{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T17:28:53Z","timestamp":1784827733469,"version":"3.55.0"},"reference-count":41,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T00:00:00Z","timestamp":1575417600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:p>Objective:To review the pharmacology, pharmacokinetics, efficacy, safety, use requirements, and place in therapy of esketamine for treatment-resistant depression (TRD). Data Sources: A comprehensive PubMed search (1966 to October 2019) was conducted using the search terms depression, treatment-resistant, suicide, intranasal, esketamine, and JNJ-54135419. Additional data were obtained from references of identified articles, governmental sources, manufacturer product labeling, and Clinicaltrials.gov . Study Selection and Data Extraction: All English-language trials evaluating intranasal esketamine for TRD were included and discussed. Data Synthesis: Intranasal esketamine was approved by the US Food and Drug Administration, in conjunction with an oral antidepressant, for treating TRD in adults. Two short-term trials (TRANSFORM-1 and -2) found statistically significant reduction in the Montgomery-Asberg Depression Rating Scale score at day 28 for the fixed 56-mg dose (\u22124.1; 95% CI = \u22127.69 to \u22120.49; P = 0.027 [exploratory]) and flexible-dosed arms (\u22124.0; 95% CI = \u22127.31 to \u22120.64; P = 0.02), though the fixed-dose 84-mg arm (\u22123.2; 95% CI = \u22126.88 to 0.45; P = 0.088) of TRANSFORM-1 and TRANSFORM-3 did not (\u22123.6; 95% CI = \u22127.2 to 0.07; P = 0.059). Two long-term trials (SUSTAIN-1 and -2) suggested maintenance of response with continued use. Esketamine\u2019s adverse effects include dizziness, dysgeusia, somnolence, dissociation, suicidal thoughts and behaviors, and increased heart rate and blood pressure. Relevance to Patient Care and Clinical Practice: Although providing a novel antidepressant mechanism and formulation for TRD, esketamine\u2019s role in treatment will likely be limited by cost, administration, and diversion concerns. Conclusion: Intranasal esketamine significantly reduced depression symptoms in TRD, though with tolerability issues.<\/jats:p>","DOI":"10.1177\/1060028019892644","type":"journal-article","created":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T03:49:47Z","timestamp":1575431387000},"page":"567-576","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":73,"title":["Esketamine: A Novel Option for Treatment-Resistant Depression"],"prefix":"10.1177","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6505-8719","authenticated-orcid":false,"given":"Kevin M.","family":"Bozymski","sequence":"first","affiliation":[{"name":"Medical College of Wisconsin School of Pharmacy, Milwaukee, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0732-0093","authenticated-orcid":false,"given":"Ericka L.","family":"Crouse","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika N.","family":"Titus-Lay","sequence":"additional","affiliation":[{"name":"California Northstate University College of Pharmacy, Elk Grove, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A.","family":"Ott","sequence":"additional","affiliation":[{"name":"Purdue University College of Pharmacy, West Lafayette, IN, USA"},{"name":"Eskenazi Health, Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8264-1180","authenticated-orcid":false,"given":"Jill L.","family":"Nofziger","sequence":"additional","affiliation":[{"name":"Nationwide Children\u2019s Hospital, Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia K.","family":"Kirkwood","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,12,4]]},"reference":[{"key":"bibr1-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2017.08.019"},{"key":"bibr2-1060028019892644","unstructured":"World Health Organization. Depression and other common mental disorders: global health estimates. https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/254610\/WHO-MSD-MER-2017.2-eng.pdf. Accessed November 5, 2019."},{"key":"bibr3-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.2006.163.11.1905"},{"key":"bibr4-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2013.10.043"},{"key":"bibr5-1060028019892644","unstructured":"Gelenberg AJ, Freeman MP, Markowitz JC, et al. Practice guideline for the treatment of patients with major depressive disorder. Third edition. 2010. https:\/\/psychiatryonline.org\/pb\/assets\/raw\/sitewide\/practice_guidelines\/guidelines\/mdd.pdf. Accessed November 5, 2019."},{"key":"bibr6-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1177\/0706743716659417"},{"key":"bibr7-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.2018.196"},{"key":"bibr8-1060028019892644","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.19f12820"},{"key":"bibr9-1060028019892644","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.17f11738"},{"key":"bibr10-1060028019892644","doi-asserted-by":"publisher","DOI":"10.9740\/mhc.2017.01.016"},{"key":"bibr11-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1016\/s0165-0327(99)00162-7"},{"key":"bibr12-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2016.16010037"},{"key":"bibr13-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2012.06.022"},{"key":"bibr14-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.18070834"},{"key":"bibr15-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2017.17040472"},{"key":"bibr16-1060028019892644","unstructured":"US Food and Drug Administration. FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor\u2019s office or clinic. https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-new-nasal-spray-medication-treatment-resistant-depression-available-only-certified. Accessed November 5, 2019."},{"key":"bibr17-1060028019892644","unstructured":"Spravato\u2122 [package insert]. Titusville, NJ: Janssen Pharmaceuticals Inc; 2019."},{"key":"bibr18-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1097\/HRP.0000000000000183"},{"key":"bibr19-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1177\/2045125316631267"},{"key":"bibr20-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1002\/bdd.336"},{"key":"bibr21-1060028019892644","first-page":"54","volume":"61","author":"Esketamine nasal spray (Spravato) for treatment-resistant depression","year":"2019","journal-title":"Med Lett Drugs Ther"},{"key":"bibr22-1060028019892644","unstructured":"US Food and Drug Administration. FDA briefing document. Psychopharmacologic Drugs Advisory Committee (PDAC) and Drug Safety and Risk Management (DSaRM) Advisory Committee Meeting, February 12, 2019. https:\/\/www.fda.gov\/media\/121376\/download. Accessed November 5, 2019."},{"key":"bibr23-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2017.3739"},{"key":"bibr24-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyz039"},{"key":"bibr25-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2019.19020172"},{"key":"bibr26-1060028019892644","unstructured":"Janssen Research & Development LLC. A study to evaluate the efficacy, safety, and tolerability of intranasal esketamine plus an oral antidepressant in elderly participants with treatment-resistant depression (TRANSFORM-3). https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02422186. Accessed November 5, 2019."},{"key":"bibr27-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2019.1189"},{"key":"bibr28-1060028019892644","unstructured":"Janssen Research & Development LLC. A long-term, safety and efficacy study of intranasal esketamine in treatment-resistant depression (SUSTAIN-2). https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02497287. Accessed November 5, 2019."},{"key":"bibr29-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2015.10.018"},{"key":"bibr30-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.17060720"},{"key":"bibr31-1060028019892644","unstructured":"Janssen Research & Development LLC. A study to evaluate the efficacy and safety of intranasal esketamine in addition to comprehensive standard of care for the rapid reduction of the symptoms of major depressive disorder, including suicidal ideation, in adult participants assessed to be at imminent risk for suicide (Aspire I). https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03039192. Accessed November 5, 2019."},{"key":"bibr32-1060028019892644","unstructured":"Janssen Research & Development LLC. A study to evaluate the efficacy and safety of intranasal esketamine in addition to comprehensive standard of care for the rapid reduction of the symptoms of major depressive disorder, including suicidal ideation, in adult participants assessed to be at imminent risk for suicide (Aspire II). https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03097133. Accessed November 5, 2019."},{"key":"bibr33-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1017\/cts.2017.2"},{"key":"bibr34-1060028019892644","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-018-4828-5"},{"key":"bibr35-1060028019892644","unstructured":"Janssen Pharmaceuticals, Inc. SPRAVATO\u2122 REMS (Risk Evaluation and Mitigation Strategy). https:\/\/www.spravatorems.com. Accessed November 5, 2019."},{"key":"bibr36-1060028019892644","unstructured":"Institute for Clinical and Economic Review. Esketamine for the treatment of treatment-resistant depression: effectiveness and value. https:\/\/icer-review.org\/wp-content\/uploads\/2018\/10\/ICER_TRD_Evidence_Report_050919.pdf. Accessed November 5, 2019."},{"key":"bibr37-1060028019892644","unstructured":"Janssen Prescription Assistance. Need help paying for your Spravato\u2122 (esketamine) Nasal Spray CIII medication? http:\/\/www.janssenprescriptionassistance.com\/spravato-cost-assistance. Accessed November 5, 2019."},{"key":"bibr38-1060028019892644","first-page":"29","volume":"12","author":"Lee J","year":"2015","journal-title":"Innov Clin Neurosci"},{"key":"bibr39-1060028019892644","doi-asserted-by":"publisher","DOI":"10.9740\/mhc.2019.01.048"},{"key":"bibr40-1060028019892644","first-page":"554","volume":"31","author":"Galuszko-Wegielnik M","year":"2019","journal-title":"Psychiatr Danub"},{"key":"bibr41-1060028019892644","unstructured":"Celon Pharma SA. Efficacy, safety and pharmacokinetic study of inhaled esketamine in treatment-resistant bipolar depression. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03965871. Accessed November 5, 2019."}],"container-title":["Annals of Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1060028019892644","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1060028019892644","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1060028019892644","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T11:15:19Z","timestamp":1777374919000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1060028019892644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,4]]},"references-count":41,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1177\/1060028019892644"],"URL":"https:\/\/doi.org\/10.1177\/1060028019892644","relation":{},"ISSN":["1060-0280","1542-6270"],"issn-type":[{"value":"1060-0280","type":"print"},{"value":"1542-6270","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,4]]}}}