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

Y.D. Hu, Y.T. Xiang, J.X. Fang, S. Zu, S. Sha, H. Shi, Gabor Ungvari, C.U. Correll, H.F.K. Chiu, Y. Xue, T.F. Tian, A.S. Wu, X. Ma, G. Wang

    Research output: Contribution to journalArticle

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    Abstract

    © Cambridge University Press 2015.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.
    Original languageEnglish
    Pages (from-to)623-635
    JournalPsychological Medicine
    Volume46
    Issue number3
    DOIs
    Publication statusPublished - 2016

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