Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression

Naji C. Salloum, Maurizio Fava, Marlene P. Freeman, Martina Flynn, Bettina Hoeppner, Rebecca S. Hock, 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

4 Citations (Scopus)

Abstract

Objective: To examine the effect of high baseline anxiety on response to ketamine versus midazolam (active placebo) in treatment-resistant depression (TRD). Methods: In a multisite, double-blind, placebo-controlled trial, 99 subjects with TRD were randomized to one of five arms: a single dose of intravenous ketamine 0.1, 0.2, 0.5, 1.0 mg/kg, or midazolam 0.045 mg/kg. The primary outcome measure was change in the six-item Hamilton Rating Scale for Depression (HAMD6). A linear mixed effects model was used to examine the effect of anxious depression baseline status (defined by a Hamilton Depression Rating Scale Anxiety-Somatization score ≥7) on response to ketamine versus midazolam at 1 and 3 days postinfusion. Results: N = 45 subjects had anxious TRD, compared to N = 54 subjects without high anxiety at baseline. No statistically significant interaction effect was found between treatment group assignment (combined ketamine treatment groups versus midazolam) and anxious/nonanxious status on HAMD6 score at either days 1 or 3 postinfusion (Day 1: F(1, 84) = 0.02, P = 0.88; Day 3: F(1, 82) = 0.12, P = 0.73). Conclusion: In contrast with what is observed with traditional antidepressants, response to ketamine may be similar in both anxious and nonanxious TRD subjects. These pilot results suggest the potential utility of ketamine in the treatment of anxious TRD.

Original languageEnglish (US)
JournalDepression and Anxiety
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Treatment-Resistant Depressive Disorder
Ketamine
Midazolam
Anxiety
Depression
Therapeutics
Placebos
Antidepressive Agents
Outcome Assessment (Health Care)

Keywords

  • active placebo
  • anxious depression
  • ketamine
  • major depressive disorder
  • midazolam
  • treatment-resistant depression

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

Cite this

Salloum, N. C., Fava, M., Freeman, M. P., Flynn, M., Hoeppner, B., Hock, R. S., ... Papakostas, G. I. (Accepted/In press). Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression. Depression and Anxiety. https://doi.org/10.1002/da.22875

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

In: Depression and Anxiety, 01.01.2018.

Research output: Contribution to journalArticle

Salloum, NC, Fava, M, Freeman, MP, Flynn, M, Hoeppner, B, Hock, RS, Cusin, C, Iosifescu, DV, Trivedi, MH, Sanacora, G, Mathew, SJ, Debattista, C, Ionescu, DF & Papakostas, GI 2018, 'Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression', Depression and Anxiety. https://doi.org/10.1002/da.22875
Salloum, Naji C. ; Fava, Maurizio ; Freeman, Marlene P. ; Flynn, Martina ; Hoeppner, Bettina ; Hock, Rebecca S. ; Cusin, Cristina ; Iosifescu, Dan V. ; Trivedi, Madhukar H ; Sanacora, Gerard ; Mathew, Sanjay J. ; Debattista, Charles ; Ionescu, Dawn F. ; Papakostas, George I. / Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression. In: Depression and Anxiety. 2018.
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abstract = "Objective: To examine the effect of high baseline anxiety on response to ketamine versus midazolam (active placebo) in treatment-resistant depression (TRD). Methods: In a multisite, double-blind, placebo-controlled trial, 99 subjects with TRD were randomized to one of five arms: a single dose of intravenous ketamine 0.1, 0.2, 0.5, 1.0 mg/kg, or midazolam 0.045 mg/kg. The primary outcome measure was change in the six-item Hamilton Rating Scale for Depression (HAMD6). A linear mixed effects model was used to examine the effect of anxious depression baseline status (defined by a Hamilton Depression Rating Scale Anxiety-Somatization score ≥7) on response to ketamine versus midazolam at 1 and 3 days postinfusion. Results: N = 45 subjects had anxious TRD, compared to N = 54 subjects without high anxiety at baseline. No statistically significant interaction effect was found between treatment group assignment (combined ketamine treatment groups versus midazolam) and anxious/nonanxious status on HAMD6 score at either days 1 or 3 postinfusion (Day 1: F(1, 84) = 0.02, P = 0.88; Day 3: F(1, 82) = 0.12, P = 0.73). Conclusion: In contrast with what is observed with traditional antidepressants, response to ketamine may be similar in both anxious and nonanxious TRD subjects. These pilot results suggest the potential utility of ketamine in the treatment of anxious TRD.",
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AU - Flynn, Martina

AU - Hoeppner, Bettina

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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.

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N2 - Objective: To examine the effect of high baseline anxiety on response to ketamine versus midazolam (active placebo) in treatment-resistant depression (TRD). Methods: In a multisite, double-blind, placebo-controlled trial, 99 subjects with TRD were randomized to one of five arms: a single dose of intravenous ketamine 0.1, 0.2, 0.5, 1.0 mg/kg, or midazolam 0.045 mg/kg. The primary outcome measure was change in the six-item Hamilton Rating Scale for Depression (HAMD6). A linear mixed effects model was used to examine the effect of anxious depression baseline status (defined by a Hamilton Depression Rating Scale Anxiety-Somatization score ≥7) on response to ketamine versus midazolam at 1 and 3 days postinfusion. Results: N = 45 subjects had anxious TRD, compared to N = 54 subjects without high anxiety at baseline. No statistically significant interaction effect was found between treatment group assignment (combined ketamine treatment groups versus midazolam) and anxious/nonanxious status on HAMD6 score at either days 1 or 3 postinfusion (Day 1: F(1, 84) = 0.02, P = 0.88; Day 3: F(1, 82) = 0.12, P = 0.73). Conclusion: In contrast with what is observed with traditional antidepressants, response to ketamine may be similar in both anxious and nonanxious TRD subjects. These pilot results suggest the potential utility of ketamine in the treatment of anxious TRD.

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