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Psychol Med. 2016 Feb;46(3):623-35. doi: 10.1017/S0033291715002159. Epub 2015 Oct 19.

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

Author information

1
China & Beijing Key Laboratory of Mental Disorders,The National Clinical Research Center for Mental Disorders,Beijing Anding Hospital,Capital Medical University,Beijing,China.
2
Unit of Psychiatry,Faculty of Health Sciences,University of Macau,Macao SAR,China.
3
Unit of Psychological Medicine,Beijing Chao-Yang Hospital,Capital Medical University,Beijing,China.
4
The University of Notre Dame Australia/Marian Centre,Perth,Australia.
5
Division of Psychiatry Research,The Zucker Hillside Hospital,North Shore-Long Island Jewish Health System,Glen Oaks,NY,USA.
6
Department of Psychiatry,Chinese University of Hong Kong,Hong Kong SAR,China.

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:

Efficacy; escitalopram; ketamine; major depression; response; tolerability

PMID:
26478208
DOI:
10.1017/S0033291715002159
[Indexed for MEDLINE]

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