Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation: A randomized, double blind, placebo controlled trial

Dawn F. Ionescu, Kate H. Bentley, Matthias Eikermann, Norman Taylor, Oluwaseun Johnson-Akeju, Michaela B. Swee, Kara J. Pavone, Samuel R. Petrie, Christina Dording, David Mischoulon, Jonathan E. Alpert, Emery N. Brown, Lee Baer, Matthew K. Nock, Maurizio Fava, Cristina Cusin

Research output: Contribution to journalArticle

Abstract

Background: Several studies indicate that ketamine has rapid antidepressant effects in patients with treatment-resistant depression (TRD). The extent to which repeated doses of ketamine (versus placebo) reduce depression in the short and long term among outpatients with TRD and chronic, current suicidal ideation remains unknown. Methods: Twenty-six medicated outpatients with severe major depressive disorder with current, chronic suicidal ideation were randomized in a double-blind fashion to six ketamine infusions (0.5 mg/kg over 45 minutes) or saline placebo over three weeks. Depression and suicidal ideation were assessed at baseline, 240 min post-infusion, and during a three-month follow-up phase. Results: During the infusion phase, there was no differences in depression severity or suicidal ideation between placebo and ketamine (p = 0.47 and p = 0.32, respectively). At the end of the infusion phase, two patients in the ketamine group and one in the placebo group met criteria for remission of depression. At three-month follow-up, two patients in each group met criteria for remission from depression. Limitations: Limitations include the small sample size, uncontrolled outpatient medication regimens, and restriction to outpatients, which may have resulted in lower levels of suicidal ideation than would be seen in emergency or inpatient settings. Conclusions: Repeated, non-escalating doses of ketamine did not outperform placebo in this double-blind, placebo controlled study of patients with severe TRD and current, chronic suicidal ideation. This result may support our previously published open-label data that, in this severely and chronically ill outpatient population, the commonly used dose of 0.5 mg/kg is not sufficient.

LanguageEnglish (US)
Pages516-524
Number of pages9
JournalJournal of Affective Disorders
Volume243
DOIs
StatePublished - Jan 15 2019

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Treatment-Resistant Depressive Disorder
Suicidal Ideation
Ketamine
Placebos
Outpatients
Depression
Major Depressive Disorder
Sample Size
Antidepressive Agents
Inpatients
Emergencies
Chronic Disease
Population

Keywords

  • Ketamine
  • Repeat-doses
  • Suicidal ideation
  • Treatment-resistant depression

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

Cite this

Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation : A randomized, double blind, placebo controlled trial. / Ionescu, Dawn F.; Bentley, Kate H.; Eikermann, Matthias; Taylor, Norman; Johnson-Akeju, Oluwaseun; Swee, Michaela B.; Pavone, Kara J.; Petrie, Samuel R.; Dording, Christina; Mischoulon, David; Alpert, Jonathan E.; Brown, Emery N.; Baer, Lee; Nock, Matthew K.; Fava, Maurizio; Cusin, Cristina.

In: Journal of Affective Disorders, Vol. 243, 15.01.2019, p. 516-524.

Research output: Contribution to journalArticle

Ionescu, DF, Bentley, KH, Eikermann, M, Taylor, N, Johnson-Akeju, O, Swee, MB, Pavone, KJ, Petrie, SR, Dording, C, Mischoulon, D, Alpert, JE, Brown, EN, Baer, L, Nock, MK, Fava, M & Cusin, C 2019, 'Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation: A randomized, double blind, placebo controlled trial' Journal of Affective Disorders, vol. 243, pp. 516-524. https://doi.org/10.1016/j.jad.2018.09.037
Ionescu, Dawn F. ; Bentley, Kate H. ; Eikermann, Matthias ; Taylor, Norman ; Johnson-Akeju, Oluwaseun ; Swee, Michaela B. ; Pavone, Kara J. ; Petrie, Samuel R. ; Dording, Christina ; Mischoulon, David ; Alpert, Jonathan E. ; Brown, Emery N. ; Baer, Lee ; Nock, Matthew K. ; Fava, Maurizio ; Cusin, Cristina. / Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation : A randomized, double blind, placebo controlled trial. In: Journal of Affective Disorders. 2019 ; Vol. 243. pp. 516-524.
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AU - Taylor, Norman

AU - Johnson-Akeju, Oluwaseun

AU - Swee, Michaela B.

AU - Pavone, Kara J.

AU - Petrie, Samuel R.

AU - Dording, Christina

AU - Mischoulon, David

AU - Alpert, Jonathan E.

AU - Brown, Emery N.

AU - Baer, Lee

AU - Nock, Matthew K.

AU - Fava, Maurizio

AU - Cusin, Cristina

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N2 - Background: Several studies indicate that ketamine has rapid antidepressant effects in patients with treatment-resistant depression (TRD). The extent to which repeated doses of ketamine (versus placebo) reduce depression in the short and long term among outpatients with TRD and chronic, current suicidal ideation remains unknown. Methods: Twenty-six medicated outpatients with severe major depressive disorder with current, chronic suicidal ideation were randomized in a double-blind fashion to six ketamine infusions (0.5 mg/kg over 45 minutes) or saline placebo over three weeks. Depression and suicidal ideation were assessed at baseline, 240 min post-infusion, and during a three-month follow-up phase. Results: During the infusion phase, there was no differences in depression severity or suicidal ideation between placebo and ketamine (p = 0.47 and p = 0.32, respectively). At the end of the infusion phase, two patients in the ketamine group and one in the placebo group met criteria for remission of depression. At three-month follow-up, two patients in each group met criteria for remission from depression. Limitations: Limitations include the small sample size, uncontrolled outpatient medication regimens, and restriction to outpatients, which may have resulted in lower levels of suicidal ideation than would be seen in emergency or inpatient settings. Conclusions: Repeated, non-escalating doses of ketamine did not outperform placebo in this double-blind, placebo controlled study of patients with severe TRD and current, chronic suicidal ideation. This result may support our previously published open-label data that, in this severely and chronically ill outpatient population, the commonly used dose of 0.5 mg/kg is not sufficient.

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