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

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.

[Relationship and significance among IL-6,PI3K/Akt and GSK 3ß in chronic rhinosinusitis].

Objective:To explore the relationship and significance among the expressions of cytokines IL-6，PI3K/Akt signaling transduction pathway, and GSK3ß in chronic rhinosinusitis.Method:The proteins for IL-6,PI3K,Akt,GSK3ß were assayed by Western blot, and mRNAs of cytokines IL-6,IL-6 receptor were measured by real-time quantitative polymerase chain reaction(qPCR) in nasal tissue from the patients with chronic rhinosinusitis with nasal polyps(CRSwNP),chronic rhinosinusitis without nasal polyps(CRSsNP) and control subjects. Result:IL-6,PI3K,Akt,GSK3ß proteins in CRS were higher than those in the control subjects, the differences were statistically significant(P<0.05). There was no significant difference between the groups of CRSsNP and CRSwNP. There were significant differences of cytokines IL-6 mRNA expression between CRSsNP, CRSwNP and control group(P<0.05).IL-6 exists in two forms glycosylated(55 kd) and non-glycosylated(25 kd) in CRS. CRSsNP group mainly glycosylated (glycosylated and non-glycosylated protein expression ratio is about 2.4：1)，CRSwNP group mainly non-glycosylated(glycosylated and non-glycosylated protein expression ratio values about 0.4：1).There was a positive correlation trend among the expressions of IL-6,PI3K,Akt and GSK3ß in CRS. Conclusion:The abnormal expressions of IL-6,PI3K,Akt and GSK3ß in the nasal mucosa of CRS may play a pro-inflammatory role in the occurrence and development of CRS. The glycosylated IL-6 and the non-glycosylated IL-6 may be both involved in the inflammation of CRS.