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

Naji C. Salloum, Maurizio Fava, Rebecca S. Hock, Marlene P. Freeman, Martina Flynn, Bettina Hoeppner, Cristina Cusin, Dan V. Iosifescu, Madhukar H Trivedi, Gerard Sanacora, Sanjay J. Mathew, Charles Debattista, Dawn F. Ionescu, George I. Papakostas

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)131-139
Number of pages9
JournalJournal of affective disorders
Volume260
DOIs
StatePublished - Jan 1 2020

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Treatment-Resistant Depressive Disorder
Ketamine
Intravenous Administration
Recurrence
Midazolam
Secondary Prevention
Intravenous Infusions
Sample Size

Keywords

  • Ketamine
  • Major depressive disorder
  • Relapse
  • Remission
  • Treatment-resistant depression

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

Cite this

Time to relapse after a single administration of intravenous ketamine augmentation in unipolar treatment-resistant depression. / Salloum, Naji C.; Fava, Maurizio; Hock, Rebecca S.; Freeman, Marlene P.; Flynn, Martina; Hoeppner, Bettina; Cusin, Cristina; Iosifescu, Dan V.; Trivedi, Madhukar H; Sanacora, Gerard; Mathew, Sanjay J.; Debattista, Charles; Ionescu, Dawn F.; Papakostas, George I.

In: Journal of affective disorders, Vol. 260, 01.01.2020, p. 131-139.

Research output: Contribution to journalArticle

Salloum, NC, Fava, M, Hock, RS, Freeman, MP, Flynn, M, Hoeppner, B, Cusin, C, Iosifescu, DV, Trivedi, MH, Sanacora, G, Mathew, SJ, Debattista, C, Ionescu, DF & Papakostas, GI 2020, 'Time to relapse after a single administration of intravenous ketamine augmentation in unipolar treatment-resistant depression', Journal of affective disorders, vol. 260, pp. 131-139. https://doi.org/10.1016/j.jad.2019.09.017
Salloum, Naji C. ; Fava, Maurizio ; Hock, Rebecca S. ; Freeman, Marlene P. ; Flynn, Martina ; Hoeppner, Bettina ; Cusin, Cristina ; Iosifescu, Dan V. ; Trivedi, Madhukar H ; Sanacora, Gerard ; Mathew, Sanjay J. ; Debattista, Charles ; Ionescu, Dawn F. ; Papakostas, George I. / Time to relapse after a single administration of intravenous ketamine augmentation in unipolar treatment-resistant depression. In: Journal of affective disorders. 2020 ; Vol. 260. pp. 131-139.
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abstract = "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.",
keywords = "Ketamine, Major depressive disorder, Relapse, Remission, Treatment-resistant depression",
author = "Salloum, {Naji C.} and Maurizio Fava and Hock, {Rebecca S.} and Freeman, {Marlene P.} and Martina Flynn and Bettina Hoeppner and Cristina Cusin and Iosifescu, {Dan V.} and Trivedi, {Madhukar H} and Gerard Sanacora and Mathew, {Sanjay J.} and Charles Debattista and Ionescu, {Dawn F.} and Papakostas, {George I.}",
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T1 - Time to relapse after a single administration of intravenous ketamine augmentation in unipolar treatment-resistant depression

AU - Salloum, Naji C.

AU - Fava, Maurizio

AU - Hock, Rebecca S.

AU - Freeman, Marlene P.

AU - Flynn, Martina

AU - Hoeppner, Bettina

AU - Cusin, Cristina

AU - Iosifescu, Dan V.

AU - Trivedi, Madhukar H

AU - Sanacora, Gerard

AU - Mathew, Sanjay J.

AU - Debattista, Charles

AU - Ionescu, Dawn F.

AU - Papakostas, George I.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - 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.

AB - 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.

KW - Ketamine

KW - Major depressive disorder

KW - Relapse

KW - Remission

KW - Treatment-resistant depression

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