Effects of ketamine in electroconvulsive therapy for major depressive disorder:meta-analysis of randomised controlled trials

Background The use of ketamine in electroconvulsive therapy(ECT)has been examined in the treatment of major depressive disorder(MDD);however,there has been no systematic review and meta-analysis of related randomised controlled trials(RCTs).Aim To examine the efficacy and safety of ketamine augmentation of ECT in MDD treatment.Methods Two reviewers searched Chinese(China National Knowledge Infrastructure and Wanfang)and English(PubMed,PsycINFO,Embase and Cochrane Library)databases from their inception to 23 July 2019.The included studies'bias risk was evaluated using the Cochrane risk of bias assessment tool.The primary outcome of this metaanalysis was improved d印ressive symptoms at day 1 after a single ECT treatment session.Data were pooled to calculate the standardised mean difference and risk ratio with their 95%CIs using RevMan V.5.3.We used the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)approach to assess the whole quality of evidence.Results Four RCTs(n=239)compared ketamine alone or ketamine plus propofol(n=149)versus propofol alone(n=90)in patients with MDD who underwent a single ECT session.Three RCTs were considered as unclear risk with respect to random sequence generation using the Cochrane risk of bias.Compared with propofol alone,ketamine alone and the combination of ketamine and propofol had greater efficacy in the treatment of depressive symptoms at days 1,3 and 7 after a single ECT session.Moreover,compared with propofol alone,ketamine alone and the combination of ketamine and propofol were significantly associated with increased seizure duration and seizure energy index.Compared with propofol,ketamine alone was significantly associated with increased opening-eye time.Based on the GRADE approach,the evidence level of primary and secondary outcomes ranged from very low(26.7%,4/15)to‘low'(73.3%,11/15).Conclusion Compared with propofol,there were very low or low evidence levels showing that ketamine alone and the combination of ketamine and propofol appeared to rapidly improve depressive symptoms of patients with MDD undergoing a single ECT session.There is a need for highquality RCTs.

Antidepressants combined with psychodrama improve the coping style and cognitive control network in patients with childhood trauma-associated major depressive disorder

BACKGROUND The use of antidepressant therapy alone has a limited efficacy in patients with childhood trauma-associated major depressive disorder(MDD).However,the effectiveness of antidepressant treatment combined with psychodrama in these patients is unclear.AIM To evaluate the effectiveness of antidepressant treatment combined with psychodrama.METHODS Patients with childhood trauma-associated MDD treated with antidepressants were randomly assigned to either the psychodrama intervention(observation group)or the general health education intervention(control group)and received combination treatment for 6 mo.The observation group received general health education given by the investigator together with the“semi-structured group intervention model”of Yi Shu psychodrama.A total of 46 patients were recruited,including 29 cases in the observation group and 17 cases in the control group.Symptoms of depression and anxiety as well as coping style and resting-state functional magnetic resonance imaging were assessed before and after the intervention.RESULTS Symptoms of depression and anxiety,measured by the Hamilton Depression Scale,Beck Depression Inventory,and Beck Anxiety Inventory,were reduced after the intervention in both groups of patients.The coping style of the observation group improved significantly in contrast to the control group,which did not.In addition,an interaction between treatment and time in the right superior parietal gyrus node was found.Furthermore,functional connectivity between the right superior parietal gyrus and left inferior frontal gyrus in the observation group increased after the intervention,while in the control group the connectivity decreased.CONCLUSION This study supports the use of combined treatment with antidepressants and psychodrama to improve the coping style of patients with childhood trauma-associated MDD.Functional connectivity between the superior parietal gyrus and inferior frontal gyrus was increased after this combined treatment.We speculate that psychodrama enhances the internal connectivity of the cognitive control network and corrects the negative attention bias of patients with childhood trauma-associated MDD.Elucidating the neurobiological features of patients with childhood trauma-associated MDD is important for the development of methods that can assist in early diagnosis and intervention.