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Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: results from a randomized, placebo-controlled 4-week study

Published online by Cambridge University Press:  19 October 2015

Y.-D. Hu ,
Y.-T. Xiang ,
J.-X. Fang ,
S. Zu ,
S. Sha ,
H. Shi ,
G. S. Ungvari ,
C. U. Correll ,
H. F. K. Chiu  and
Y. Xue
...Show all authors
Y.-D. Hu
Affiliation:
China & Beijing Key Laboratory of Mental Disorders, The National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China Department of Psychiatry, Capital Medical University, China & Center of Depression, Beijing Institute for Brain Disorders, Beijing, China Unit of Psychological Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
Y.-T. Xiang*
Affiliation:
Unit of Psychiatry, Faculty of Health Sciences, University of Macau, Macao SAR, China
J.-X. Fang
Affiliation:
Unit of Psychological Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
S. Zu
Affiliation:
Unit of Psychological Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
S. Sha
Affiliation:
China & Beijing Key Laboratory of Mental Disorders, The National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
H. Shi
Affiliation:
China & Beijing Key Laboratory of Mental Disorders, The National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China Unit of Psychological Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
G. S. Ungvari
Affiliation:
The University of Notre Dame Australia/Marian Centre, Perth, Australia School of Psychiatry & Clinical Neurosciences, University of Western Australia, Perth, Australia
C. U. Correll
Affiliation:
Division of Psychiatry Research, The Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA
H. F. K. Chiu
Affiliation:
Department of Psychiatry, Chinese University of Hong Kong, Hong Kong SAR, China
Y. Xue
Affiliation:
China & Beijing Key Laboratory of Mental Disorders, The National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
T.-F. Tian
Affiliation:
China & Beijing Key Laboratory of Mental Disorders, The National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
A.-S. Wu
Affiliation:
Unit of Psychological Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
X. Ma
Affiliation:
China & Beijing Key Laboratory of Mental Disorders, The National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China Department of Psychiatry, Capital Medical University, China & Center of Depression, Beijing Institute for Brain Disorders, Beijing, China
G. Wang*
Affiliation:
China & Beijing Key Laboratory of Mental Disorders, The National Clinical Research Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China Department of Psychiatry, Capital Medical University, China & Center of Depression, Beijing Institute for Brain Disorders, Beijing, China
*
*Address for correspondence: Dr G. Wang, Mood Disorders Center, Beijing Anding Hospital, Beijing, China. (Email: [email protected]) [G.W.] (Email: [email protected]) [Y.-T.X.]
*Address for correspondence: Dr G. Wang, Mood Disorders Center, Beijing Anding Hospital, Beijing, China. (Email: [email protected]) [G.W.] (Email: [email protected]) [Y.-T.X.]
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Abstract

Background

While oral antidepressants reach efficacy after weeks, single-dose intravenous (i.v.) ketamine has rapid, yet time-limited antidepressant effects. We aimed to determine the efficacy and safety of single-dose i.v. ketamine augmentation of escitalopram in major depressive disorder (MDD).

Method

Thirty outpatients with severe MDD (17-item Hamilton Rating Scale for Depression total score ⩾24) were randomized to 4 weeks double-blind treatment with escitalopram 10 mg/day+single-dose i.v. ketamine (0.5 mg/kg over 40 min) or escitalopram 10 mg/day + placebo (0.9% i.v. saline). Depressive symptoms were measured using the Montgomery–Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology – Self-Report (QIDS-SR). Suicidal ideation was evaluated with the QIDS-SR item 12. Adverse psychopathological effects were measured with the Brief Psychiatric Rating Scale (BPRS)-positive symptoms, Young Mania Rating Scale (YMRS) and Clinician Administered Dissociative States Scale (CADSS). Patients were assessed at baseline, 1, 2, 4, 24 and 72 h and 7, 14, 21 and 28 days. Time to response (⩾50% MADRS score reduction) was the primary outcome.

Results

By 4 weeks, more escitalopram + ketamine-treated than escitalopram + placebo-treated patients responded (92.3% v. 57.1%, p = 0.04) and remitted (76.9% v. 14.3%, p = 0.001), with significantly shorter time to response [hazard ratio (HR) 0.04, 95% confidence interval (CI) 0.01–0.22, p < 0.001] and remission (HR 0.11, 95% CI 0.02–0.63, p = 0.01). Compared to escitalopram + placebo, escitalopram + ketamine was associated with significantly lower MADRS scores from 2 h to 2 weeks [(peak = 3 days–2 weeks; effect size (ES) = 1.08–1.18)], QIDS-SR scores from 2 h to 2 weeks (maximum ES = 1.27), and QIDS-SR suicidality from 2 to 72 h (maximum ES = 2.24). Only YMRS scores increased significantly with ketamine augmentation (1 and 2 h), without significant BPRS or CADSS elevation.

Conclusions

Single-dose i.v. ketamine augmentation of escitalopram was safe and effective in severe MDD, holding promise for speeding up early oral antidepressant efficacy.

Keywords

Efficacyescitalopramketaminemajor depressionresponsetolerability
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 3 , February 2016 , pp. 623 - 635
Copyright
Copyright © Cambridge University Press 2015 

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