Original Title: Terapia electroconvulsiva en depresión grave o resistente al tratamiento

Authors' objectives: The overall objective of this HTA report is to assess the effectiveness, safety and cost-effectiveness, as well as the ethical, legal, organisational, social and environmental aspects associated with the use of ECT in adults with TRD, with the aim of providing scientific evidence to support healthcare decision-making and contribute to the efficient allocation of available resources. To address the overall objective, the following specific objectives were defined: • Assess the effectiveness and safety of ECT in adults with severe depression or treatment-resistant depression. • Assess the cost-effectiveness of ECT in adults with severe depression or treatment-resistant depression. • Identify the ethical, legal, organisational, social and environmental considerations associated with the use of ECT. • Formulate a recommendation on the use of the technology within the NHS, based on the findings from the previous objectives. • Identify future research needs and standard outcome measures related to ECT, from the perspectives of patients, family members/caregivers, health professionals and researchers, regarding the use of ECT in adults with severe depression or TRD.

Authors' results and conclusions: --- RESULTS --- EFFECTIVENESS AND SAFETY [ECT versus rTMS] In the comparison between ECT and rTMS, the report results show that ECT is associated with a greater reduction in depressive symptoms and a higher probability of achieving remission at the end of treatment, both when symptoms are assessed by clinical interview and by self-report, particularly in samples with unipolar depression. By contrast, results for treatment response, commonly defined as a ≥50% reduction in the HDRS, are more variable and do not allow definitive conclusions. Evidence for other clinically relevant outcomes, such as suicidal behaviour or health-related quality of life, is scarce and does not support firm conclusions for this comparison. [ECT versus ketamine] In the comparison between ECT and ketamine, the report results show no statistically significant differences between interventions in any of the main effectiveness outcomes assessed during the acute treatment of the depressive episode. Regarding depressive symptom severity, both clinical interview-based and self-report assessments show significant improvements in both groups, without conclusive differences between ECT and ketamine at the end of treatment. Likewise, remission and response rates, assessed both by interview and by self-report, do not differ significantly between interventions, with imprecise estimates and high heterogeneity in several analyses. [ECT versus esketamine] No studies were identified that directly compared ECT with esketamine in terms of effectiveness and safety. There is a need for pragmatic comparative studies to evaluate these outcomes under real-world clinical practice conditions, particularly in TRD. [ECT versus pharmacotherapy] When ECT is used as monotherapy, the meta-analyses show no statistically significant differences versus pharmacotherapy in depressive symptom severity assessed by clinical interview at the end of treatment. However, the narrative synthesis of individual studies that could not be included in the meta-analyses shows, in most cases, an effect direction favouring ECT over pharmacotherapy, either in terms of greater symptom reduction or earlier improvement in initial phases of treatment. Remission and response rates assessed by clinical interview did not differ significantly between ECT and pharmacotherapy, and available relapse data indicate that, after remission achieved with an acute ECT course, continuation ECT offers no clear advantage over well-structured pharmacological strategies for relapse prevention. [ECT plus pharmacotherapy (augmentation) versus pharmacotherapy alone] In studies evaluating ECT as augmentation added to pharmacotherapy, results show that adding ECT is not associated with an additional reduction in depressive symptom severity during acute treatment compared with pharmacotherapy alone. Meta-analyses identified no statistically significant between-group differences on clinical depression scales, with high heterogeneity, suggesting comparable effectiveness in symptom improvement at the end of the intervention period. However, in the continuation phase after symptom remission, available evidence suggests that the combination of ECT and pharmacotherapy is associated with a significant reduction in relapse risk compared with pharmacotherapy alone. [ECT versus magnetic seizure therapy] A limited number of studies compared ECT with magnetic seizure therapy in the acute treatment of major depressive episodes, mainly in small samples of people with treatment-resistant depression. Overall, results suggest that magnetic seizure therapy may have similar effectiveness to ECT in the acute treatment of treatment-resistant depressive episodes, at least in terms of reduction in depressive symptoms. [ECT versus psychotherapy] Comparative evidence between ECT and psychotherapy comes from a single RCT evaluating continuation strategies following an initial response to an acute course of ECT in people with major depressive disorder. In this study, all participants received continuation pharmacotherapy and were assigned to continuation ECT or continuation group CBT. Results showed that group CBT was associated with significantly higher sustained response rates and lower relapse risk at 6 and 12 months compared with continuation ECT. Continuation ECT showed no advantage over CBT at any of the time points assessed. The available evidence is limited and does not allow firm conclusions to be drawn regarding the comparative superiority of one continuation strategy over another. COST-EFFECTIVENESS The review of economic evaluations identified eight full economic evaluations conducted in OECD countries assessing ECT. The available economic evidence is scarce and heterogeneous, limiting the ability to draw firm conclusions. Studies were grouped into three main comparisons: ECT versus rTMS, ECT versus pharmacotherapy/psychotherapy, and ECT versus esketamine. In the comparison with rTMS, results were inconsistent both in terms of costs and cost-effectiveness, with some studies considering ECT dominant and others finding it dominated. The only economic evaluation conducted in Spain concluded that ECT is a dominant strategy versus rTMS from the perspective of the National Health System. Regarding pharmacotherapy and psychotherapy, evidence is limited to a single study, which indicated that ECT is more costly than these alternatives when used as first-line treatment, but cost-effective when used as a third-line treatment after previous failures. Compared with intranasal esketamine, the only available study showed favourable results for ECT in the acute phase, being highly cost-effective and dominant from a societal perspective. However, when ECT is considered as maintenance therapy, it is more effective but also more costly, with cost-effectiveness ratios close to or slightly above commonly accepted thresholds. COST ANALYSIS The cost analysis showed that the cost of acute treatment with ECT, based on two sessions per week for six weeks, is €13,356.96 per patient, with a range between €10,549.32 and €16,213.39. For rTMS, based on five sessions per week for six weeks, the cost is €3,375.00 per patient, with a range between €2,000.00 and €4,375.00. For intranasal esketamine, based on two sessions per week for four weeks, the cost is €4,912.81 per patient, with a range between €2,017.32 and €5,814.92. ETHICAL, LEGAL, ORGANIZATIONAL, SOCIAL AND ENVIRONMENTAL ASPECTS RESEARCH NEEDS AND STANDARD OUTCOME MEASURES Qualitative evidence shows that the acceptability of ECT is highly contextual and is shaped by the severity of prior suffering and the perception that other therapeutic alternatives have been exhausted. From the perspective of patients and family members, ECT is often accepted as a last-resort option, with low initial acceptability influenced by fear, stigma, and limited health literacy. In this context, the informed consent process emerges as a critical element, as it is frequently described as insufficient, difficult to understand, or constrained by clinical urgency, which hinders fully informed decision-making. Acceptability increases with clinical improvement and when individuals feel listened to and supported by professionals, particularly when the information and consent process is clear, ongoing, and tailored, and decreases in the presence of persistent cognitive effects or experiences perceived as iatrogenic harm. Among healthcare professionals, particularly psychiatrists, acceptability is generally high when there is a clear clinical indication, whereas among nursing staff it is more ambivalent and depends on experience, training, and perceived ethical dilemmas, including tensions related to respect for autonomy and the decision-making capacity of individuals with severe depression. The feasibility of ECT is closely linked to organisational factors, the availability of specialised teams, and staff training. The role of nursing staff is central to procedural safety, patient support, and communication with patients and families, and the lack of standardised protocols for cognitive assessment, follow-up, and the consent process itself constitutes a relevant barrier. In addition, implementation requires continuity of care and complex logistics, which may limit its use in resource-constrained settings. In terms of equity, the evidence suggests geographical and structural inequalities in access to ECT, as well as additional barriers related to social support and health literacy, which directly influence the ability to participate meaningfully in informed decision-making. IDENTIFICATION OF RESEARCH NEEDS AND STANDARD OUTCOME MEASURES The main research needs focus on improving the design of future ECT studies, including adequately powered trials, medium- and long-term follow-up, and assessment of clinically relevant subgroups. The need for systematic and prolonged collection of safety data—especially regarding cognitive effects—is emphasised, as is the generation of primary clinical evidence to enable cost-effectiveness evaluations comparable within the NHS context. Important evidence gaps remain regarding direct comparison with esketamine and the role of ECT as continuation or augmentation therapy. From an organisational and social perspective, there is a need for qualitative research and organisational evaluations to support equitable and acceptable implementation. Through the James Lind Alliance initiative, priorities were identified related to access to depression treatments, the quality of information provided, and the identification of effective interventions in contexts of treatment-resistant depression. No ECT-specific standard outcome sets were identified in COMET or ICHOM; however, systematic use of validated depression symptom scales is recommended, along with relevant outcomes such as quality of life, suicidal ideation, adverse events, functioning and resource use. CONCLUSIONS • Compared with rTMS, ECT was associated with a greater reduction in depressive symptoms and higher remission rates at the end of treatment, particularly in people with unipolar depression. However, results for treatment response were variable and did not allow definitive conclusions. The overall certainty of the evidence for this comparison was rated as very low, mainly due to risk of bias, heterogeneity and imprecision of estimates. • In the comparison between ECT and ketamine, no statistically significant differences were observed in the main effectiveness outcomes assessed. Both depressive symptom severity and response and remission rates improved in both groups, with imprecise estimates and high heterogeneity. The certainty of the evidence for this comparison was considered very low. • When ECT was compared with pharmacotherapy as monotherapy for the depressive episode, meta-analyses showed no statistically significant differences in depressive symptom severity at the end of treatment. However, narrative synthesis of individual studies generally favoured ECT, particularly in terms of earlier symptom improvement. Response and remission rates did not differ significantly between interventions, and relapse data showed no clear advantage of continuation ECT over well-structured pharmacological strategies. The certainty of the evidence for this comparison was considered very low. • In studies evaluating ECT as augmentation added to pharmacotherapy, no additional benefits were identified in reducing depressive symptom severity during acute treatment compared with pharmacotherapy alone. However, in the continuation phase after remission, the combination of ECT and pharmacotherapy was associated with a reduced relapse risk versus pharmacotherapy alone. The certainty of the evidence for this comparison was considered very low. • The heterogeneity observed among the included studies may be influenced not only by inconsistency in the results, but also by variability in the technical implementation of ECT (e.g., electrode placement, stimulation parameters, dose relative to seizure threshold, or type of anesthesia), as well as by differences in the clinical characteristics of the study populations. These factors may contribute to variability in the results and should be considered when interpreting the available evidence and when designing future studies. • ECT showed an overall acceptable safety profile in the included trials. Serious adverse events were infrequent and generally not considered directly attributable to the procedure. However, adverse event assessment and reporting were heterogeneous across studies, limiting comparability. • Regarding cognitive safety, available evidence indicates that ECT is mainly associated with retrograde autobiographical memory disturbances, although the magnitude and persistence of these effects depend on multiple factors, including technical parameters such as electrode placement, dose relative to seizure threshold, and pulse width. These effects are not systematically assessed in trials, and commonly used instruments are not sensitive to the most affected cognitive domains. The lack of medium- and long-term follow-up limits full characterisation of the temporal profile of these effects. • The cost analysis conducted in this report, from the NHS perspective, showed that for complete acute treatment in patients with major depression and treatment resistance, average per-patient costs would be €13,356.96 for ECT, €3,375.00 for rTMS, and €4,912.81 for intranasal esketamine, not including investment in equipment, hospitalisation, or continuation/maintenance treatment. • The acceptability of ECT is highly contextual and cannot be assessed solely in terms of clinical efficacy. Qualitative evidence shows that acceptance among professionals and patients is influenced by stigma, lived experience, the quality of consent and the organisational context. • The informed consent process for ECT presents relevant limitations, particularly in people with severe depression, women and patients with impaired decision-making capacity, posing substantial ethical challenges for responsible implementation. • Implementation and equitable access to ECT depend not only on clinical criteria but also, among other factors, on organisational and social determinants such as the availability of specialised services, specific training of all staff involved, professional attitudes, and support from family members and caregivers. These elements decisively influence who can receive ECT, under what conditions and with what experience, and should be considered comprehensively in planning and organising mental health services.

Authors' recommendations: [ ECT versus rTMS ] According to the results of this report, in adults with severe depression or treatment-resistant depression, a conditional recommendation in favour of ECT versus rTMS is suggested. [ ECT versus ketamine ] According to the results of this report, in adults with severe depression or treatment-resistant depression, a conditional recommendation is suggested for the use of either ECT or ketamine, without clearly favouring either intervention. [ ECT versus pharmacotherapy ] According to the results of this report, in adults with severe depression or treatment-resistant depression, a conditional recommendation is suggested for the use of either ECT or pharmacotherapy. [ ECT plus pharmacotherapy versus pharmacotherapy alone ] According to the results of this report, in adults with severe depression or treatment-resistant depression, a conditional recommendation in favour of ECT in combination with pharmacotherapy is suggested.

Authors' methods: EFFECTIVENESS AND SAFETY A systematic review (SR) of the clinical effectiveness and safety of electroconvulsive therapy (ECT) in adults with severe depression or treatment-resistant depression was conducted, following Cochrane methodology and PRISMA 2020 guidelines. As a preliminary step, a search for HTA reports and reviews was carried out in INAHTA, BRISA, NICE and TRIP, assessing methodological quality using the AMSTAR-2 tool. Randomised controlled trials (RCTs) conducted in adults (≥18 years) were included, evaluating ECT as monotherapy or as an adjunct to pharmacotherapy, compared mainly with repetitive transcranial magnetic stimulation (rTMS), ketamine or esketamine, and pharmacological strategies (including augmentation), as well as magnetic seizure therapy or psychotherapy. Comparisons with placebo or no intervention were excluded. Outcomes included severity of depressive symptoms, response and remission, suicidal ideation and attempts, relapse, health-related quality of life, and adverse events, including cognitive effects. Bibliographic searches were conducted in MEDLINE, Embase, CENTRAL, CINAHL and PsycINFO (July 2025), complemented by manual searching, consultation of ICTRP and BVS, and an alert system in Embase. Reference management was performed using Covidence and Zotero. Two reviewers independently performed study selection, data extraction and risk-of-bias assessment (RoB 2.0), resolving disagreements by consensus or involving a third reviewer. Where feasible, meta-analyses were conducted using RevMan, assessing statistical heterogeneity and planning sensitivity and subgroup analyses. The certainty of the evidence and the formulation of recommendations followed the GRADE methodology. COST-EFFECTIVENESS A systematic review of economic evaluations of ECT in adults with severe or treatment-resistant depression was conducted. Full economic evaluations were included and, specifically, partial evaluations conducted in Spain, restricting inclusion to studies from OECD countries published in English or Spanish. Searches were conducted in MEDLINE, Embase, CEA Registry (Tufts) and EconLit (July 2025), using the economic filter from the Centre for Reviews and Dissemination. Study selection and full-text assessment were performed by two reviewers (an economist and a second reviewer for verification), resolving disagreements by consensus or with support from a third person. Methodological quality was assessed using Drummond’s criteria, and the Spanish study identified was additionally appraised for relevance and transferability using tools specific to the Spanish context. Results were synthesised narratively, updating costs to 2024 euros for Spain. COST ANALYSIS A partial economic evaluation based on a cost analysis was conducted, estimating the average costs associated with the complete acute treatment course with ECT, rTMS and intranasal esketamine in patients with major depression and treatment resistance. The analysis was conducted from the NHS perspective, with a time horizon corresponding to the acute phase of treatment (4–6 weeks). Only direct healthcare costs were included, expressed in 2025 euros, with no discount rate applied. Uncertainty was assessed by estimating, in addition to mean values, minimum and maximum values for each comparator. ETHICAL, LEGAL, ORGANIZATIONAL, SOCIAL AND ENVIRONMENTAL ASPECTS For the analysis of ethical, legal, organisational, social and environmental (ELOSA) domains, the report-specific algorithm was applied, with an initial scoping definition based on a hermeneutic and iterative approach supported by the HTA Core Model 3.0, the GRADE Evidence to Decision framework and the VALIDATE framework. Following this exploratory phase, a systematic review of qualitative evidence was conducted. Questions focused on equity, acceptability and feasibility/implementation. Qualitative and mixed-methods studies with clearly separated qualitative findings were included, conducted in adults and published in English or Spanish within the last 20 years. Searches were conducted in MEDLINE, Embase, CINAHL, PsycINFO and Web of Science (August 2025), complemented by manual searching. Study selection and data extraction were performed by two reviewers; methodological quality was assessed using the CASPe tool; and findings were analysed using thematic coding in Nvivo, organised around the protocol questions. IDENTIFICATION OF RESEARCH NEEDS AND STANDARD OUTCOME MEASURES Areas of uncertainty and outcome measures needed to evaluate the use of ECT in adults with severe or treatment-resistant depression were identified, considering the perspectives of patients and family members, health professionals, researchers and managers. To this end, research needs identified across the systematic reviews undertaken in the different domains of the report were analysed, and specialised sources such as the James Lind Alliance (JLA), Core Outcome Measures in Effectiveness Trials (COMET) and the International Consortium for Health Outcomes Measurement (ICHOM) were reviewed. The selection included publications in English and Spanish, excluding conference abstracts and texts in other languages. Data were extracted by one reviewer and validated by a second reviewer in case of doubts. Findings were synthesised narratively, highlighting the main research needs and key outcome measures to improve comparability and clinical relevance in future ECT studies.

Project Status: Completed

Year Published: 2026

URL for published report: https://sescs.es/en/sescs-report-ect-depression-2025/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Spain

Organisation Name: Canary Health Service

Contact Address: Dirección del Servicio. Servicio Canario de la Salud, Camino Candelaria 44, 1ª planta, 38109 El Rosario, Santa Cruz de Tenerife

Contact Name: sescs@sescs.es

Contact Email: sescs@sescs.es