Efficacy of repeated intravenous esketamine in adolescents with anxious versus non-anxious depression

Background Patients with anxious major depressive disorder(MDD)are more likely to have poorer outcomes than those with non-anxious MDD.However,the effect of esketamine on adolescents with anxious versus non-anxious MDD has remained unknown.Aims We compared the efficacy of esketamine in adolescents with MDD and suicidal ideation,both anxious and non-anxious.Methods Fifty-four adolescents with anxious(n=33)and non-anxious(n=21)MDD received three infusions of esketamine 0.25mg/kg or active-placebo(midazolam 0.045 mg/kg)over 5 days,with routine inpatient care and treatment.Suicidal ideation and depressive symptoms were assessed using the Columbia Suicide Severity Rating Scale and the Montgomery-Asberg Depression Rating Scale.Multiple-sample proportional tests were used to compare the differences between groups on treatment outcomes 24 hours after the final infusion(day 6,primacy efficacy endpoint)and throughout the 4-week post-treatment(days 12,19 and 33).Results In subjects who received esketamine,a greater number of patients in the non-anxious group than the anxious group achieved antisuicidal remission on day 6(72.7%vs 18.8%,p=0.015)and day 12(90.9%vs 43.8%,p=0.013),and the non-anxious group had a higher antidepressant remission rate compared with the anxious group on day 33(72.7%vs 26.7%,p=0.045).No significant differences in treatment outcomes were observed between the anxious and non-anxious groups at other time points.Conclusions Three infusions of esketamine as an adjunct to routine inpatient care and treatment had a greater immediate post-treatment antisuicidal effect in adolescents with non-anxious MDD than in those with anxious MDD;however,this benefit was temporary and was not maintained over time.

Adjunctive Peony-Glycyrrhiza decoction for antipsychotic-induced hyperprolactinaemia:a meta-analysis of randomised controlled trials

Background Hyperprolactinaemia is a common adverse effect of antipsychotics(APs). The results of PeonyGlycyrrhiza decoction(PGD) as a potentially useful adjunctive treatment for hyperprolactinaemia are inconsistent.Aim This meta-analysis of randomised controlled trials(RCTs) examined the efficacy and safety of adjunctive PGD therapy for AP-induced hyperprolactinaemia.Methods English(PubMed, Embase, Cochrane Library,PsycINFO) and Chinese(Chinese National Knowledge Infrastructure, Wanfang Data) databases were systematically searched up to 10 June 2018. The inclusion criteria were based on PIC0 S一/^rticipants: adult patients with schizophrenia; Aitervention: PGD plus APs; Cbmparison: APs plus placebo or AP monotherapy;(Xjtcomes: efficacy and safety; Study design: RCTs. The weighted mean difference(WMD) and risk ratio(RR) along with their 95% CIs were calculated using Review Manager(RevMan) V.5.3 software.Results Five RCTs(n=450) were included and analysed.Two RCTs(n=140) were double-blind and four RCTs(n=409) reported ‘random' assignment with specific description. The PGD group showed a significantly lower serum prolactin level at endpoint than the control group(n=380, WMD:-32.69 ng/mL(95% Cl-41.66 to 23.72),/X0.00001, ^=97%). Similarly, the superiority of PGD over the control groups was also found in the improvement of hyperprolactinaemia-related symptoms. No difference was found in the improvement of psychiatric symptoms assessed by the Positive and Negative Syndrome Scale(n=403,WMD:-0.62(95% Cl-2.38 to 1.15), p=0.49, ^=0%). There were similar rates of all-cause discontinuation(n=330, RR0.93(95% Ci 0.63 to 1.37),/t=0.71, ^=0%) and adverse drug reactions between the two groups. According to the Grading of Recommendations Assessment, Development and Evaluation approach, the level of evidence of primary and secondary outcomes ranged from ‘very low'(14.3%),‘low'(42.8%),‘moderate'(14.3%),to ‘high,(28.6%>.Conclusions Current evidence supports the adjunctive use of PGD to suppress elevated prolactin and improve prolactininduced symptoms without significant adverse events in adult patients with AP-induced hyperprolactinaemia. Highquality RCTs with longer duration are needed to confirm these findings.Trial registration number 42016037017.