Time to relapse after a single administration of intravenous ketamine augmentation in unipolar treatment-resistant depression

JOURNAL OF AFFECTIVE DISORDERS

卷:260

Article

Salloum, Naji C.^1,2  Fava, Maurizio^1,2  Hock, Rebecca S.¹  Freeman, Marlene P.^1,2  Flynn, Martina^1,2  Hoeppner, Bettina¹  Cusin, Cristina¹  Iosifescu, Dan V.³  Trivedi, Madhukar H.⁴  Sanacora, Gerard⁵  Mathew, Sanjay J.^6,7  Debattista, Charles⁸  Ionescu, Dawn F.^1,9  Papakostas, George I.^1,2 

[1] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA

[2] Massachusetts Gen Hosp, Clin Trials Network & Inst, Boston, MA 02114 USA

[3] NYU, Sch Med, Nathan Kline Inst, New York, NY 10003 USA

[4] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA

[5] Yale Sch Med, New Haven, CT USA

[6] Baylor Coll Med, Houston, TX 77030 USA

[7] Michael E Debakey VA Med Ctr, Houston, TX USA

[8] Stanford Univ, Sch Med, Stanford, CA 94305 USA

[9] Janssen Pharmaceut Res & Dev, La Jolla, CA USA

关键词: Major depressive disorder;    Treatment-resistant depression;    Ketamine;    Remission;    Relapse;   

DOI  :  10.1016/j.jad.2019.09.017

来源: Elsevier

【 摘 要 】

Objective: To examine the rate and time to relapse for remitters and responders to ketamine in treatment-resistant depression (TRD). Methods: Subjects with TRD were randomized to a single infusion of one of several doses of intravenous ketamine, or midazolam. Using Kaplan-Meier survival function, the current report examines the rate and time to relapse, defined as MADRS >= 22, over a period of 30 days, in subjects who achieved remission (MADRS <= 10) or response ( 50% >= reduction in MADRS) on day three post-infusion of intravenous ketamine 0.1, 0.5, or 1.0 mg/kg. Results: Of the 60 randomized participants who received a single ketamine (0.1, 0.5, or 1.0 mg/kg) infusion, 19 (34%) met criteria for remission and 27 (48%) for response, on day 3 post-infusion. A numerical dose-response relationship was observed, with remitters/responders on ketamine 1.0 mg/kg having the lowest relapse rate, followed by ketamine 0.5 mg/kg and 0.1 mg/kg, respectively (% of remitters who relapsed by day 14: 38% with 1.0 mg/kg, 50% with 0.5 mg/kg, 100% with 0.1 mg/kg;% of responders who relapsed by day 14: 30% with 1.0 mg/kg, 50% with 0.5 mg/kg, 80% with 0.1 mg/kg). Limitations: The sample size was small. No MADRS measurements at day one post-infusion. The study was not powered to assess differences in relapse prevention between different doses of ketamine. Conclusion: Time to relapse after successful treatment with a single infusion of ketamine appears to follow a dose-response relationship, where higher dosage leads to increased time to relapse.

【 授权许可】

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