Electroconvulsive Therapy Added to Non-Clozapine Antipsychotic Medication for Treatment Resistant Schizophrenia: Meta-Analysis of Randomized Controlled Trials

Zheng, Wei; Cao, Xiao−Lan; Ungvári, Gábor S.; Xiang, Yong; Guo, Tong; Liu, Zhengrong; Wang, Yuanyuan; Forester, Brent P.; Seiner, Stephen J.; Xiang, Yu‐Tao

doi:10.1371/journal.pone.0156510

Cited by 51 publications

(33 citation statements)

References 36 publications

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“…Since three points on the ATHF represents a single adequate treatment trial that has failed, this patient had failed or could not tolerate numerous antipsychotic medications—including clozapine. A recent meta-analysis of RCTs that examined the combination of ECT with non-clozapine antipsychotics found a response rate of 50.9% compared to 32.9% in non-clozapine antipsychotic monotherapy ( 33 ). For patients who are clozapine-resistant, a recent meta-analysis of four open-label clinical trials and one randomized single blinded RCT in patients inadequately responding to clozapine reported a pooled response proportion of 54% with combination treatment of clozapine and ECT treatment ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Magnetic Seizure Therapy in Treatment-Resistant Schizophrenia: A Pilot Study

et al. 2018

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ObjectiveElectroconvulsive therapy is effective in treatment-resistant schizophrenia (TRS) but use is limited due to stigma and concerns around cognitive adverse effects. Magnetic seizure therapy (MST) is a promising new neuromodulation technique that uses transcranial magnetic stimulation to induce therapeutic seizures. Studies of MST in depression have shown clinical improvement with a favorable adverse effect profile. No studies have examined the clinical utility of MST in schizophrenia.MethodsWe conducted an open-label pilot clinical trial of MST in eight TRS patients. Up to 24 MST treatments were delivered depending on treatment response. We assessed clinical outcome through the Brief Psychiatric Rating Scale (BPRS) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Cognitive testing included a neuropsychological test battery, the Autobiographical Memory Inventory (AMI), Montreal Cognitive Assessment (MoCA), and reorientation time.ResultsFour patients completed the trial as per protocol. For all patients and for trial completers alone, there was a significant clinical and quality of life improvement. Three met pre-determined criteria for remission (total score ≤25 on the BPRS) and one met criteria for response (i.e., ≥25% BPRS improvement from baseline for two consecutive assessments). Pre and post neurocognitive data showed no significant cognitive adverse effects apart from a decrease in AMI scores.ConclusionIn this pilot study, MST demonstrated evidence for feasibility in patients with TRS, with promise for clinical efficacy and negligible cognitive side effects. Further study in larger clinical populations is needed.Clinical Trial Registration, Identifier NCT01596608.

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Section: Discussionmentioning

confidence: 99%

Magnetic Seizure Therapy in Treatment-Resistant Schizophrenia: A Pilot Study

et al. 2018

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“…Another study also reported that patients with ECT treatment developed seizures [33] . Still another study reported a higher incidence of a headache and memory impairment in subjects who received ECT [14] .…”

Section: Resultsmentioning

confidence: 93%

“…It was also seen that, among the non-clozapine groups, flupenthixol was most frequently used, and was found to be the most efficient in relieving treatment-resistant schizophrenia, when augmented with ECT. Previous analyses and studies [ 14 , 54 ] have focused on the comparison of treatment and control groups, with respect to a specific drug class, and this has led to the ignorance and exclusion of other important information generated by the open trials. Hence, the comparison of the results produced by these other studies, directed towards relieving the symptoms of treatment-resistant schizophrenia as researched in this present study, not only identified the superior drug for treatment, but also allowed identification of the most effective drug within the different classes.…”

Section: Discussionmentioning

confidence: 99%

“…Existing literature on the treatment of schizophrenia offers ample insights into the efficacy of augmentation therapies [ 11 , 14 ] but the relative analysis between the efficacies of different ECT-drug combinations have not been investigated into in much detail. While the current practice is to use clozapine unless contraindicated due to its gold standard status for psycho-active treatment alone, augmented therapy may differ in results.…”

Section: Introductionmentioning

confidence: 99%

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Combined use of electroconvulsive therapy and antipsychotics (both clozapine and non-clozapine) in treatment resistant schizophrenia: A comparative meta-analysis

Ahmed

Khan

Mekala³

et al. 2017

Heliyon

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AimTo assess the relative efficacies of clozapine plus Electroconvulsive Therapy (ECT) compared against non-clozapine typical and atypical antipsychotics plus ECT for the treatment of “Treatment Resistant Schizophrenia” (TRS). Primarily to assess if clozapine delivers a significant improvement over other antipsychotics when combined with ECT.DesignMajor electronic databases were searched between 1990 and March 2017 for trials measuring the effects of either clozapine augmented ECT, other antipsychotic-augmented ECT, or both. After the systematic review of the data, a random-effects meta-analysis was conducted measuring the relative effect sizes of the different treatment regimens.Subjects1179 patients in 23 studies reporting the usage of ECT augmentation with antipsychotics. A total of 95 patients were tested with clozapine, and ECT (9 studies) and 1084 patients were tested with non-clozapine antipsychotics (14 studies) such as flupenthixol, chlorpromazine, risperidone, sulpiride, olanzapine, and loxapine with concurrent ECT treatment considered for systematic review. Of these, 13 studies reported pre and post-treatment scores were included in the meta-analysis.Main outcome measuresThe main outcome measure was the presence and degree of both positive and negative psychotic symptoms, as measured by either of two standardized clinician administered tests, the Brief Psychiatric Rating Scale (BPRS), and the Positive and Negative Symptom Scale (PANSS).ResultsThe comparison of the different antipsychotics established the supremacy of ECT-augmented clozapine treatment against other typical and atypical antipsychotics. The Forest Plot revealed that the overall standard mean difference was 0.891 for non-clozapine studies and 1.504 for clozapine studies, at a 95% interval. Furthermore, the heterogeneity plots showed that while clozapine studies showed no significant heterogeneity, non-clozapine studies showed an I2 statistic value at 42.19%, suggesting moderate heterogeneity. Lastly, publication bias showed asymmetrical plots and significant values of Kendal's tau and Egger's rank test.ConclusionECT augmentation technique was found to be effective in the reduction of psychometric scale scores, and the resulting improvement was significant. Clozapine maintained its stance as the most effective treatment for Treatment-Resistant Schizophrenia, followed by flupenthixol.

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“…[7][8][9][10] Its effectiveness has been supported by 2 recent meta-analyses that demonstrated a significant effect in reducing symptom severity among those who received ECT augmentation of clozapine or nonclozapine antipsychotics. 11,12 Few studies have specifically investigated the effect of ECT augmentation with antipsychotics for schizophrenia on long-term relapse/re-hospitalization rates. One case series that enrolled 11 clozapine-resistant patients with schizophrenia showed that 63% relapsed within months after ECT was discontinued.…”

Section: Introductionmentioning

confidence: 99%