{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T06:13:49Z","timestamp":1779257629870,"version":"3.51.4"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Postpartum depression (PPD) affects 10\u201320% of women after childbirth, with incidence reaching 30\u201350% in high-risk populations. Acute postoperative pain and sleep disturbance represent modifiable risk factors. This study evaluated whether a multimodal analgesic protocol combining dexmedetomidine and esketamine is associated with reduced PPD incidence in high-risk parturients undergoing cesarean delivery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This single-center, retrospective cohort study included 82 high-risk parturients who received intraoperative esketamine (0.25\u202fmg\/kg) followed by postoperative dexmedetomidine-esketamine patient-controlled analgesia for 48\u202fh between January 2023 and December 2024. Historical controls (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f79) from 2022 received standard sufentanil-based analgesia. The primary outcome was PPD incidence at 6\u202fweeks (Edinburgh Postnatal Depression Scale &amp;gt;10).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PPD incidence was significantly lower in the intervention group versus controls (14.6% vs. 29.1%; relative risk 0.50, 95% confidence interval 0.27\u20130.93;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.028; number needed to treat 6.9). Edinburgh Postnatal Depression Scale (EPDS) score decreased more in the intervention group (\u22122.8\u202f\u00b1\u202f3.4 vs. +0.6\u202f\u00b1\u202f4.1;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Sleep quality at postoperative day 7 was better (Pittsburgh Sleep Quality Index 6.2\u202f\u00b1\u202f2.8 vs. 8.9\u202f\u00b1\u202f3.1;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Opioid consumption decreased by 21.2% (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Exploratory biomarker assessment in a subset suggested lower interleukin-6 and higher brain-derived neurotrophic factor (both\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001), though these data were non-systematic. Psychotomimetic effects occurred in 8.5%, all transient. No significant differences in cardiovascular or respiratory adverse events were observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A multimodal analgesic protocol incorporating dexmedetomidine-esketamine multimodal analgesic protocol was associated with lower postpartum depression incidence, better sleep quality, and acceptable safety in high-risk parturients. Randomized trials are needed to establish causality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1828838","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:46:36Z","timestamp":1779255996000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of multimodal analgesic protocol with postpartum depression incidence and sleep quality in high-risk parturients"],"prefix":"10.3389","volume":"13","author":[{"given":"Hui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Shaanxi Provincial People\u2019s Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan an","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Shaanxi Provincial People\u2019s Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huajun","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Shaanxi Provincial People\u2019s Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Shaanxi Provincial People\u2019s Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Shaanxi Provincial People\u2019s Hospital","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.jpsychires.2018.08.001","article-title":"Prevalence and incidence of postpartum depression among healthy mothers: a systematic review and meta-analysis","volume":"104","author":"Shorey","year":"2018","journal-title":"J Psychiatr Res"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1745506519844044","DOI":"10.1177\/1745506519844044","article-title":"Consequences of maternal postpartum depression: a systematic review of maternal and infant outcomes","volume":"15","author":"Slomian","year":"2019","journal-title":"Womens Health"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.1016\/S0140-6736(14)61277-0","article-title":"Effects of perinatal mental disorders on the fetus and child","volume":"384","author":"Stein","year":"2014","journal-title":"Lancet"},{"key":"ref4","volume-title":"The Costs of Perinatal Mental Health Problems","author":"Bauer","year":"2014"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1146\/annurev-clinpsy-050212-185612","article-title":"Postpartum depression: current status and future directions","volume":"9","author":"O\u2019Hara","year":"2013","journal-title":"Annu Rev Clin Psychol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1089\/jwh.2013.4331","article-title":"Prevalence of sleep deficiency in early gestation and its associations with stress and depressive symptoms","volume":"22","author":"Okun","year":"2013","journal-title":"J Womens Health"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e0148343","DOI":"10.1371\/journal.pone.0148343","article-title":"The increasing trend in caesarean section rates: global, regional and national estimates: 1990\u20132014","volume":"11","author":"Betr\u00e1n","year":"2016","journal-title":"PLoS One"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"104305","DOI":"10.1016\/j.ijoa.2024.104305","article-title":"Postpartum sleep quality and physical activity profiles following elective cesarean delivery: a longitudinal prospective cohort pilot study utilizing a wearable actigraphy device","volume":"62","author":"Pandal","year":"2024","journal-title":"Int J Obstet Anesth"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"843069","DOI":"10.3389\/fncel.2022.843069","article-title":"Neuroinflammation as the underlying mechanism of postoperative cognitive dysfunction and therapeutic strategies","volume":"16","author":"Li","year":"2022","journal-title":"Front Cell Neurosci"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"515","DOI":"10.3389\/fneur.2019.00515","article-title":"The role of BDNF in the neuroimmune axis regulation of mood disorders","volume":"10","author":"Jin","year":"2019","journal-title":"Front Neurol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.2147\/NDT.S486118","article-title":"Esketamine nasal spray: rapid relief for TRD and suicide prevention-mechanisms and pharmacodynamics","volume":"20","author":"Song","year":"2024","journal-title":"Neuropsychiatr Dis Treat"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1097\/01.aoa.0001171036.71757.fb","article-title":"Intraoperative esketamine and postpartum depression among women with cesarean delivery: a randomized clinical trial obstetric anesthesia digest","volume":"45","author":"Ren","year":"2025","journal-title":"Obstet Anesth Dig"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1097\/00000542-200302000-00024","article-title":"The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects","volume":"98","author":"Nelson","year":"2003","journal-title":"Anesthesiology"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s12871-025-03606-w","article-title":"Dexmedetomidine for opioid-sparing postoperative analgesia: a systematic review and meta-analysis","volume":"26","author":"Sun","year":"2026","journal-title":"BMC Anesthesiol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s12871-023-02048-6","article-title":"Effects of dexmedetomidine on postoperative sleep quality: a systematic review and meta-analysis of randomized controlled trials","volume":"23","author":"Liu","year":"2023","journal-title":"BMC Anesthesiol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"173733","DOI":"10.1016\/j.ejphar.2020.173733","article-title":"Dexmedetomidine inhibits LPS-induced inflammatory responses through peroxisome proliferator-activated receptor gamma (PPAR\u03b3) activation following binding to \u03b12 adrenoceptors","volume":"892","author":"Fujimoto","year":"2020","journal-title":"Eur J Pharmacol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e2318611","DOI":"10.1001\/jamanetworkopen.2023.18611","article-title":"Effect of dexmedetomidine on posttraumatic stress disorder in patients undergoing emergency trauma surgery: a randomized clinical trial","volume":"6","author":"Yu","year":"2023","journal-title":"JAMA Netw Open"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1007\/s10865-018-9950-7","article-title":"Poor sleep quality increases symptoms of depression and anxiety in postpartum women","volume":"41","author":"Okun","year":"2018","journal-title":"J Behav Med"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s00737-009-0070-9","article-title":"Fragmented maternal sleep is more strongly correlated with depressive symptoms than infant temperament at three months postpartum","volume":"12","author":"Goyal","year":"2009","journal-title":"Arch Womens Ment Health"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"100422","DOI":"10.12998\/wjcc.v13.i7.100422","article-title":"Effect of esketamine on reducing postpartum pain and depression","volume":"13","author":"Lucke-Wold","year":"2025","journal-title":"World J Clin Cases"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e121347","DOI":"10.5812\/semj-121347","article-title":"Psychosocial factors of post-operative pain intensity in women undergoing cesarean section","volume":"23","author":"Samadi Marzoni","year":"2022","journal-title":"Shiraz E-Med J"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1038\/nature10130","article-title":"NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses","volume":"475","author":"Autry","year":"2011","journal-title":"Nature"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2527659","DOI":"10.1080\/0167482X.2025.2527659","article-title":"The effect of low-dose esketamine on maternal depression after cesarean delivery","volume":"46","author":"Shang","year":"2025","journal-title":"J Psychosom Obstet Gynaecol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1097\/ALN.0000000000001325","article-title":"Low-dose dexmedetomidine improves sleep quality pattern in elderly patients after noncardiac surgery in the intensive care unit: a pilot randomized controlled trial","volume":"125","author":"Wu","year":"2016","journal-title":"Anesthesiology"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1097\/ALN.0000000000000361","article-title":"Effects of dexmedetomidine on sleep quality in critically ill patients: a pilot study","volume":"121","author":"Alexopoulou","year":"2014","journal-title":"Anesthesiology"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.bja.2019.08.026","article-title":"Dexmedetomidine modulates neuroinflammation and improves outcome via alpha2-adrenergic receptor signaling after rat spinal cord injury","volume":"123","author":"Gao","year":"2019","journal-title":"Br J Anaesth"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"3465","DOI":"10.2147\/DDDT.S210511","article-title":"Dexmedetomidine attenuates neuroinflammation in LPS-stimulated BV2 microglia cells through upregulation of miR-340","volume":"13","author":"Bao","year":"2019","journal-title":"Drug Des Devel Ther"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.biopsych.2008.05.005","article-title":"Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications","volume":"64","author":"Sen","year":"2008","journal-title":"Biol Psychiatry"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1097\/AOG.0000000000004517","article-title":"Pharmacologic stepwise multimodal approach for postpartum pain management: ACOG clinical consensus No. 1","volume":"138","year":"2021","journal-title":"Obstet Gynecol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"2S","DOI":"10.1097\/01.aog.0000662880.08512.6b","article-title":"Use of multi-modal analgesia in enhanced recovery after surgery (ERAS) for cesarean sections to reduce the use of opioids [OP02-1B]","volume":"135","author":"Gwacham","year":"2020","journal-title":"Obstet Gynecol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1097\/00000542-200501000-00030","article-title":"Ketamine for perioperative pain management","volume":"102","author":"Himmelseher","year":"2005","journal-title":"Anesthesiology"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1001\/jamapsychiatry.2017.3739","article-title":"Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial","volume":"75","author":"Daly","year":"2018","journal-title":"JAMA Psychiatry"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1097\/00006199-200109000-00004","article-title":"Predictors of postpartum depression: an update","volume":"50","author":"Beck","year":"2001","journal-title":"Nurs Res"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1146\/annurev-clinpsy-101414-020426","article-title":"Biological and psychosocial predictors of postpartum depression: systematic review and call for integration","volume":"11","author":"Yim","year":"2015","journal-title":"Annu Rev Clin Psychol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1001\/jama.2015.18948","article-title":"Primary care screening for and treatment of depression in pregnant and postpartum women: evidence report and systematic review for the US preventive services task force","volume":"315","author":"O\u2019Connor","year":"2016","journal-title":"JAMA"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1828838\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:46:37Z","timestamp":1779255997000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1828838\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":35,"alternative-id":["10.3389\/fmed.2026.1828838"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1828838","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"article-number":"1828838"}}