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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.
Psychol Med 2016; 46(3):623-35PM

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26478208

Citation

Hu, Y-D, et al. "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, 2016, pp. 623-35.
Hu YD, Xiang YT, Fang JX, et al. Single i.v. ketamine augmentation of newly initiated escitalopram for major depression: results from a randomized, placebo-controlled 4-week study. Psychol Med. 2016;46(3):623-35.
Hu, Y. D., Xiang, Y. T., Fang, J. X., Zu, S., Sha, S., Shi, H., ... 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, 46(3), pp. 623-35. doi:10.1017/S0033291715002159.
Hu YD, et al. Single I.v. Ketamine Augmentation of Newly Initiated Escitalopram for Major Depression: Results From a Randomized, Placebo-controlled 4-week Study. Psychol Med. 2016;46(3):623-35. PubMed PMID: 26478208.
* Article titles in AMA citation format should be in sentence-case
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,G S, 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, Y1 - 2015/10/19/ PY - 2015/10/20/entrez PY - 2015/10/20/pubmed PY - 2016/9/28/medline KW - Efficacy KW - escitalopram KW - ketamine KW - major depression KW - response KW - tolerability SP - 623 EP - 35 JF - Psychological medicine JO - Psychol Med VL - 46 IS - 3 N2 - 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. SN - 1469-8978 UR - https://www.unboundmedicine.com/medline/citation/26478208/Single_i_v__ketamine_augmentation_of_newly_initiated_escitalopram_for_major_depression:_results_from_a_randomized_placebo_controlled_4_week_study_ L2 - https://www.cambridge.org/core/product/identifier/S0033291715002159/type/journal_article DB - PRIME DP - Unbound Medicine ER -