Depression in adults: treatment and management NICE guideline NG222

Several studies have assessed the efficacy of ECT for treatment-resistant depression (TRD), with mixed results when compared to other therapies. 22 relevant studies were identified from our searches on electroconvulsive therapy, monitoring, and relapse prevention in depression.

Electroconvulsive therapy in the treatment of depression

Guo et al. (2024) conducted a network meta-analysis of 72 RCTs (n=12,105) assessing treatments for TRD, confirming that ECT offers lasting benefits for individuals with long-standing depression. However, the study cautioned that its effects may diminish without continued treatment, highlighting the need for ongoing monitoring. Yang et al. (2024) conducted a network meta-analysis (17 RCTs, n=1,370) comparing ketamine and ECT, concluding that ECT was superior in reducing depressive symptoms but carried a higher risk of memory impairment, which may limit its appeal for some patients.

Graeff Saldanha et al. (2024) conducted a systematic review and meta-analysis of 7 RCTs (n=1,250), the findings suggest that both ECT and ketamine were effective, but ECT was superior in achieving remission, while ketamine had a faster onset of action. Saelens et al. (2024) conducted systematic review and network metanalyses of 69 RCTs (n=10,285) on antidepressant treatments for TRD, confirmed that ECT had the highest response rates and fastest symptom improvement compared to other therapies, reinforcing its position as a top treatment. Menon et al. (2023) conducted a meta-analysis (5 RCTs, n=278), reporting that ECT was more effective than ketamine, with better post-treatment ratings, response, and remission rates, although both treatments required a similar number of sessions with no significant differences in cognitive outcomes. Moreira et al. (2023) analysed 8 studies (n=2,875) comparing ketamine and ECT for TRD, finding no significant difference in reducing depressive symptoms or therapy response between the two treatments. However, ketamine had a lower risk of muscle pain, while other side effects like dissociation and nausea were similar for both treatments. Read et al. (2020) reviewed the validity of 11 studies (n=1,430) across 5 meta-analyses comparing ECT to sham ETC, concluding that while ECT reduced depression severity, the overall quality of the studies was low, raising uncertainty about whether ECT is truly superior to sham ECT.

Anand et al. (2023) compared ketamine and ECT (RCT, n=403) and found ketamine to be similarly effective, with 55.4% of patients responding versus 41.2% for ECT. Ketamine caused fewer memory issues, while ECT led to memory decline. Both improved quality of life, though ECT caused musculoskeletal side effects, and ketamine caused dissociation. Rhee et al. (2022) reviewed 6 clinical trials (n=340) comparing ketamine and ECT for major depressive episodes, finding ECT more effective in reducing depression severity. Side effect profiles differed: ketamine caused fewer headaches and muscle pains, while ECT caused fewer vision issues and dissociative symptoms. Jha et al. (2024) conducted a secondary analysis of an RCT (n=365) examining clinical features influencing treatment response to ketamine versus ECT in nonpsychotic TRD, finding that ECT was more effective for moderate to severe depression, though its benefits were less significant for milder forms of depression.

Other studies have explored ECT's broader applications. Bai et al. (2021) studied modified ECT for refractory obsessive-compulsive disorder (OCD) (RCT, n=76), finding it more effective than medication alone, though with increased near-memory impairment. Liu et al. (2024) compared dexmedetomidine (DEX) and ECT (RCT, n=76), finding DEX comparable to ECT in rapid antidepressant effects but with fewer cognitive side effects. Mutz et al. (2019) in a network metanalysis of 113 RCTs (n=6,750) on non-surgical brain stimulation therapies, it suggests ECT as one of the most effective treatments for major depressive episodes, although transcranial magnetic stimulation (repetitive rTMS) had fewer cognitive-related side effects. Pluijms et al. (2021) reviewed 9 studies (RCTs and cohort studies n=550) on adjuvant antidepressants with ECT, showing that combining antidepressants enhanced ECT's effectiveness for major depression.

Long-term efficacy and relapse prevention

The question of long-term efficacy in treating treatment-resistant depression (TRD) with ECT remains debated, particularly regarding relapse prevention in depression and sustained benefits.

Zhou et al. (2021) reviewed 36 RCTs (n=2,100) on non-pharmacological interventions for relapse prevention in treatment resistant depression, highlighting ECT as particularly effective, although psychotherapy was a viable alternative. Brus et al. (2024) conducted a long-term follow-up of a trial comparing maintenance electroconvulsive therapy (M-ECT) with medication alone in depression. They found that M-ECT's benefits were largely maintained over several years, though there is uncertainty due to small sample (n=56), and relapse patterns were similar after M-ECT ended.

Veraart et al. (2021) systematically reviewed 6 studies comparing ketamine and ECT for TRD, concluding that while ketamine produced faster antidepressant effects, ECT showed greater durability. Ketamine also had fewer cognitive side effects, but study quality varied due to risks of bias and small sample sizes. Blanken et al. (2024) conducted a network meta-analysis predicting ECT remission in major depressive disorder based on baseline symptoms. Their analysis across 2 RCTs (n=161) suggests that patients with suicidal ideation may have a worse treatment outcome, while those with psychomotor retardation and hypochondriasis may experience better outcomes with ECT.

Yoldi-Negrete et al. (2022) reviewed 9 studies on maintenance ECT, confirming its effectiveness in preventing relapse, though benefits were marginal compared to ongoing pharmacological treatments. Rowland et al. (2023) analysed 20 studies (RCTs and observational studies n=1,800) on continuation and maintenance ECT, supporting its role in reducing relapse rates without notable cognitive side effects. Further evidence comes from Dar et al. (2023), who reviewed 6 RCTs on ECT for relapse prevention in treatment resistant depression, showing that combining ECT with antidepressants significantly reduced recurrence risk compared to antidepressants alone, though ECT alone showed no significant advantage.

Jelovac et al. (2025) conducted a systematic review and meta-analysis of continuation electroconvulsive therapy combined with pharmacotherapy for depression relapse prevention. The meta-analysis included 4 RCTs (n=254) on adults diagnosed with a unipolar or bipolar major depressive episode, who met remission or response criteria after an acute course of ECT. No information was provided whether the patients in the RCTs were TRD or not. Patients were randomized to ECT with pharmacotherapy versus pharmacotherapy alone. The meta-analysis suggests ECT combined with pharmacotherapy significantly reduced relapse compared to pharmacotherapy alone. The quality of the included studies is mixed, with 2 studies rated as having some concerns and 2 studies rated as having a high risk of bias based on the Cochrane risk of bias tool 2.0. The authors highlight the need for larger multicenter trials to further optimize post-ECT prophylaxis.

Impact of new evidence on NICE guideline NG222 recommendations

Electroconvulsive therapy in the treatment of depression: Recent studies reinforce the effectiveness of ECT in treating treatment-resistant depression (TRD), particularly for relapse prevention in treatment resistant depression and long-term benefits. Guo et al. (2024) and Yoldi-Negrete et al. (2022) confirm that ECT plays a key role in preventing relapse, aligning with NICE guideline NG222 recommendation to consider ECT when other treatments fail or a rapid response is required (Recommendation 1.13.1).

However, studies like Yang et al. (2024) highlight ECT's higher risk of memory impairment despite its effectiveness over ketamine, reinforcing NICE guideline NG222 (recommendation 1.13.2). This stresses the need to fully inform patients about ECT's risks and benefits, including cognitive side effects, anaesthesia risks, medical conditions, and increased risks for older adults.

Further research, such as Graeff Saldanha et al. (2024) and Saelens et al. (2024), highlights ECT's high response rates, supporting its role as an effective last treatment option.

Long-term efficacy and relapse prevention: Jha et al. (2024)'s study also supports NG222's guidance on considering the adequacy of previous ECT courses before deciding on a repeat trial, while Dar et al. (2023) and Jelovac et al. (2025) demonstrate that combining ECT with antidepressants significantly reduces relapse risk, aligning with NG222's recommendation to repeat treatment post-ECT (recommendation 1.13.5) if people have responded well to ECT previously.

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2025 surveillance of electroconvulsive therapy (technology appraisal guidanceTA59, NICE guideline NG222, NICE guideline CG178, NICE guideline CG185, NICE guideline CG192)