Clinical Predictors of Antidepressant Effects of Ketamine and Esketamine in Treatment-Resistant Unipolar and Bipolar Depression: A Systematic Review

Friedrich MJ. Depression is the leading cause of disability around the world. JAMA. 2017;317(15):1517. https://doi.org/10.1001/jama.2017.3826.

Article  PubMed  Google Scholar 

Johnston KM, Powell LC, Anderson IM, Szabo S, Cline S. The burden of treatment-resistant depression: a systematic review of the economic and quality of life literature. J Affect Disord. 2019;242:195–210. https://doi.org/10.1016/j.jad.2018.06.045.

Article  PubMed  Google Scholar 

Cui L, Li S, Wang S, Wu X, Liu Y, Yu W, et al. Major depressive disorder: hypothesis, mechanism, prevention and treatment. Signal Transduct Target Ther. 2024;9(1):30. https://doi.org/10.1038/s41392-024-01738-y.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR* D report. Am J Psychiatry. 2006;163(11):1905–17. https://doi.org/10.1176/ajp.2006.163.11.1905.

Article  PubMed  Google Scholar 

McIntyre RS, Alsuwaidan M, Baune BT, Berk M, Demyttenaere K, Goldberg JF, et al. Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions. World Psychiatry. 2023;22(3):394–412. https://doi.org/10.1002/wps.21120.

Article  PubMed  PubMed Central  Google Scholar 

Li CT, Bai YM, Huang YL, Chen YS, Chen TJ, Cheng JY, et al. Association between antidepressant resistance in unipolar depression and subsequent bipolar disorder: cohort study. Br J Psychiatry. 2012;200(1):45–51. https://doi.org/10.1192/bjp.bp.110.086983.

Article  PubMed  Google Scholar 

Lam RW, Kennedy SH, Adams C, Bahji A, Beaulieu S, Bhat V, et al. Réseau canadien pour les traitements de l’humeur et de l’anxiété (CANMAT) 2023: mise à jour des lignes directrices cliniques pour la prise en charge du trouble dépressif majeur chez les adultes. Can J Psychiatry. 2024;69(9):641–87. https://doi.org/10.1177/07067437241245384.

Article  PubMed  PubMed Central  Google Scholar 

Kendrick T, Pilling S, Mavranezouli I, Megnin-Viggars O, Ruane C, Eadon H, et al. Management of depression in adults: summary of updated NICE guidance. BMJ. 2022;378:o1557. https://doi.org/10.1136/bmj.o1557.

Article  PubMed  Google Scholar 

Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351–4. https://doi.org/10.1016/S0006-3223(99)00230-9.

Article  PubMed  CAS  Google Scholar 

Murrough JW, Perez AM, Pillemer S, Stern J, Parides MK, aan het Rot M, et al. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry. 2013;74(4):250–6. https://doi.org/10.1016/j.biopsych.2012.06.022.

Article  PubMed  CAS  Google Scholar 

Phillips JL, Norris S, Talbot J, Birmingham M, Hatchard T, Ortiz A, et al. Single, repeated, and maintenance ketamine infusions for treatment-resistant depression: a randomized controlled trial. Am J Psychiatry. 2019;176(5):401–9. https://doi.org/10.1176/appi.ajp.2018.18070834.

Article  PubMed  Google Scholar 

Anand A, Mathew SJ, Sanacora G, Murrough JW, Goes FS, Altinay M, et al. Ketamine versus ECT for nonpsychotic treatment-resistant major depression. N Engl J Med. 2023;388(25):2315–25. https://doi.org/10.1056/NEJMoa2302399.

Article  PubMed  CAS  Google Scholar 

Hietamies TM, McInnes LA, Klise AJ, Worley MJ, Qian JJ, Williams LM, et al. The effects of ketamine on symptoms of depression and anxiety in real-world care settings: a retrospective controlled analysis. J Affect Disord. 2023;335:484–92. https://doi.org/10.1016/j.jad.2023.04.141.

Article  PubMed  CAS  Google Scholar 

Rahrig R, Kosikowski K, Whyde H, Devoll K, Honigford A, Davis M, et al. Spravato® FDA-approved as monotherapy for adults with treatment-resistant depression. Pharm Wellness Rev. 2025;16(2):2.

Google Scholar 

Swainson J, McGirr A, Blier P, Brietzke E, Richard-Devantoy S, Ravindran N, et al. The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force recommendations for the use of racemic ketamine in adults with major depressive disorder: recommandations du groupe de travail du réseau canadien pour les traitements de l’humeur et de l’anxiété (canmat) concernant l’utilisation de la kétamine racémique chez les adultes souffrant de trouble dépressif majeur. Can J Psychiatry. 2021;66(2):113–25. https://doi.org/10.1177/104012371202400104.

Article  PubMed  Google Scholar 

Ekstrand J, Takamiya A, Nordenskjold A, Kirov G, Sienaert P, Kellner CH, et al. Ketamine or ECT? What have we learned from the KetECT and ELEKT-D trials? Int J Neuropsychopharmacol. 2024;27(1):pyad065. https://doi.org/10.1093/ijnp/pyad065.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Rhee TG, Shim SR, Forester BP, Nierenberg AA, McIntyre RS, Papakostas GI, et al. Efficacy and safety of ketamine vs electroconvulsive therapy among patients with major depressive episode: a systematic review and meta-analysis. JAMA Psychiat. 2022;79(12):1162–72. https://doi.org/10.1001/jamapsychiatry.2022.3352.

Article  Google Scholar 

Shi ZM, Lan XJ, Chen Q, Chen JJ, Su ZA, Huang XB, et al. Intravenous ketamine versus electroconvulsive therapy for major depressive disorder or bipolar depression: a meta-analysis of randomized controlled trials. J Affect Disord. 2025;371:45–53. https://doi.org/10.1016/j.jad.2024.11.034.

Article  PubMed  CAS  Google Scholar 

Jelovac A, Braithwaite R, McLoughlin DM. Advancing ketamine in the treatment hierarchy for refractory depression: commentary, Jelovac et al. Br J Psychiatry. 2026;228(2):174–5. https://doi.org/10.1192/bjp.2025.10472.

Article  PubMed  Google Scholar 

Elliott SI, Katz BR, Ostroff BR, Ansari M, Holmes SE, Sanacora G. Ketamine versus electroconvulsive therapy for the treatment of depression: a guide for clinicians. Focus. 2025;23(2):195–205. https://doi.org/10.1176/appi.focus.20240040.

Article  PubMed  PubMed Central  Google Scholar 

Simon GE, Perlis RH. Personalized medicine for depression: can we match patients with treatments? Am J Psychiatry. 2010;167(12):1445–55. https://doi.org/10.1176/appi.ajp.2010.09111680.

Article  PubMed  PubMed Central  Google Scholar 

Deif R, Salama M. Depression from a precision mental health perspective: utilizing personalized conceptualizations to guide personalized treatments. Front Psychiatry. 2021;12:650318. https://doi.org/10.3389/fpsyt.2021.650318.

Article  PubMed  PubMed Central  Google Scholar 

Wade BS, Pindale R, Luccarelli J, Li S, Meisner RC, Seiner SJ, et al. Prediction of individual treatment allocation between electroconvulsive therapy or ketamine using the Personalized Advantage Index. NPJ Digit Med. 2025;8(1):127. https://doi.org/10.1038/s41746-025-01523-3.

Article  PubMed  PubMed Central  Google Scholar 

Price RB, Kissel N, Baumeister A, Rohac R, Woody ML, Ballard ED, et al. International pooled patient-level meta-analysis of ketamine infusion for depression: in search of clinical moderators. Mol Psychiatry. 2022;27(12):5096–112. https://doi.org/10.1038/s41380-022-01757-7.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Baminiwatta A, Menon V. Predictors of response to electroconvulsive therapy in major depressive disorder: a review of recent research findings. Curr Behav Neurosci Rep. 2024;11(4):211–22. https://doi.org/10.1007/s40473-024-00286-7.

Article  Google Scholar 

Pinna M, Manchia M, Oppo R, Scano F, Pillai G, Loche AP, et al. Clinical and biological predictors of response to electroconvulsive therapy (ECT): a review. Neurosci Lett. 2018;669:32–42. https://doi.org/10.1016/j.neulet.2016.10.047.

Article  PubMed  CAS  Google Scholar 

Loef D, Hoogendoorn AW, Somers M, Mocking RJ, Scheepens DS, Scheepstra KW, et al. A prediction model for electroconvulsive therapy effectiveness in patients with major depressive disorder from the Dutch ECT Consortium (DEC). Mol Psychiatry. 2025;30(5):1915–24. https://doi.org/10.1038/s41380-024-02803-2.

Article  PubMed  Google Scholar 

Gonterman F. A systematic review assessing patient-related predictors of response to transcranial magnetic stimulation in major depressive disorder. Neuropsychiatr Dis Treat. 2023;19:565–77. https://doi.org/10.2147/NDT.S388164.

Article  PubMed  PubMed Central  Google Scholar 

Rong C, Park C, Rosenblat JD, S

Comments (0)

No login
gif