Journal Article

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

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

2016

Overview

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

• Publisher: Cambridge University Press
• Subject: Administration, Intravenous / Adolescent / Adult / Affective disorders / Antidepressants / Antidepressive Agents - administration & dosage / Antidepressive Agents - adverse effects / Augmentation / China / Citalopram / Citalopram - administration & dosage / Citalopram - adverse effects / Depression / Depressive Disorder, Major - drug therapy / Depressive personality disorders / Dosage / Double-Blind Method / Drug Administration Schedule / Efficacy / Elevation / Female / Holding / Humans / Ideation / Intravenous administration / Kaplan-Meier Estimate / Ketamine / Ketamine - administration & dosage / Ketamine - adverse effects / Male / Mania / Measures / Mental depression / Middle Aged / Original Articles / Outpatients / Patients / Personality Inventory / Proportional Hazards Models / Psychiatric Status Rating Scales / Psychiatry / Psychopathology / Ratings & rankings / Remission / Remission (Medicine) / Safety / Self destructive behavior / Self evaluation / Self Report / Severity of Illness Index / Speeding / Studies / Suicidal ideation / Suicide / Symptoms / Treatment Outcome / Young Adult