{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:53:36Z","timestamp":1793141616424,"version":"4.5.0"},"reference-count":6,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical-Scientific Fund of the Mayor of the Federal Capital Vienna","award":["21127"],"award-info":[{"award-number":["21127"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Prior evidence for the ketogenic diet (KD) interventions in treatment-resistant depression (TRD) was very limited when recruitment for the present pilot trial began on 1 November 2023. This pilot trial aimed to examine feasibility, adherence, safety, and preliminary clinical signals in patients with TRD treated with a 6-week KD intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This prospective, single-arm, open-label pilot trial was conducted in adult patients with TRD who had a baseline Montgomery-\u00c5sberg Depression Rating Scale (MADRS) score of at least 20. The intervention consisted of a 6-week KD; preexisting psychopharmacological treatment had to be stable before study entry and was not changed during the intervention. Adherence was monitored by daily fasting capillary\n                      <jats:italic>\u03b2<\/jats:italic>\n                      -hydroxybutyrate measurements. The MADRS was assessed at baseline and after 2, 4, and 6\u202fweeks in all participants. A response was defined as a\u202f\u2265\u202f50% reduction in the MADRS score from baseline; remission was defined as a MADRS score of \u226410.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 13 eligible patients were offered study participation; 5 declined, and 8 were enrolled. Four patients completed the full 6-week intervention. One patient discontinued after week 2, one patient was excluded after a revised diagnosis, and two patients discontinued because nutritional ketosis was not achieved. Nutritional ketosis was documented in all completers and was accompanied by marked symptomatic improvement in three of the four completers. Among the completers, two patients met the remission criteria at week 6, whereas one showed partial improvement and one showed no relevant antidepressant benefit despite sustained nutritional ketosis. The intervention was generally feasible, but recruitment and retention were challenging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this small prospective pilot trial, a KD was feasible in a subset of patients with TRD and was associated with improvement in depressive symptoms in three of the four completers. However, recruitment difficulties, early discontinuations, and heterogeneity of clinical responses highlight the need for larger controlled studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1870412","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:38:13Z","timestamp":1784695093000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A 6-week ketogenic diet in treatment-resistant depression: a prospective single-arm feasibility pilot trial"],"prefix":"10.3389","volume":"13","author":[{"given":"Cemre","family":"Cukaci","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Medical University of Vienna","place":["Vienna, Austria"]},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna","place":["Vienna, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Rabl","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Medical University of Vienna","place":["Vienna, Austria"]},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna","place":["Vienna, Austria"]},{"name":"Department of Psychiatry and Psychotherapeutic Medicine, University Hospital St. P\u00f6lten, Karl Landsteiner University of Health Sciences","place":["Krems an der Donau, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Frey","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Medical University of Vienna","place":["Vienna, Austria"]},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna","place":["Vienna, Austria"]},{"name":"Department of Psychiatry and Psychotherapeutic Medicine, University Hospital St. P\u00f6lten, Karl Landsteiner University of Health Sciences","place":["Krems an der Donau, Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1002\/wps.21120","article-title":"Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions","volume":"22","author":"McIntyre","year":"2023","journal-title":"World Psychiatry"},{"key":"ref2","volume-title":"Guideline on Clinical Investigation of medicinal Products in the Treatment of depression - Revision 3","year":"2025"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.21926\/rpn.2201003","article-title":"Ketogenic therapy for major depressive disorder: a review of neurobiological evidence","volume":"2","author":"Shamshtein","year":"2022","journal-title":"Recent Prog Nutr"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"951376","DOI":"10.3389\/fpsyt.2022.951376","article-title":"The ketogenic diet for refractory mental illness: a retrospective analysis of 31 inpatients","volume":"13","author":"Danan","year":"2022","journal-title":"Front Psych"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e035677","DOI":"10.1136\/bmjopen-2019-035677","article-title":"Antibiotic-induced changes in the human gut microbiota for the most commonly prescribed antibiotics in primary care in the UK: a systematic review","volume":"10","author":"Elvers","year":"2020","journal-title":"BMJ Open"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1001\/jamapsychiatry.2025.4431","article-title":"A ketogenic diet for treatment-resistant depression: a randomized clinical trial","volume":"83","author":"Gao","year":"2026","journal-title":"JAMA Psychiatry"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1870412\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:38:22Z","timestamp":1784695102000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2026.1870412\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":6,"alternative-id":["10.3389\/fnut.2026.1870412"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2026.1870412","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]},"article-number":"1870412"}}