a positive trial of esketamine monotherapy for treatment-resistant depression. However, the lead-in design and functional unblinding could have biased treatment estimates. The 4-week double-blind phase was preceded by a lead-in phase of up to 7 weeks, during which time antidepressant medication was discontinued; therefore, the last 2 weeks of prerandomization were antidepressant medication free. Primary efficacy analysis included all participants randomized in the double-blind phase who met nonresponse criteria. These criteria are detailed in the article (ie, Montgomery-Åsberg Depression Rating Scale [MADRS] ≥28 during weeks 1 and 2 and at day 1 prerandomization, and ≤25% improvement in the MADRS score from week 1 to day 1 prerandomization) but not in the protocol, which only mentions that MADRS will be used during the screening phase. A total of 98 participants were excluded from the primary analysis for not meeting nonresponse criteria. Analysis of all randomized participants (eTable 2 in Supplement 2) showed a significant, albeit smaller effect as follows: a difference in least-squares mean (SE) of −5.7 (1.18) vs −6.8 (1.38) for a dose of 84 mg and −4.6 (1.23) vs −5.1 (1.42) for a dose of 56 mg.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "Ioana Cristea"
    },
    {
      "name": "Martin Plöderl"
    },
    {
      "name": "Florian Naudet"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/brnvhhcee4pb0.bib",
  "cited_by": 0,
  "doi": "10.1001/jamapsychiatry.2025.3242",
  "fulltext_url": null,
  "id": "brnvhhcee4pb0",
  "issns": [
    "2168-622X",
    "2168-6238"
  ],
  "landing_url": "https://hal.science/hal-05802459v1",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.mhep"
    ],
    [
      "hal",
      "2.sdv.mhep.psm"
    ],
    [
      "openalex",
      "2736|Treatment of Major Depression"
    ]
  ],
  "openalex": "W4415929163",
  "pdf_url": "https://hal.science/hal-05802459/document",
  "pmcid": null,
  "pmid": "41191347",
  "published": "2026-10-16",
  "publisher": "Chicago, IL : American Medical Association, [2013]-",
  "ris": "https://research.draconitic.com/paper/brnvhhcee4pb0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:58Z",
      "native_id": "hal-05802459",
      "source": "hal",
      "url": "https://hal.science/hal-05802459v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:0.sdv",
      "subfield": "general"
    },
    {
      "field": "medicine",
      "origin": "hal:2.sdv.mhep.psm",
      "subfield": "psychiatry"
    }
  ],
  "title": "Esketamine for Treatment-Resistant Depression",
  "title_text": "Esketamine for Treatment-Resistant Depression",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:58Z",
  "url": "https://research.draconitic.com/paper/brnvhhcee4pb0",
  "venue": "JAMA Psychiatry",
  "versions": []
}