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Meta-Analysis
. 2019 Mar 19;3(3):CD011847.
doi: 10.1002/14651858.CD011847.pub2.

Electroconvulsive therapy for treatment-resistant schizophrenia

Diarmid Jm Sinclair  1 , Sai Zhao, Fang Qi, Kazare Nyakyoma, Joey Sw Kwong, Clive E Adams
Affiliations
Meta-Analysis

Electroconvulsive therapy for treatment-resistant schizophrenia

Diarmid Jm Sinclair et al. Cochrane Database Syst Rev. .

Abstract

Background: Electroconvulsive therapy (ECT) involves the induction of a seizure by the administration of an electrical stimulus via electrodes usually placed bilaterally on the scalp and was introduced as a treatment for schizophrenia in 1938. However, ECT is a controversial treatment with concerns about long-term side effects such a memory loss. Therefore, it is important to determine its clinical efficacy and safety for people with schizophrenia who are not responding to their treatment.

Objectives: Our primary objective was to assess the effects (benefits and harms) of ECT for people with treatment-resistant schizophrenia.Our secondary objectives were to determine whether ECT produces a differential response in people: who are treated with unilateral compared to bilateral ECT; who have had a long (more than 12 sessions) or a short course of ECT; who are given continuation or maintenance ECT; who are diagnosed with well-defined treatment-resistant schizophrenia as opposed to less rigorously defined treatment-resistant schizophrenia (who would be expected to have a greater affective component to their illness).

Search methods: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including clinical trial registries on 9 September 2015 and 4 August 2017. There were no limitations on language, date, document type, or publication status for the inclusion of records in the register. We also inspected references of all the included records to identify further relevant studies.

Selection criteria: Randomised controlled trials investigating the effects of ECT in people with treatment-resistant schizophrenia.

Data collection and analysis: Two review authors independently extracted data. For binary outcomes, we calculated the risk ratio (RR) and its 95% confidence intervals (CIs), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between the groups and its 95% CIs. We employed the fixed-effect model for all analyses. We assessed risk of bias for the included studies and created 'Summary of findings' tables using the GRADE framework.

Main results: We included 15 studies involving 1285 participants (1264 completers with an average age of 18 to 46 years) with treatment-resistant schizophrenia. We rated most studies (14/15, 93.3%) as at high risk of bias due to issues related to the blinding of participants and personnel. Our main outcomes of interest were: (i) clinically important response to treatment; (ii) clinically important change in cognitive functioning; (iii) leaving the study early; (iv) clinically important change in general mental state; (v) clinically important change in general functioning; (vi) number hospitalised; and (vii) death. No trial reported data on death.The included trials reported useable data for four comparisons: ECT plus standard care compared with sham-ECT added to standard care; ECT plus standard care compared with antipsychotic added to standard care; ECT plus standard care compared with standard care; and ECT alone compared with antipsychotic alone.For the comparison ECT plus standard care versus sham-ECT plus standard care, only average endpoint BPRS (Brief Psychiatric Rating Scale) scores from one study were available for mental state; no clear difference between groups was observed (short term; MD 3.60, 95% CI -3.69 to 10.89; participants = 25; studies = 1; very low-quality evidence). One study reported data for service use, measured as number readmitted; there was a clear difference favouring the ECT group (short term; RR 0.29, 95% CI 0.10 to 0.85; participants = 25; studies = 1; low-quality evidence).When ECT plus standard care was compared with antipsychotics (clozapine) plus standard care, data from one study showed no clear difference for clinically important response to treatment (medium term; RR 1.23, 95% CI 0.95 to 1.58; participants = 162; studies = 1; low-quality evidence). Clinically important change in mental state data were not available, but average endpoint BPRS scores were reported. A positive effect for the ECT group was found (short-term BPRS; MD -5.20, 95% CI -7.93 to -2.47; participants = 162; studies = 1; very low-quality evidence).When ECT plus standard care was compared with standard care, more participants in the ECT group had a clinically important response (medium term; RR 2.06, 95% CI 1.75 to 2.42; participants = 819; studies = 9; moderate-quality evidence). Data on clinically important change in cognitive functioning were not available, but data for memory deterioration were reported. Results showed that adding ECT to standard care may increase the risk of memory deterioration (short term; RR 27.00, 95% CI 1.67 to 437.68; participants = 72; studies = 1; very low-quality evidence). There were no clear differences between groups in satisfaction and acceptability of treatment, measured as leaving the study early (medium term; RR 1.18, 95% CI 0.38 to 3.63; participants = 354; studies = 3; very low-quality evidence). Only average endpoint scale scores were available for mental state (BPRS) and general functioning (Global Assessment of Functioning). There were clear differences in scores, favouring ECT group for mental state (medium term; MD -11.18, 95% CI -12.61 to -9.76; participants = 345; studies = 2; low-quality evidence) and general functioning (medium term; MD 10.66, 95% CI 6.98 to 14.34; participants = 97; studies = 2; very low-quality evidence).For the comparison ECT alone versus antipsychotics (flupenthixol) alone, only average endpoint scale scores were available for mental state and general functioning. Mental state scores were similar between groups (medium-term BPRS; MD -0.93, 95% CI -6.95 to 5.09; participants = 30; studies = 1; very low-quality evidence); general functioning scores were also similar between groups (medium-term Global Assessment of Functioning; MD -0.66, 95% CI -3.60 to 2.28; participants = 30; studies = 1; very low-quality evidence).

Authors' conclusions: Moderate-quality evidence indicates that relative to standard care, ECT has a positive effect on medium-term clinical response for people with treatment-resistant schizophrenia. However, there is no clear and convincing advantage or disadvantage for adding ECT to standard care for other outcomes. The available evidence was also too weak to indicate whether adding ECT to standard care is superior or inferior to adding sham-ECT or other antipsychotics to standard care, and there was insufficient evidence to support or refute the use of ECT alone. More good-quality evidence is needed before firm conclusions can be made.

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Conflict of interest statement

Diarmid Sinclair: none known.

Sai Zhao: none known.

Fang Qi: none known.

Kazare Nyakyoma: none known.

Joey Kwong: none known.

Clive Adams: none known.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 ECT plus standard care versus sham‐ECT plus standard care, Outcome 1 Mental state ‐ total score (BPRS, high = poor) ‐ short term.
1.2
1.2. Analysis
Comparison 1 ECT plus standard care versus sham‐ECT plus standard care, Outcome 2 Service use ‐ number readmitted ‐ short term.
2.1
2.1. Analysis
Comparison 2 ECT plus standard care versus antipsychotics plus standard care, Outcome 1 Response to treatment ‐ clinically important response (BPRS reducing rate ≥ 50%) ‐ medium term.
2.2
2.2. Analysis
Comparison 2 ECT plus standard care versus antipsychotics plus standard care, Outcome 2 Mental state ‐ total score (BPRS, high = poor) ‐ short term.
2.4
2.4. Analysis
Comparison 2 ECT plus standard care versus antipsychotics plus standard care, Outcome 4 Mental state ‐ specific symptom score (BPRS, high = poor) ‐ short term.
2.5
2.5. Analysis
Comparison 2 ECT plus standard care versus antipsychotics plus standard care, Outcome 5 Mental state ‐ specific symptom score (BPRS, high = poor) ‐ medium term.
2.6
2.6. Analysis
Comparison 2 ECT plus standard care versus antipsychotics plus standard care, Outcome 6 Adverse events ‐ total score (TESS, high = poor).
3.1
3.1. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 1 Response to treatment ‐ clinically important response (as defined by each study).
3.2
3.2. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 2 Cognitive functioning ‐ memory deterioration ‐ short term.
3.3
3.3. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 3 Cognitive functioning ‐ specific symptom score (WCST, high = poor, other than correct number) ‐ medium term.
3.5
3.5. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 5 Cognitive functioning ‐ memory (WMS, high = good) ‐ short term.
3.6
3.6. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 6 Cognitive functioning ‐ memory (WMS, high = good) ‐ medium term.
3.7
3.7. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 7 Satisfaction and acceptability of treatment ‐ leaving the study early ‐ medium term.
3.8
3.8. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 8 Mental state ‐ total score (BPRS, high = poor).
3.10
3.10. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 10 Mental state ‐ total score (MMSE, high = good) ‐ medium term.
3.11
3.11. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 11 Mental state ‐ total score (PANSS, high = poor).
3.12
3.12. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 12 Mental state ‐ specific symptom score (BPRS, high = poor) ‐ short term.
3.13
3.13. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 13 Mental state ‐ specific symptom score (BPRS, high = poor) ‐ medium term.
3.14
3.14. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 14 Mental state ‐ specific symptom score (PANSS, high = poor) ‐ short term.
3.16
3.16. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 16 Mental state ‐ specific symptom score (PANSS, high = poor) ‐ medium term.
3.18
3.18. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 18 Mental state ‐ specific symptom score (SAPS, high = poor) ‐ short term.
3.19
3.19. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 19 Mental state ‐ specific symptom score (SANS, high = poor) ‐ short term.
3.20
3.20. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 20 General functioning ‐ total score (GAF, high = good).
3.21
3.21. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 21 Adverse events ‐ general ‐ medium term.
3.22
3.22. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 22 Adverse events ‐ total score (TESS, high = poor).
3.23
3.23. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 23 Adverse events ‐ specific symptom ‐ short term.
3.24
3.24. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 24 Adverse events ‐ specific symptom ‐ medium term.
3.26
3.26. Analysis
Comparison 3 ECT plus standard care versus standard care, Outcome 26 Adverse events ‐ specific symptom score (TESS, high = poor) ‐ medium term.
4.1
4.1. Analysis
Comparison 4 ECT alone versus antipsychotic alone (flupenthixol), Outcome 1 Mental state ‐ total score (BPRS, high = poor) ‐ medium term.
4.2
4.2. Analysis
Comparison 4 ECT alone versus antipsychotic alone (flupenthixol), Outcome 2 Mental state ‐ total score (MMSE, high = good) ‐ medium term.
4.3
4.3. Analysis
Comparison 4 ECT alone versus antipsychotic alone (flupenthixol), Outcome 3 General functioning ‐ total score (GAF, high = good) ‐ medium term.
5.1
5.1. Analysis
Comparison 5 SUBGROUP: ECT plus standard care versus standard care (TEST FOR DIFFERENCE BETWEEN SHORT/LONG COURSE OF ECT), Outcome 1 Response to treatment ‐ clinically significant response (as defined by each study) ‐ medium term.
6.1
6.1. Analysis
Comparison 6 SENSITIVITY ANALYSIS: ECT plus standard care versus standard care (ASSUMPTIONS FOR LOST BINARY DATA), Outcome 1 Response to treatment ‐ clinically significant response (as defined by each study) ‐ medium term.
7.1
7.1. Analysis
Comparison 7 SENSITIVITY ANALYSIS: ECT plus standard care versus standard care (FIXED‐EFFECT AND RANDOM‐EFFECTS MODEL), Outcome 1 Response to treatment ‐ clinically significant response (as defined by each study) ‐ medium term.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD011847

References

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References to studies awaiting assessment

Chen 2006 {published data only}
    1. Chen M. Observation and nursing of multi‐parameter monitoring electroconvulsive therapy for schizophrenia [多参数监护电休克治疗精神分裂症的疗效观察及护理]. 中国现代临床护理学杂志 [Journal of Chinese Modern Clinical Nursing] 2006; Vol. 1, issue 5:433.
Melzer 2015 {published data only}
    1. Melzer‐Ribeiro DL, Rigonatti SP, Kayo M, Ribeiro RB, Avrichir B, Fortes M, et al. Pilot double blind, placebo controlled and randomized study to assess electroconvulsive therapy efficacy as augmenting strategy to clozapine in super‐refractory schizophrenia. Schizophrenia Bulletin 2015;41:S323‐4.
    1. NCT02049021. Electroconvulsive therapy (ECT) in patients with super refractory schizophrenia [Pilot double blind, placebo controlled and randomized study to assess electroconvulsive therapy efficacy as augmenting strategy to clozapine in super‐refractory schizophrenia]. clinicaltrials.gov/show/NCT02049021 (first received 15 January 2014).
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References to ongoing studies

NCT00042224 {published data only}
    1. NCT00042224. ECT in clozapine refractory schizophrenia. www.clinicaltrials.gov/ct/show/NCT00042224 (first received 24 July 2002).
NCT00753051 {published data only}
    1. NCT00753051. Treat clozapine‐resistant schizophrenia comparing between clozapine + haloperidol versus clozapine + electroconvulsive therapy (ECT). www.clinicaltrials.gov/ct/show/NCT00753051 (first received 15 September 2008).
NCT02926976 {published data only}
    1. NCT02926976. The optimal treatment for treatment‐resistant schizophrenia. www.clinicaltrials.gov/show/NCT02926976 (first received 5 October 2016).

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