PMID- 34483976 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210907 IS - 1664-0640 (Print) IS - 1664-0640 (Electronic) IS - 1664-0640 (Linking) VI - 12 DP - 2021 TI - A Clinical Rationale for Assessing the Impact of Childhood Sexual Abuse on Adjunctive Subcutaneous Esketamine for Treatment-Resistant Depression. PG - 608499 LID - 10.3389/fpsyt.2021.608499 [doi] LID - 608499 AB - Background: A history of child sexual abuse (CSA) is related to higher suicide rates and poor treatment outcomes in depressed adult patients. Twenty years after the first study investigating the effects of ketamine/esketamine on depression and suicide, there is a lack of data on the CSA effects on this emerging treatment. Here, we assess the impact of CSA on adjunctive subcutaneous (SC) esketamine for treatment-resistant depression (TRD). Methods: A directed acyclic graphic (DAG) was designed to identify clinical confounders between CSA and esketamine predictors of response. The confounders were applied in a statistical model to predict depression symptom trajectory in a sample of 67 TRD outpatients. Results: The patient sample had a relatively high prevalence rate of CSA (35.82%). Positive family history of first-degree relatives with alcohol use disorder and sex were clinical mediators of the effects of esketamine in a CSA adult population. Overall, the presence of at least one CSA event was unrelated to esketamine symptom reduction. Conclusions: Unlike responses to conventional antidepressants and psychotherapy, CSA does not appear to predict poor response to esketamine. CI - Copyright (c) 2021 Magalhaes, Sarin, Del Sant, Lucchese, Nakahira, Tuena, Puertas, Rodovalho Fava, Delfino, Surjan, Steglich, Barbosa, Abdo, Del Porto, Nemeroff, Cogo-Moreira, Lacerda and Mello. FAU - Magalhaes, Eduardo Jorge Muniz AU - Magalhaes EJM AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Sarin, Luciana Maria AU - Sarin LM AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Del Sant, Lorena Catarina AU - Del Sant LC AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Lucchese, Ana Cecilia AU - Lucchese AC AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Nakahira, Carolina AU - Nakahira C AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Tuena, Marco Aurelio AU - Tuena MA AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Puertas, Camila Brito AU - Puertas CB AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Rodovalho Fava, Victor Augusto AU - Rodovalho Fava VA AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Delfino, Rodrigo Simonini AU - Delfino RS AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. AD - Program for Care on Affective Disorders, Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Surjan, Juliana AU - Surjan J AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. AD - Program for Care on Affective Disorders, Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Steglich, Matheus Souza AU - Steglich MS AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. AD - Program for Care on Affective Disorders, Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Barbosa, Matheus Ghossain AU - Barbosa MG AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Abdo, Guilherme AU - Abdo G AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Del Porto, Jose Alberto AU - Del Porto JA AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. AD - Program for Care on Affective Disorders, Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Nemeroff, Charles B AU - Nemeroff CB AD - Department of Psychiatry and Behavioral Sciences, Institute of Early Life Adversity Research, Dell Medical School, University of Texas at Austin, Austin, TX, United States. FAU - Cogo-Moreira, Hugo AU - Cogo-Moreira H AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. AD - Department of Education, ICT and Learning, Faculty of Teacher Education and Languages, Ostfold University College, Halden, Norway. FAU - Lacerda, Acioly Luiz Tavares AU - Lacerda ALT AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. AD - Program for Care on Affective Disorders, Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. AD - Laboratory of Integrative Neuroscience, Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. AD - CNS Unit, BR Trials, Sao Paulo, Brazil. FAU - Mello, Andrea Feijo AU - Mello AF AD - Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. AD - Program for Research and Care on Violence and Post-traumatic Stress Disorder, Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil. LA - eng PT - Journal Article DEP - 20210817 PL - Switzerland TA - Front Psychiatry JT - Frontiers in psychiatry JID - 101545006 PMC - PMC8415867 OTO - NOTNLM OT - child sex abuse OT - directed acyclic graph OT - esketamine OT - sex OT - treatment-resistant depression COIS- EM reports non-financial support from Torrent Pharma and non-financial support from Hypera Pharma, outside of the submitted work. LS reports personal fees from Daiichi Sankyo Brasil, Lundbeck Brasil, Pfizer, and Janssen, and non-financial support from Takeda Brasil, Moksha8 Brasil, Torrent Pharma, outside of the submitted work. CN reports non-financial support from Eurofarma, Cristalia, and Sanofi, outside of the submitted work. Dr. Oliveira reports personal fees from Janssen outside of the submitted work. CBN research is supported by the NIMH grant MH-117293 and the National Institute on Alcohol Abuse and Alcoholism grant AA-024933. CBN has served as a consultant for Acadia Pharmaceuticals, Axsome, Compass Pathways, EMA Wellness, Epiodyne, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen Research and Development, Magnolia CNS, Magstim, Navitor Pharmaceuticals, Signant Health, Sophos, Sunovion Pharmaceuticals, Taisho Pharmaceutical, Takeda, TC MSO, and Xhale, he is a stockholder in AbbVie, Antares, BI Gen Holdings, Celgene, Corcept Therapeutics Pharmaceuticals Company, EMA Wellness, OPKO Health, Seattle Genetics, TC MSO, Trends in Pharma Development, and Xhale, he has served on scientific advisory boards for the American Foundation for Suicide Prevention, the Anxiety Disorders Association of America (ADAA), the Brain and Behavior Research Foundation, the Laureate Institute for Brain Research, Magnolia CNS, Signant Health, Skyland Trail, and Xhale, he has served on boards of directors for ADAA, Gratitude America, and Xhale Smart, he has income sources or equity of $10,000 or more from American Psychiatric Association Publishing, CME Outfitters, EMA Wellness, Intra-Cellular Therapies, Magstim, Signant Health, and Xhale, and he has patents on a method and devices for transdermal delivery of lithium (US 6,375,990B1), on a method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters by ex vivo assay (US 7,148,027B2), and on compounds, compositions, methods of synthesis, and methods of treatment (CRF receptor-binding ligand) (US 8,551,996B2). ALTL has received consulting fees from Janssen Pharmaceutical, Daiichi Sankyo Brasil, Cristalia Produtos Quimicos e Farmaceuticos, Pfizer, Mantecorp Industria Quimica e Farmaceutica, Libbs Farmaceutica, and Sanofi-Aventis over the last 24 months, and has received research fees from Janssen Pharmaceutical, Eli Lilly, H. Lundbeck A/S, Servier Laboratories, Hoffman-La Roche, and Forum Pharmaceuticals, not related to the submitted manuscript. AM has received non-financial support from Lundbeck not related to the present research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/09/07 06:00 MHDA- 2021/09/07 06:01 PMCR- 2021/08/17 CRDT- 2021/09/06 05:54 PHST- 2020/09/20 00:00 [received] PHST- 2021/07/12 00:00 [accepted] PHST- 2021/09/06 05:54 [entrez] PHST- 2021/09/07 06:00 [pubmed] PHST- 2021/09/07 06:01 [medline] PHST- 2021/08/17 00:00 [pmc-release] AID - 10.3389/fpsyt.2021.608499 [doi] PST - epublish SO - Front Psychiatry. 2021 Aug 17;12:608499. doi: 10.3389/fpsyt.2021.608499. eCollection 2021.