{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:42:54Z","timestamp":1760244174387,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002803","name":"Italian Cariplo Foundation","doi-asserted-by":"publisher","award":["2019-3396"],"award-info":[{"award-number":["2019-3396"]}],"id":[{"id":"10.13039\/501100002803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>The advent of intra-nasal esketamine (ESK), one of the first so called fast-acting antidepressant, promises to revolutionize the management of treatment resistant depression (TRD). This NMDA receptor antagonist has proven to be rapidly effective in the short- and medium-term course of the illness, revealing its potential in targeting response in TRD. Although many TRD ESK responders are able to achieve remission, a considerable portion of them undergo a metamorphosis of their depression into different clinical presentations, characterized by instable responses and high recurrence rates that can be considered closer to the concept of Difficult to Treat Depression (DTD) than to TRD. The management of these DTD patients usually requires a further complex multidisciplinary approach and can benefit from the valuable contribution of new personalized medicine tools such as therapeutic drug monitoring and pharmacogenetics. Despite this, these patients usually come with long and complex previous treatments history and, often, advanced and sophisticated ongoing pharmacological schemes that can make the finding of new alternative options to face the current recurrences extremely challenging. In this paper, we describe two DTD patients\u2014already receiving intranasal ESK but showing an instable course\u2014who were clinically stabilized by the association with minocycline, a semisynthetic second-generation tetracycline with known and promising antidepressant properties.<\/jats:p>","DOI":"10.3390\/jpm12091524","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T02:06:50Z","timestamp":1663553210000},"page":"1524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Possible Use of Minocycline in Adjunction to Intranasal Esketamine for the Management of Difficult to Treat Depression following Extensive Pharmacogenomic Testing: Two Case Reports"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1436-1961","authenticated-orcid":false,"given":"Matteo","family":"Marcatili","sequence":"first","affiliation":[{"name":"Psychiatric Department, San Gerardo Hospital, ASST Monza, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Borgonovo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noemi","family":"Cimminiello","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ranieri Domenico","family":"Cornaggia","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Casati","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristian","family":"Pellicioli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Maggioni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1249-4397","authenticated-orcid":false,"given":"Federico","family":"Motta","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Redaelli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Ledda","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico Emanuele","family":"Pozzi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy"},{"name":"Department of Neurology, San Gerardo Hospital, ASST Monza, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela","family":"Krivosova","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy"},{"name":"Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, 03601 Martin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Pagano","sequence":"additional","affiliation":[{"name":"National Research Council Neuroscience Institute, 20100 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Nava","sequence":"additional","affiliation":[{"name":"Psychiatric Department, San Gerardo Hospital, ASST Monza, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4984-9908","authenticated-orcid":false,"given":"Fabrizia","family":"Colmegna","sequence":"additional","affiliation":[{"name":"Psychiatric Department, San Gerardo Hospital, ASST Monza, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2328-3862","authenticated-orcid":false,"given":"Antonios","family":"Dakanalis","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8493-0779","authenticated-orcid":false,"given":"Alice","family":"Caldiroli","sequence":"additional","affiliation":[{"name":"Psychiatric Department, San Gerardo Hospital, ASST Monza, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Capuzzi","sequence":"additional","affiliation":[{"name":"Psychiatric Department, San Gerardo Hospital, ASST Monza, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Benatti","sequence":"additional","affiliation":[{"name":"Psychiatry Unit, Department of Biomedical and Clinical Sciences \u201cLuigi Sacco\u201d, University of Milan, 20100 Milan, Italy"},{"name":"CRC \u201cAldo Ravelli\u201d for Neurotechnology and Experimental Brain Therapeutics, University of Milan, 20100 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernardo","family":"Dell\u2019Osso","sequence":"additional","affiliation":[{"name":"Psychiatry Unit, Department of Biomedical and Clinical Sciences \u201cLuigi Sacco\u201d, University of Milan, 20100 Milan, Italy"},{"name":"CRC \u201cAldo Ravelli\u201d for Neurotechnology and Experimental Brain Therapeutics, University of Milan, 20100 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Bertola","sequence":"additional","affiliation":[{"name":"Cytogenetics and Medical Genetics Unit, Centre for Disorders of Iron Metabolism, San Gerardo Hospital, ASST Monza, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoletta","family":"Villa","sequence":"additional","affiliation":[{"name":"Cytogenetics and Medical Genetics Unit, Centre for Disorders of Iron Metabolism, San Gerardo Hospital, ASST Monza, 20900 Monza, 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Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0662-9523","authenticated-orcid":false,"given":"Carlo","family":"Sala","sequence":"additional","affiliation":[{"name":"National Research Council Neuroscience Institute, 20100 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2050-9846","authenticated-orcid":false,"given":"Luciano","family":"Conti","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cell Biology, Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38122 Trento, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Clerici","sequence":"additional","affiliation":[{"name":"Psychiatric Department, San Gerardo Hospital, ASST Monza, 20900 Monza, Italy"},{"name":"Department of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6603","DOI":"10.4088\/JCP.19r12889","article-title":"Efficacy of esketamine augmentation in major depressive disorder: A meta-analysis","volume":"81","author":"Papakostas","year":"2020","journal-title":"J. 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