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

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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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    Citalopram
    Ketamine
    Placebos
    Depression
    Self Report
    Major Depressive Disorder
    Antidepressive Agents
    Brief Psychiatric Rating Scale
    Equipment and Supplies
    Bipolar Disorder
    Confidence Intervals
    Suicidal Ideation
    Outpatients
    Safety

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    Hu, Y.D. ; Xiang, Y.T. ; Fang, J.X. ; Zu, S. ; Sha, S. ; Shi, H. ; Ungvari, Gabor ; Correll, C.U. ; Chiu, H.F.K. ; Xue, Y. ; Tian, T.F. ; Wu, A.S. ; Ma, X. ; Wang, G. / Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: Results from a randomized, placebo-controlled 4-week study. In: Psychological Medicine. 2016 ; Vol. 46, No. 3. pp. 623-635.
    @article{2ef998e431124e5caa337ee3cbbd5986,
    title = "Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: Results from a randomized, placebo-controlled 4-week study",
    abstract = "{\circledC} 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.",
    author = "Y.D. Hu and Y.T. Xiang and J.X. Fang and S. Zu and S. Sha and H. Shi and Gabor Ungvari and C.U. Correll and H.F.K. Chiu and Y. Xue and T.F. Tian and A.S. Wu and X. Ma and G. Wang",
    year = "2016",
    doi = "10.1017/S0033291715002159",
    language = "English",
    volume = "46",
    pages = "623--635",
    journal = "Psychological Medicine.",
    issn = "0033-2917",
    publisher = "Cambridge University Press",
    number = "3",

    }

    Hu, YD, Xiang, YT, Fang, JX, Zu, S, Sha, S, Shi, H, Ungvari, G, Correll, CU, Chiu, HFK, Xue, Y, Tian, TF, Wu, AS, Ma, X & Wang, G 2016, 'Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: Results from a randomized, placebo-controlled 4-week study' Psychological Medicine, vol. 46, no. 3, pp. 623-635. https://doi.org/10.1017/S0033291715002159

    Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: Results from a randomized, placebo-controlled 4-week study. / Hu, Y.D.; Xiang, Y.T.; Fang, J.X.; Zu, S.; Sha, S.; Shi, H.; Ungvari, Gabor; Correll, C.U.; Chiu, H.F.K.; Xue, Y.; Tian, T.F.; Wu, A.S.; Ma, X.; Wang, G.

    In: Psychological Medicine, Vol. 46, No. 3, 2016, p. 623-635.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: Results from a randomized, placebo-controlled 4-week study

    AU - Hu, Y.D.

    AU - Xiang, Y.T.

    AU - Fang, J.X.

    AU - Zu, S.

    AU - Sha, S.

    AU - Shi, H.

    AU - Ungvari, Gabor

    AU - Correll, C.U.

    AU - Chiu, H.F.K.

    AU - Xue, Y.

    AU - Tian, T.F.

    AU - Wu, A.S.

    AU - Ma, X.

    AU - Wang, G.

    PY - 2016

    Y1 - 2016

    N2 - © 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.

    AB - © 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.

    U2 - 10.1017/S0033291715002159

    DO - 10.1017/S0033291715002159

    M3 - Article

    VL - 46

    SP - 623

    EP - 635

    JO - Psychological Medicine.

    JF - Psychological Medicine.

    SN - 0033-2917

    IS - 3

    ER -