Rapid and sustained reductions in current suicidal ideation following repeated doses of intravenous ketamine

Secondary analysis of an open-label study

Dawn F. Ionescu, Michaela B. Swee, Kara J. Pavone, Norman Taylor, Oluwaseun Akeju, Lee Baer, Maren Nyer, Paolo Cassano, David Mischoulon, Jonathan E. Alpert, Emery N. Brown, Matthew K. Nock, Maurizio Fava, Cristina Cusin

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Background: Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depressed patients with current suicidal ideation remains unknown. Methods: Between April 2012 and October 2013, 14 outpatients with DSM-IV-diagnosed major depressive disorder were recruited for the presence of current, stable (≥3 months) suicidal thoughts. They received open-label ketamine infusions over 3 weeks (0.5 mg/kg over 45 minutes for the first 3 infusions; 0.75 mg/kg over 45 minutes for the last 3). In this secondary analysis, the primary outcome measures of suicidal ideation (Columbia-Suicide Severity Rating Scale [C-SSRS] and the Suicide Item of the 28-item Hamilton Depression Rating Scale [HDRS28-SI]) were assessed at 240 minutes postinfusion and for 3 months thereafter in a naturalistic follow-up. Results: Over the course of the infusions (acute treatment phase), 7 of 14 patients (50%) showed remission of suicidal ideation on the C-SSRS Ideation scale (even among patients whose depression did not remit). There was a significant linear decrease in this score over time (P 〈 .001), which approached significance even after controlling for severity of 6-item Hamilton Depression Rating Scale (HDRS6) core depression items (P = .05). Similarly, there were significant decreases in the C-SSRS Intensity (P 〈 .01) and HDRS28-SI (P 〈 .001) scores during the acute treatment phase. Two of the 7 patients who achieved remission during the acute treatment phase (29%) maintained their remission throughout a 3-month naturalistic follow-up. Conclusions: In this preliminary study, repeated doses of openlabel ketamine rapidly and robustly decreased suicidal ideation in pharmacologically treated outpatients with treatment-resistant depression with stable suicidal thoughts; this decrease was maintained for at least 3 months following the final ketamine infusion in 2 patients.

Original languageEnglish (US)
Pages (from-to)e719-e725
JournalJournal of Clinical Psychiatry
Volume77
Issue number6
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

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Suicidal Ideation
Ketamine
Suicide
Depression
Treatment-Resistant Depressive Disorder
Outpatients
Major Depressive Disorder
Diagnostic and Statistical Manual of Mental Disorders
Therapeutics
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Rapid and sustained reductions in current suicidal ideation following repeated doses of intravenous ketamine : Secondary analysis of an open-label study. / Ionescu, Dawn F.; Swee, Michaela B.; Pavone, Kara J.; Taylor, Norman; Akeju, Oluwaseun; Baer, Lee; Nyer, Maren; Cassano, Paolo; Mischoulon, David; Alpert, Jonathan E.; Brown, Emery N.; Nock, Matthew K.; Fava, Maurizio; Cusin, Cristina.

In: Journal of Clinical Psychiatry, Vol. 77, No. 6, 01.06.2016, p. e719-e725.

Research output: Contribution to journalArticle

Ionescu, DF, Swee, MB, Pavone, KJ, Taylor, N, Akeju, O, Baer, L, Nyer, M, Cassano, P, Mischoulon, D, Alpert, JE, Brown, EN, Nock, MK, Fava, M & Cusin, C 2016, 'Rapid and sustained reductions in current suicidal ideation following repeated doses of intravenous ketamine: Secondary analysis of an open-label study', Journal of Clinical Psychiatry, vol. 77, no. 6, pp. e719-e725. https://doi.org/10.4088/JCP.15m10056
Ionescu, Dawn F. ; Swee, Michaela B. ; Pavone, Kara J. ; Taylor, Norman ; Akeju, Oluwaseun ; Baer, Lee ; Nyer, Maren ; Cassano, Paolo ; Mischoulon, David ; Alpert, Jonathan E. ; Brown, Emery N. ; Nock, Matthew K. ; Fava, Maurizio ; Cusin, Cristina. / Rapid and sustained reductions in current suicidal ideation following repeated doses of intravenous ketamine : Secondary analysis of an open-label study. In: Journal of Clinical Psychiatry. 2016 ; Vol. 77, No. 6. pp. e719-e725.
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abstract = "Background: Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depressed patients with current suicidal ideation remains unknown. Methods: Between April 2012 and October 2013, 14 outpatients with DSM-IV-diagnosed major depressive disorder were recruited for the presence of current, stable (≥3 months) suicidal thoughts. They received open-label ketamine infusions over 3 weeks (0.5 mg/kg over 45 minutes for the first 3 infusions; 0.75 mg/kg over 45 minutes for the last 3). In this secondary analysis, the primary outcome measures of suicidal ideation (Columbia-Suicide Severity Rating Scale [C-SSRS] and the Suicide Item of the 28-item Hamilton Depression Rating Scale [HDRS28-SI]) were assessed at 240 minutes postinfusion and for 3 months thereafter in a naturalistic follow-up. Results: Over the course of the infusions (acute treatment phase), 7 of 14 patients (50{\%}) showed remission of suicidal ideation on the C-SSRS Ideation scale (even among patients whose depression did not remit). There was a significant linear decrease in this score over time (P 〈 .001), which approached significance even after controlling for severity of 6-item Hamilton Depression Rating Scale (HDRS6) core depression items (P = .05). Similarly, there were significant decreases in the C-SSRS Intensity (P 〈 .01) and HDRS28-SI (P 〈 .001) scores during the acute treatment phase. Two of the 7 patients who achieved remission during the acute treatment phase (29{\%}) maintained their remission throughout a 3-month naturalistic follow-up. Conclusions: In this preliminary study, repeated doses of openlabel ketamine rapidly and robustly decreased suicidal ideation in pharmacologically treated outpatients with treatment-resistant depression with stable suicidal thoughts; this decrease was maintained for at least 3 months following the final ketamine infusion in 2 patients.",
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T1 - Rapid and sustained reductions in current suicidal ideation following repeated doses of intravenous ketamine

T2 - Secondary analysis of an open-label study

AU - Ionescu, Dawn F.

AU - Swee, Michaela B.

AU - Pavone, Kara J.

AU - Taylor, Norman

AU - Akeju, Oluwaseun

AU - Baer, Lee

AU - Nyer, Maren

AU - Cassano, Paolo

AU - Mischoulon, David

AU - Alpert, Jonathan E.

AU - Brown, Emery N.

AU - Nock, Matthew K.

AU - Fava, Maurizio

AU - Cusin, Cristina

PY - 2016/6/1

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N2 - Background: Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depressed patients with current suicidal ideation remains unknown. Methods: Between April 2012 and October 2013, 14 outpatients with DSM-IV-diagnosed major depressive disorder were recruited for the presence of current, stable (≥3 months) suicidal thoughts. They received open-label ketamine infusions over 3 weeks (0.5 mg/kg over 45 minutes for the first 3 infusions; 0.75 mg/kg over 45 minutes for the last 3). In this secondary analysis, the primary outcome measures of suicidal ideation (Columbia-Suicide Severity Rating Scale [C-SSRS] and the Suicide Item of the 28-item Hamilton Depression Rating Scale [HDRS28-SI]) were assessed at 240 minutes postinfusion and for 3 months thereafter in a naturalistic follow-up. Results: Over the course of the infusions (acute treatment phase), 7 of 14 patients (50%) showed remission of suicidal ideation on the C-SSRS Ideation scale (even among patients whose depression did not remit). There was a significant linear decrease in this score over time (P 〈 .001), which approached significance even after controlling for severity of 6-item Hamilton Depression Rating Scale (HDRS6) core depression items (P = .05). Similarly, there were significant decreases in the C-SSRS Intensity (P 〈 .01) and HDRS28-SI (P 〈 .001) scores during the acute treatment phase. Two of the 7 patients who achieved remission during the acute treatment phase (29%) maintained their remission throughout a 3-month naturalistic follow-up. Conclusions: In this preliminary study, repeated doses of openlabel ketamine rapidly and robustly decreased suicidal ideation in pharmacologically treated outpatients with treatment-resistant depression with stable suicidal thoughts; this decrease was maintained for at least 3 months following the final ketamine infusion in 2 patients.

AB - Background: Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depressed patients with current suicidal ideation remains unknown. Methods: Between April 2012 and October 2013, 14 outpatients with DSM-IV-diagnosed major depressive disorder were recruited for the presence of current, stable (≥3 months) suicidal thoughts. They received open-label ketamine infusions over 3 weeks (0.5 mg/kg over 45 minutes for the first 3 infusions; 0.75 mg/kg over 45 minutes for the last 3). In this secondary analysis, the primary outcome measures of suicidal ideation (Columbia-Suicide Severity Rating Scale [C-SSRS] and the Suicide Item of the 28-item Hamilton Depression Rating Scale [HDRS28-SI]) were assessed at 240 minutes postinfusion and for 3 months thereafter in a naturalistic follow-up. Results: Over the course of the infusions (acute treatment phase), 7 of 14 patients (50%) showed remission of suicidal ideation on the C-SSRS Ideation scale (even among patients whose depression did not remit). There was a significant linear decrease in this score over time (P 〈 .001), which approached significance even after controlling for severity of 6-item Hamilton Depression Rating Scale (HDRS6) core depression items (P = .05). Similarly, there were significant decreases in the C-SSRS Intensity (P 〈 .01) and HDRS28-SI (P 〈 .001) scores during the acute treatment phase. Two of the 7 patients who achieved remission during the acute treatment phase (29%) maintained their remission throughout a 3-month naturalistic follow-up. Conclusions: In this preliminary study, repeated doses of openlabel ketamine rapidly and robustly decreased suicidal ideation in pharmacologically treated outpatients with treatment-resistant depression with stable suicidal thoughts; this decrease was maintained for at least 3 months following the final ketamine infusion in 2 patients.

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