Longitudinal Associations of Electroconvulsive Therapy with All-cause Mortality and Suicide Deaths in Depression and Other Psychiatric Disorders: A Systematic Review and Meta-Analysis

Longitudinal Associations of Electroconvulsive Therapy with All-cause Mortality and Suicide Deaths in Depression and Other Psychiatric Disorders: A Systematic Review and Meta-Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Longitudinal Associations of Electroconvulsive Therapy with All-cause Mortality and Suicide Deaths in Depression and Other Psychiatric Disorders: A Systematic Review and Meta-Analysis Taeho Greg Rhee, sungryul shim, Madeeha Nasir, Roger McIntyre, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6180102/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: Electroconvulsive therapy (ECT) is among the most effective treatments for mood disorders and other psychotic disorders. This study meta-analyzed the effects of ECT on all-cause mortality and suicide deaths using longitudinal studies. Methods: PubMed/MEDLINE, PsycINFO, Cochrane Library, Embase, and Google Scholar were searched from inception through January 21, 2025, with no language limits. Inclusion criteria were as follow: (1) patients with diagnoses of mental disorders; (2) intervention consisted of ECT compared with placebo, usual care or another intervention; (3) all-cause mortality and suicide deaths as outcome measures; and (4) clinical trial or longitudinal cohort study designs where the aforementioned interventions preceded the observations of outcome measures. Adjusted hazard ratio [HR] with their corresponding 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. Moderator analyses were also performed. Results: Overall, 17 studies consisting of 1,182,501 individuals (n=40,867 for ECT, n=1,141,634 for those receiving comparable interventions) were included. ECT was associated with a reduction in risk of all-cause mortality (HR, 0.70 [95% CI, 0.61-0.81]; p <0.001), a finding that was consistent at 3 months, 6 months, and 12 months of follow-up. Sex demonstrated a very small moderating effect on this relationship, with ECT being slightly less protective against mortality risk for females compared to males (standardized beta coefficient, -0.01 [-0.01 to 0.00]; p =0.036). Regions also had a moderating effect ( p =0.002). Japan had the largest effect size (HR, 0.17 [0.04-0.72]) and Denmark had the smallest (HR, 0.87 [0.83-0.92]). ECT was associated with a reduction in suicide risk at 3 months of follow-up (HR, 0.53 [0.39-0.72]; p <0.001) but not at 1, 6, or 12 months of follow-up. Conclusions: ECT is associated with a reduced risk of all-cause mortality. ECT, however, was not consistently associated with a reduced risk of suicide. Health sciences/Diseases/Psychiatric disorders/Depression Health sciences/Diseases/Psychiatric disorders/Bipolar disorder depression major depressive disorder electroconvulsive therapy ECT suicide suicide attempt Figures Figure 1 Figure 2 Figure 3 Introduction Mood disorders are a leading cause of disability and mortality. 1 Mood disorders are associated with a dramatically reduced life expectancy, translating to approximately 10 years of lost life expectancy among males and 7–11 years among females. 2 Those who suffer from mood disorders are at an increased risk of suicide when compared to the general population. However, increased rates of mortality among this group are not solely attributable to suicide; risks for deaths due to cardiovascular disease, cancer, and other comorbid medical conditions are also elevated among individuals with mood disorders. 3 – 5 Individuals with schizophrenia spectrum and other psychotic disorders are also at considerably elevated risk of premature mortality (including suicide) compared to the general population. 6 Electroconvulsive therapy (ECT) is among the most effective treatments for mood disorders, 7 and also has efficacy for treatment-resistant psychotic disorders. 8 Prior research suggests that ECT may reduce the risk of suicide as well as all-cause mortality. However, several methodological limitations cast uncertainty over this conclusion. For instance, one early study followed 135 patients who received ECT from a single state psychiatric facility. While this report showed a reduced risk of all-cause mortality, baseline differences between the group receiving ECT and the group that did not receive ECT were not accounted for. 9 Another study from the state of New York reported a higher mortality risk among ECT patients; again, there was no attempt to account for baseline clinical differences between cohorts. 10 Clinical practice standards suggest ECT should be considered for patients with mood disorders at risk of suicide. 11 – 13 However, the evidence of the effects of ECT on suicide deaths have been inconsistent. 14 While some studies suggest a protective effect of ECT against suicide, 15 , 16 other studies report that any protective effect is quite transient. 17 Given the nature of ECT, blinded studies are no longer possible. In addition, as ECT is most commonly given to the most severely ill patients, observational studies that sufficiently account for potential confounding factors are crucial to further elucidating this relationship. In the last few years, a number of high-quality longitudinal studies examining the relationship between ECT, all-cause mortality and suicide using large databases have been published. 17 – 20 In the present study, we conduct a systematic review and meta-analysis that include these recent large and high-quality studies to better clarify the effects of ECT on all-cause mortality and suicide deaths among patients with psychiatric conditions. Methods Search strategy The protocol pertaining to this study was registered on PROSPERO (CRD42025641749). A systematic search was conducted from inception to January 21, 2025. The following databases were systematically searched: PubMed/MEDLINE, PsycINFO, the Cochrane Library, and Embase using Medical Subject Headings (MeSH) terms and text keywords. We also manually searched all relevant studies in GoogleScholar ( https://scholar.google.com/ ). No language restrictions were imposed. Search strategies are provided in Supplementary Table 1 in the Supplement. Two authors (TGR and SRS) independently identified relevant studies among the results of the systematic search. References of included studies were also screened for relevant studies. This study followed the preferred reporting items for meta-analysis of observational studies in epidemiology (MOOSE) reporting guidelines ( Supplementary Table 2 ). 21 Our study used publicly available data and did not include human participant research. As per 45 CFR § 46.102(f), this study was not submitted for institutional review board approval and did not require informed consent procedures. Eligibility criteria and study selection Inclusion criteria were established prior to article reviews and were as follows: (1) patients with a diagnosis of mental disorder using standardized diagnostic criteria (e.g., Diagnostic and Statistical Manual of Mental Disorders, fifth Edition [DSM-5] or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10]); (2) intervention/comparator groups consisted of ECT compared with placebo, usual care, or another intervention; (3) outcome measures of validated all-cause mortality or suicide deaths; and (4) randomized controlled trial or longitudinal cohort study designs where the aforementioned interventions preceded the observations of outcome measures. Exclusion criteria were as follow: (1) non-human studies; (2) no use of standardized measures for mental disorder or primary outcomes of interest; or (3) case-control or anecdotal (e.g., case series, case reports, and editorials) study designs. Within-group comparisons (i.e., when participants were receiving the ECT compared to when they were not) were excluded, as were studies using historical comparisons. Study identification and data extraction Titles and abstracts were independently screened by two reviewers (TGR and SRS), and articles identified as potentially relevant by at least one reviewer were retrieved and duplicates were removed. Full-text articles were independently screened by the same reviewers, and discrepancies were resolved through discussion. Data from included articles were independently extracted by the two reviewers using a pilot-tested data extraction form and then corroborated, with discrepancies resolved through discussion. Information to be extracted was established a priori and included: study characteristics (e.g., PICOTS framework), participant characteristics (e.g., clinical and diagnostic information as well as other co-morbidities), data source, selection of cases and controls, sample size and follow-up period, modes of ascertainment, methods of data analysis (e.g., relative measures using adjusted odds ratio [OR], hazard ratio [HR], or relative risk [RR]), and quantitative data pertaining to any primary and secondary outcomes along with covariates. For observational studies where cohort groups often differed with respect to person-time of exposure, we favored (where available) the use of person-years in the denominator. To ensure the absence of overlapping data and to maintain the integrity of the meta-analysis, data and references for each included study were carefully cross-checked. Assessment methodological quality The risk of bias and methodological quality were evaluated using the Newcastle-Ottawa Scale (NOS) for the assessment of the quality of non-randomized studies in meta-analyses. 22 , 23 We assessed eight items across three domains: selection (adequate definition of case; representativeness of case; definition of control; selection of control); comparability of cases and controls based on the design or analysis; and exposure/outcome (ascertainment of exposure or outcome; same method of ascertainment for cases and controls; and non-response rate). The overall quality was classified as being indicative of a ‘ good quality ,’ ‘ fair quality ,’ or ‘ poor quality .’ 22 , 23 Publication bias We used funnel plots to visually explore for evidence of association between the effect sizes and statistical precision. 24 We supplemented visual assessments with statistical testing of funnel plot asymmetry using Egger’s test (i.e., a weighted linear regression of effect size versus precision) 25 and Begg and Mazumdar’s test (i.e., rank correlation test). 26 Evidence of associations between effect sizes and precision across studies may indicate design heterogeneity, chance or selection biases that operate cross the evidence base (e.g., publication and outcome reporting bias). Statistical analysis The primary outcomes of interest for each comparison were (1) death by any cause (i.e., all-cause mortality) and (2) suicide deaths, assessed as described in each study (either through prospective observation or database analysis [e.g., the Nation Death Index or similar registries]). Where possible, the time over which the outcomes were assessed was standardized across studies (e.g., 3-, 6-, and 12-month follow-up periods). Because different studies reported three types of relative measures (i.e., OR, HR, and RR), we converted adjusted ORs and RRs to HRs. The weight of each study was determined using an inverse-variance method. 24 We used both I -squared statistic and Cochran’s Q -statistic to quantify the proportions of heterogeneity due to within- and between-study variations. 24 To adequately estimate the overall effect sizes, relative measures (e.g., ORs, HRs, or RRs) with their corresponding 95% confidence intervals (CIs) were calculated using fixed- or random-effects models depending on the model assumptions. 24 More specifically, a random-effects model was used when I -squared statistic was > 50% and a fixed-effects model was used when I -squared statistic was < 50%. We reported both random- and fixed-effects models when I -squares statistics was 50%. The Q -statistic was used to assess between-study heterogeneity. This statistic provides a quantitative test indicating whether different effect sizes between studies are attributable to subject-level sampling alone or other sources of variability. We estimated the degree of heterogeneity using the I -squared statistic, which estimates the proportion of total variance attributable to variance between different studies. We also conducted moderator analyses using meta-regression analyses by study sample size; relative risk measure (e.g., OR, HR, and RR); age; female sex (%); diagnosis (including psychotic depression and bipolar depression); and country. When identifying potential moderators, we used the variance of the true effects using a restricted maximum likelihood (REML) estimator. 27 We used a statistical software, R 4.2.1. [R Foundation for Statistical Computing] for all analyses using the “ meta ” package. 28 Finally, as mentioned earlier, we assessed publication bias (or small-study effects) using funnel plots; 24 Egger’s test and Begg and Mazumdar’s test were also performed when assessing the publication bias. 24 Unless otherwise noted, a two-sided p -value < 0.05 was considered for statistically significance. Role of the funding source The funders were not involved in the study design, data collection, analysis, interpretation of data, writing of the report, or the decision to submit the manuscript for publication. RESULTS Characteristics of included studies The literature search yielded 7,530 articles, of which 63 were eligible after screening titles and abstracts and removing duplicates. Of these eligible studies, 54 were further excluded after full-text screening. Two independent investigators (TGR and SRS) discovered 8 additional studies by manually searching reference lists and GoogleScholar (Fig. 1 ). Overall, 17 studies 9,10,15–20,29−39 consisting of 1,182,501 subjects (n = 40,867 for patients receiving ECT and n = 1,141,634 for patients receiving other comparable interventions) were included in the review (Table 1 ). From these studies, 13 effect sizes for all-cause mortality and 12 effect sizes for suicide deaths were identified for meta-analyses. Fourteen of 17 studies (82.4%) were conducted in inpatient settings, and 9 of 17 (52.9%) were conducted in the United States. Almost all studies had patients with unipolar or bipolar depression, except one study 31 that had patients with schizoaffective disorder. Table 1 provides details of study characteristics, including mean age, proportion of female sex and follow-up time, for all included studies. Table 1 Selected characteristics of included studies for both qualitative and quantitative analyses Author and publication year Diagnosis Sample size (ECT) Sample size (control) Inpatient v. outpatient Country Mean age Proportion female Proportion psychotic depression Follow Up Time Huston et al., 1948 29,30 MDD/bipolar depression 74 80 Inpatient USA Varies 56.5% 29.9% 35 months (median) Avery et al., 1978 9 Depression 257 334 Inpatient USA Unknown 62% 20.2% Six months Tsuang et al., 1979 31 Schizoaffective disorder 24 50 Inpatient USA 29.6 (ECT) and 30.5 (C) 71.4% Unknown 27 years (mean) Babigian et al., 1984 10 Mixed depression Varies Varies Mixed USA Varies Varies Varies 14 years Philibert et al, 1995 32 Unipolar depression 108 84 Inpatient USA 72.1 (ECT) and 70.9 (C) 64.8% 32.4% 11 years Munk-Olsen et al., 2007 33 Mixed 20,923 person-years Unknown Inpatient Denmark Unknown Unknown Unknown 25 years *Nordenskjold et al., 2013 34 MDD 28 28 Inpatient Sweden 52 (ECT) and 62 (C) 57% 36% 1 year Ahmadi et al,, 2016 16 MDD/ PTSD 92 3,393 Inpatient USA 52 (ECT) and 53 (C) 14.0% Unknown 8 years Liang et al., 2017 35 Mixed 1,571 827,328 Inpatient USA 42.1 (ECT) and 54.4 (C) 57.5% Unknown Up to 16 years Liang et al., 2018 36 MDD/bipolar depression 487 1,948 Inpatient Taiwan 38.5 (ECT) and 39.2 (C) 64.3% Unknown 4.4 years (median) Jorgensen et al., 2020 37 MDD 5,004 87,891 Mixed (38.0% inpatient) Denmark Ranged from 10 to 101 62.5% 5.1% Variable Osler et al., 2021 19 MDD/bipolar depression 6,943 167,552 Mixed Denmark Ranged from 80 62.0% 3.1% 6.7 years Rhee et al., 2021 17 MDD 10,460 31,160 Inpatient USA (Medicare) 74.7 on average 65.3% 1.0% 1 year Ronnqvist et al., 2021 18 MDD 5,525 5,525 Inpatient Sweden 55.9 (ECT) and 45.2 (C) 58.0% 23.8% 1 year Watts et al., 2021; 38 2022 47 Mixed 5,097 10,097 Inpatient USA (VA) 55.7 (ECT) and 55.9 (C) 12.3% Unknown 1 year Kaster et al., 2022 20 MDD/bipolar depression 4,982 5,304 Inpatient Canada 57.5 (ECT) and 57.1 (C) 65.9% 21.1% 1 year Yamazaki et al., 2022 39 Bipolar depression 215 860 Inpatient Japan 55.4 (ECT) and 56.3 (C) 61.0% 28.8% 1 year All-cause Mortality Overall, 13 studies 16–20,29−35,38,39 reported the effects of ECT on all-cause mortality (Fig. 2 ). When these 13 effect sizes were meta-synthesized, patients who received ECT had a lower risk of all-cause mortality (HR, 0.70 [95% CI, 0.61–0.81]; k = 13; p < 0.001). The cumulative forest plot by publication year is reported in Supplementary Fig. 1 . When stratified by specified follow-up times, this association was significant at 3 months (HR, 0.53 [95% CI, 0.39–0.72]; k = 4; p < 0.001), 6 months (HR, 0.64 [95% CI, 0.55–0.73]; k = 5; p < 0.001), and 12 months (HR, 0.72 [95% CI, 0.61–0.86]; k = 7; p < 0.001) ( Supplementary Figs. 3B, 3C, and 3D ). The association at 1 month of follow-up was of similar magnitude as the association at month 3, but was not statistically significant (HR, 0.49 [95% CI, 0.20–1.18]; k = 3; p = 0.11), likely due to fewer studies reporting at this time point. Suicide Mortality Overall, 12 studies 15 – 18 , 20 , 29 – 31 , 33 , 34 , 36 – 38 reported the effects of ECT on suicide deaths. When these 12 effect sizes were meta-synthesized, there was no association between ECT and the risk of suicide deaths (HR, 0.83 [95% CI, 0.51–1.34]; k = 12; p = 0.44) (Fig. 3 ). The cumulative forest plot by publication year is reported in Supplementary Fig. 2 . When stratified by specified follow-up times ( Supplementary Figs. 4A, 4C, and 4D ), an association was observed between ECT receipt and reduced risk of suicide at 3 months (HR = 0.53 [95% CI 0.39, 0.72]; k = 4; p < 0.001) ( Supplementary Fig. 4B ) but not at 1 month (k = 2), 6 months (k = 3), or 12 months (k = 8). Moderator analysis We explored potential moderating roles of the following variables using meta-regression (for continuous measures) or meta-ANOVA (for binary or categorical measures) models: study sample size; type of relative risk (i.e., HR, OR, or RR); age; female sex (%); follow-up duration; diagnosis; and country of study. Female sex had a statistically significant but very small moderating effect, with females experiencing a slightly smaller ECT effect on mortality. For all-cause mortality as an outcome of interest, we identified country of study as a potential moderator of outcomes ( p = 0.002) (Table 2 ). Each country has reported a lower risk of all-cause mortality, but the effect sizes vary by country. Japan had the largest effect size (HR = 0.17, 95% CI 0.04 to 0.72; k = 1) and Denmark had the smallest (HR = 0.87, 95% CI 0.83 to 0.92, k = 2). We have also reported the findings of moderator analysis for all-cause mortality by the follow-up period in Supplementary Table 3 . The number of patients enrolled in the component studies was considered a potential moderator of suicide deaths ( p < 0.001) (Table 3 ). We have also reported the findings of moderator analysis for suicide deaths by the follow-up period in Supplementary Table 4 . Table 2 Moderation analyses of all-cause mortality in ECT Moderator k Coefficient (95% CI) Hazard ratio (95% CI) P -value Number of total patients 13 0.00 (-0.00 to 0.00) - 0.915 * Outcome measure Hazard ratio 10 - 0.65 (0.54–0.79) 0.081 † Odds ratio 1 - 0.87 (0.73–1.03) Relative risk 2 - 0.72 (0.46–1.12) Age Overall 12 0.01 (-0.01 to 0.03) - 0.269 * 65 or older only 4 0.01 (-0.01 to 0.03) - 0.238 * Female sex 11 -0.01 (-0.01 to -0.00) - 0.036 * Follow-up duration 10 0.05 (-0.01 to 0.11) - 0.125 * Condition % major depressive disorder 9 0.00 (-0.02 to 0.02) - 0.985 * % psychotic depression 5 0.01 (-0.00 to 0.01) - 0.223 * % bipolar disorder 6 -0.00 (-0.02 to 0.01) - 0.506 * % psychosis or schizophrenic spectrum disorder 6 -0.01 (-0.02 to 0.00) - 0.155 * Region United States 6 - 0.52 (0.32–0.83) 0.002 † Canada 1 - 0.75 (0.58–0.97) Sweden 2 - 0.67 (0.55–0.82) Denmark 2 - 0.87 (0.83–0.92) Japan 1 - 0.17 (0.04–0.72) Taiwan 1 - 0.66 (0.46–0.94) Table 3 Moderation analyses of suicide in ECT Moderator k Coefficient (95% CI) Hazard ratio (95% CI) P -value Number of total patients 12 0.00 (0.00–0.00) - < 0.001 * Outcome measure Hazard ratio 9 - 0.77 (0.40–1.50) 0.225 † Odds ratio 1 - 1.38 (0.95–2.01) Relative risk 2 - 0.70 (0.21–2.25) Age Overall 10 0.01 (-0.05 to 0.06) - 0.858 * 65 or older only 3 0.01 (-0.01 to 0.03) - 0.340 * Female sex 9 -0.00 (-0.02 to -0.01) - 0.639 * Follow-up duration 10 0.10 (-0.10 to 0.30) - 0.312 * Condition % major depressive disorder 8 -0.02 (-0.04 to 0.01) - 0.233 * % psychotic depression 4 -0.01 (-0.03 to 0.01) - 0.170 * % bipolar disorder 6 0.01 (-0.00 to 0.03) - 0.149 * % psychosis or schizophrenic spectrum disorder 6 -0.00 (-0.21 to 0.21) - 0.997 * Region United States 6 - 0.58 (0.29–1.18) 0.251 † Canada 1 - 0.53 (0.31–0.91) Sweden 2 - 0.72 (0.52-1.00) Denmark 2 - 2.27 (0.63–8.26) Taiwan 1 - 0.80 (0.65–0.99) Methodological quality and publication bias Methodological quality of the included studies and our justification were provided in Supplementary Table 5 in the Supplement. Studies published after 2005 were considered ‘ good ,’ and studies published in the 1980’s or earlier were considered ‘ poor ’ to ‘ fair .’ Only one study 34 was a randomized controlled trial, where the risk of bias was considered ‘ low .’ In our main analysis, we did not find any potential publication bias for all-cause mortality as the primary outcome of interest ( Supplementary Fig. 5 ), using Egger’s test ( p = 0.10) and Begg and Mazumdar’s test ( p = 0.14). For suicide deaths as the outcome of interest ( Supplementary Fig. 6 ), we did not find any potential publication bias using Egger’s test ( p = 0.50) and Begg and Mazumdar’s test ( p = 0.89). DISCUSSION In this meta-analysis comprising over 41,000 patients that received ECT, it was determined that ECT was associated with a reduction in risk of all-cause mortality, a finding that was consistent at 3 months, 6 months, and 12 months of follow-up. Sex demonstrated a statistically significant but very small moderating effect on this relationship, with ECT being slightly less protective against all-cause mortality risk for females compared to males. Country also had a moderating effect. Each country has reported a lower risk of all-cause mortality associated with ECT, but the effect sizes vary by country. Japan had the largest effect size whereas Denmark had the smallest. ECT was associated with a reduction in suicide risk at 3 months of follow-up but not at 1, 6, or 12 months of follow-up. The findings of this meta-analysis suggest a treatment effect whereby ECT reduces the risk of all-cause mortality. Possible mechanisms whereby ECT may have a causal protective effect on mortality include both psychological/functional and biological mechanisms. With respect to a psychological/functional mechanism, one potential way in which ECT might lead to reduction in all-cause mortality risk is that ECT may help improve functioning, allowing patients to better engage in treatment for whatever medical conditions they face or maintain a healthier lifestyle. This is supported by a prior report wherein ECT recipients were less likely to die from a variety of causes, including smoking-related causes, cancer, circulatory diseases, and diabetes. 17 With respect to potential biological mechanisms, ECT has been shown to reduce markers of neurodegeneration, and may also help improve innate immune functioning in individuals with depression. 40 Successful treatment of mental illness may also normalize pathological vascular states that have been linked to mood disorders. 41 Given that most studies included in this meta-analysis were observational in nature, the possibility that confounding explains this association must be considered. 42 It is possible that patients with severe medical illness are not selected for ECT because of the risk of the procedure. We judge that confounding cannot account for the whole of the association between ECT and reduced mortality risk. One such reason is because many of the more recent, methodologically sophisticated longitudinal studies show a substantial difference between ECT and non-ECT groups in terms of mortality risk after carefully balancing known medical comorbidities. For instance, Kaster et al., conducted an assessment in which each of a range of 25 serious medical conditions were matched between the groups with a standardized mean difference of 0.02 or less. 20 Rhee et al., conducted a sub-analysis wherein patients who received a subtherapeutic course of ECT (defined to be 4 treatments or fewer) were compared to those receiving a therapeutic course and those who did not receive ECT. 17 The trajectory of mortality risk of those receiving a subtherapeutic course of ECT matched those who did not receive ECT for the first 6 months following hospital discharge (both of these groups were at greater risk of mortality compared to the therapeutic ECT group). 17 Hence, while confounding may explain some of the observed association between ECT utilization and lower risk of all-cause mortality, several lines of evidence suggest that confounding does not explain all of the association. Previous studies on the possible effects of ECT on suicide have been inconsistent. 43 Notably, treatment guidelines from the American Psychiatric Association as well as the Canadian Network for Mood and Anxiety Treatments recommend the use of ECT for those with acute suicidal ideation. 44 The current meta-analysis did not find a consistent relationship between ECT and suicide risk. Notably, for those studies (k = 4) that specifically reported outcomes 3 months after index date, a significant association was found between ECT receipt and reduced risk of suicide death. No association was found at months 1 (k = 2), 6 (k = 3), or 12 (k = 8). Possibile explanations include discrepancies in power (for 1- and 6-month outcomes) and/or that any protective effect of ECT against suicide wanes beyond 3 months, especially if patients do not continue to receive continuation/maintenance therapy. It has long been shown that relapse rates are quite high (84%) among ECT responders by 6 months if no continuation/maintenance therapy is initiated. 45 Our analysis suggested that the association between ECT and all-cause mortality is slightly weaker for females than for males (standardized beta coefficient, -0.01). The significance of this finding is uncertain and, to our knowledge, has not been reported previously. This analysis also showed that country also had a moderating effect. Each country has reported a lower risk of all-cause mortality associated with ECT, but the effect sizes vary by country. The significance of this is unknown. Of note, all countries except the United States only had two or fewer studies. Several limitations of the current study require comment. As noted, confounding cannot be entirely ruled out, as most studies included in this meta-analysis were non-randomized. Additionally, as is usually the case in meta-analyses, studies varied in the way outcomes were reported. This resulted in small numbers of studies for time-specific outcomes (k = 2, for ECT and suicide association at 1 month). Furthermore, most studies did not report on what types of treatment were received at the conclusion of the index course of ECT. It has long been noted that the type of continuation/maintenance therapy can have a large bearing on clinical outcomes. 45 , 46 Conclusions ECT is strongly associated with a reduced risk of all-cause mortality. This finding is seen internationally, across age groups and sexes. While confounding cannot be entirely ruled out due to most studies being non-randomized, recent large and high-quality studies that controlled for many measures of medical comorbidity affirmed this finding. ECT is not consistently associated with a reduced risk of suicide. Declarations Acknowledgement and disclosures Study approval statement :An ethics statement is not applicable because this study is based exclusively on published literature. Consent to participate statement : Written informed consent was not required as this study is based exclusively on published literature. Data availability statement : Data are publicly available. All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author. Author contributions : Study concept and design: TGR; Data acquisition and statistical analyses: TGR & SRS; Interpretation of data: TGR, SRS, MN, RSM, TSK, & STW; Drafting of manuscript: TGR, SRS, MN, & STW; Critical revision of manuscript for important intellectual content: TGR, SRS, MN, RSM, TSK, & STW; Supervision: TGR & STW. TGR and SRS are co-first authors. TGR had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Role of the funder/sponsor : This study was not funded. Conflict of interest disclosures : Each author completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and had none directly related to this manuscript. Rhee was supported in part by the National Institute on Aging (NIA) (#R21AG070666; R21AG078972), National Institute of Mental Health (#R21MH117438), National Institute on Drug Abuse (#R21DA057540) and Institute for Collaboration on Health, Intervention, and Policy (InCHIP) of the University of Connecticut. Dr. Rhee serves as a review committee member for Patient-Centered Outcomes Research Institute (PCORI) and Substance Abuse and Mental Health Services Administration (SAMHSA) and has received honoraria payments from PCORI and SAMHSA. Dr. Rhee has also served as a stakeholder/consultant for PCORI and received consulting fees from PCORI. Dr. Rhee serves as an advisory committee member for International Alliance of Mental Health Research Funders (IAMHRF). Shim reported none. Nasir reported none. McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC); speaker/consultation fees from Lundbeck, Janssen, Alkermes, Mitsubishi, Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk,Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie, Atai Life Sciences. Kaster is supported by the Canadian Institute for Health Research, the AFP Innovation Fund, and the Patient-Centered Outcomes Research Institute. Wilkinson reported receiving funding from Sage Therapeutics and Oui Therapeutics for the conduct of clinical trials (administered through Yale University) and personal fees from LivaNova and Mind Medicine outside the submitted work. Funding : This study was not funded. References World Health Organization. Depression. Accessed January 27, 2025. https://www.who.int/news-room/fact-sheets/detail/depression Chang CK, Hayes RD, Perera G, et al. Life expectancy at birth for people with serious mental illness and other major disorders from a secondary mental health care case register in London. PloS one. 2011;6(5):e19590. doi: 10.1371/journal.pone.0019590 Lemogne C, Nabi H, Melchior M, et al. Mortality associated with depression as compared with other severe mental disorders: a 20-year follow-up study of the GAZEL cohort. Journal of psychiatric research. Jul 2013;47(7):851–7. doi: 10.1016/j.jpsychires.2013.03.015 Lemogne C, Niedhammer I, Khlat M, et al. 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Jan 2015;172(1):52–8. doi: 10.1176/appi.ajp.2014.13060787 Avery D, Winokur G. Mortality in depressed patients treated with electroconvulsive therapy and antidepressants. Archives of General Psychiatry. 1976;33(9):1029–1037. Babigian HM, Guttmacher LB. Epidemiologic considerations in electroconvulsive therapy. Comparative Study. Archives of General Psychiatry. Mar 1984;41(3):246–53. Kellner CH, Fink M, Knapp R, et al. Relief of expressed suicidal intent by ECT: a consortium for research in ECT study. Am J Psychiatry. May 2005;162(5):977–82. doi: 10.1176/appi.ajp.162.5.977 American Psychiatric Association. Task Force on Electroconvulsive Therapy. The practice of electroconvulsive therapy: recommendations for treatment, training, and privileging . Third edition. ed. American Psychiatric Association; 2024:pages cm. Milev RV, Giacobbe P, Kennedy SH, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 4. Neurostimulation Treatments. Can J Psychiatry. Sep 2016;61(9):561–75. doi: 10.1177/0706743716660033 Wilkinson ST, Trujillo Diaz D, Rupp ZW, et al. Pharmacological and somatic treatment effects on suicide in adults: A systematic review and meta-analysis. Depression and anxiety. Nov 11 2021;doi: 10.1002/da.23222 Avery D, Winokur G. Suicide, attempted suicide, and relapse rates in depression. Archives of General Psychiatry. Jun 1978;35(6):749–753. doi: https://dx.doi.org/10.1001/archpsyc.1978.01770300091010 Ahmadi N, Moss L, Simon E, Nemeroff CB, Atre-Vaidya N. Efficacy and long-term clinical outcome of comorbid posttraumatic stress disorder and major depressive disorder after electroconvulsive therapy. Empirical Study; Followup Study; Longitudinal Study; Retrospective Study; Quantitative Study. Depression and Anxiety. Jul 2016;33(7):640–647. doi: https://dx.doi.org/10.1002/da.22451 Rhee TG, Sint K, Olfson M, Gerhard T, Busch SH, Wilkinson ST. Association of ECT with risks of all-cause mortality and suicide in older Medicare patients. Empirical Study; Quantitative Study. The American Journal of Psychiatry. Dec 2021;178(12):1089–1097. doi: https://dx.doi.org/10.1176/appi.ajp.2021.21040351 Ronnqvist I, Nilsson FK, Nordenskjold A. Electroconvulsive Therapy and the Risk of Suicide in Hospitalized Patients with Major Depressive Disorder. JAMA Network Open. 21 Jul 2021;4(7) (no pagination)e2116589. doi: https://dx.doi.org/10.1001/jamanetworkopen.2021.16589 Osler M, Rozing MP, Jorgensen MB, Jorgensen A. Mortality and acute somatic events following electroconvulsive therapy in patients with pre-existing somatic comorbidity - a register-based nationwide danish cohort study. The World Journal of Biological Psychiatry . Nov 2021:No Pagination Specified. doi: https://dx.doi.org/10.1080/15622975.2021.1995808 Kaster TS, Blumberger DM, Gomes T, Sutradhar R, Wijeysundera DN, Vigod SN. Risk of suicide death following electroconvulsive therapy treatment for depression: a propensity score-weighted, retrospective cohort study in Canada. Research Support, Non-U.S. Gov't. Lancet Psychiatry. 06 2022;9(6):435–446. doi: https://dx.doi.org/10.1016/S2215-0366(22)00077-3 Brooke BS, Schwartz TA, Pawlik TM. MOOSE Reporting Guidelines for Meta-analyses of Observational Studies. JAMA Surg. Aug 1 2021;156(8):787–788. doi: 10.1001/jamasurg.2021.0522 Higgins JPT, Cochrane Collaboration. Cochrane handbook for systematic reviews of interventions . Second edition. ed. Cochrane book series. Wiley-Blackwell; 2019:xxviii, 694 pages. Lo CK, Mertz D, Loeb M. Newcastle-Ottawa Scale: comparing reviewers' to authors' assessments. BMC Med Res Methodol. Apr 1 2014;14:45. doi: 10.1186/1471-2288-14-45 Cooper H, Hedges LV, Valentine JC. The handbook of research synthesis and meta-analysis . Russell Sage Foundation; 2019. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Bmj. 1997;315(7109):629–634. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. Dec 1994;50(4):1088–101. Veroniki AA, Jackson D, Viechtbauer W, et al. Methods to estimate the between-study variance and its uncertainty in meta-analysis. Res Synth Methods. Mar 2016;7(1):55–79. doi: 10.1002/jrsm.1164 Shim SR, Kim SJ. Intervention meta-analysis: application and practice using R software. Epidemiol Health. 2019;41:e2019008. doi: 10.4178/epih.e2019008 Huston PE, Locher LM. Manic-depressive psychosis; course when treated and untreated with electric shock. Archives of Neurology & Psychiatry. 1948;60:37–48. doi: https://dx.doi.org/10.1001/archneurpsyc.1948.02310010043003 Huston PE, Locher LM. Involutional psychosis; course when untreated and when treated with electric shock. Archives of Neurology & Psychiatry. 1948;59:385–394. doi: https://dx.doi.org/10.1001/archneurpsyc.1948.02300380114010 Tsuang MT, Dempsey G, Fleming JA. Can ECT prevent premature death and suicide in schizoaffective patients? Empirical Study; Followup Study. Journal of Affective Disorders. Sep 1979;1(3):167–171. doi: https://dx.doi.org/10.1016/0165-0327%2879%2990001-6 Philibert RA, Richards L, Lynch CF, Winokur G. Effect of ECT on mortality and clinical outcome in geriatric unipolar depression. Empirical Study. The Journal of Clinical Psychiatry. Sep 1995;56(9):390–394. Munk-Olsen T, Laursen TM, Videbech P, Mortensen PB, Rosenberg R. All-cause mortality among recipients of electroconvulsive therapy: Register-based cohort study. Empirical Study; Followup Study; Quantitative Study. The British Journal of Psychiatry. May 2007;190:435–439. doi: https://dx.doi.org/10.1192/bjp.bp.106.026740 Nordenskjöld A, von Knorring L, Ljung T, Carlborg A, Brus O, Engström I. Continuation electroconvulsive therapy with pharmacotherapy versus pharmacotherapy alone for prevention of relapse of depression: a randomized controlled trial. Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't. Journal of ECT. 2013;29(2):86‐92. doi: 10.1097/YCT.0b013e318276591f Liang C, Chung C, Tsai C, Chien W. In-hospital mortality among electroconvulsive therapy recipients: A 17-year nationwide population-based retrospective study. Empirical Study; Longitudinal Study; Retrospective Study; Quantitative Study. European Psychiatry. May 2017;42:29–35. doi: https://dx.doi.org/10.1016/j.eurpsy.2016.12.005 Liang CS, Chung CH, Ho PS, Tsai CK, Chien WC. Superior anti-suicidal effects of electroconvulsive therapy in unipolar disorder and bipolar depression. Bipolar Disorders. 09 2018;20(6):539–546. doi: https://dx.doi.org/10.1111/bdi.12589 Jorgensen MB, Rozing MP, Kellner CH, Osler M. Electroconvulsive therapy, depression severity and mortality: Data from the Danish National Patient Registry. Research Support, Non-U.S. Gov't. Journal of Psychopharmacology. 03 2020;34(3):273–279. doi: https://dx.doi.org/10.1177/0269881119895518 Watts BV, Peltzman T, Shiner B. Mortality after electroconvulsive therapy. Research Support, U.S. Gov't, Non-P.H.S. British Journal of Psychiatry. 11 2021;219(5):588–593. doi: https://dx.doi.org/10.1192/bjp.2021.63 Yamazaki R, Ohbe H, Matsuda Y, et al. Early electroconvulsive therapy in patients with bipolar depression: A propensity score-matched analysis using a nationwide inpatient database. Journal of Affective Disorders. 01 Sep 2022;312:245–251. doi: https://dx.doi.org/10.1016/j.jad.2022.06.060 Kranaster L, Hoyer C, Aksay SS, et al. Biomarkers for Antidepressant Efficacy of Electroconvulsive Therapy: An Exploratory Cerebrospinal Fluid Study. Neuropsychobiology. 2019;77(1):13–22. doi: 10.1159/000491401 Goldstein BI, Baune BT, Bond DJ, et al. Call to action regarding the vascular-bipolar link: A report from the Vascular Task Force of the International Society for Bipolar Disorders. Bipolar Disord. Aug 2020;22(5):440–460. doi: 10.1111/bdi.12921 Bharadwaj R, Grover S. Mortality and electroconvulsive therapy. Br J Psychiatry. Oct 2007;191:362–3; author reply 363. doi: 10.1192/bjp.191.4.362a Prudic J, Sackeim HA. Electroconvulsive therapy and suicide risk. J Clin Psychiatry. 1999;60 Suppl 2:104 – 10; discussion 111-6. American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder. Accessed jUNE 7, 2020. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf Sackeim HA, Haskett RF, Mulsant BH, et al. Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial. JAMA. Mar 14 2001;285(10):1299–307. doi: 10.1001/jama.285.10.1299 Jorgensen A, Gronemann FH, Rozing MP, Jorgensen MB, Osler M. Clinical Outcomes of Continuation and Maintenance Electroconvulsive Therapy. JAMA Psychiatry. Dec 1 2024;81(12):1207–1214. doi: 10.1001/jamapsychiatry.2024.2360 Watts BV, Peltzman T, Shiner B. Electroconvulsive Therapy and Death by Suicide. Research Support, Non-U.S. Gov't. Journal of Clinical Psychiatry . 04 13 2022;83(3):13. doi: https://dx.doi.org/10.4088/JCP.21m13886 Additional Declarations Yes Please see our authors statement at the end of the manuscript. The authors do not have COIs directly related to the work. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6180102","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":430697587,"identity":"ff144ecf-cf65-4969-9bbc-cf4d4f523db7","order_by":0,"name":"Taeho Greg Rhee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAUlEQVRIiWNgGAWjYHACNmTOATkw+QCPeh50LcZgMoEULYkNIAqfFnv+tc8efKhgyOfnP3zwc0XNnfT5YYcfAm2xk9NtwGGLxHNzwxlnGCxnzkhLljxz7FnuxttpBkAtycZmB3BpOcYmzdvGYGBwg8dAsrHhcO7G2QkgLQcSt+HT8vcfg4H9+fOffwK1pBvOTv+AXwt/G5s0YwPQFoYcNpAtCfLSOQRsucHGJtlzTMJA4kaamWXDscOGG6RzCg4kGOD2C3v/MTaJHzU2Bvz9hx/fbKg5LC8/O33zhw8VdnK4tDBIJIBJhIABWKUBDuUgwI9ulnwDHtWjYBSMglEwIgEAro5goW6weuEAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0003-4961-3361","institution":"Yale School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Taeho","middleName":"Greg","lastName":"Rhee","suffix":""},{"id":430697588,"identity":"d1c3ed83-6352-415e-add6-0d9999f5f3f7","order_by":1,"name":"sungryul shim","email":"","orcid":"https://orcid.org/0000-0003-4143-7383","institution":"Konyang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"sungryul","middleName":"","lastName":"shim","suffix":""},{"id":430697589,"identity":"f83d61bb-e902-4b57-bccf-5be93a788975","order_by":2,"name":"Madeeha Nasir","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Madeeha","middleName":"","lastName":"Nasir","suffix":""},{"id":430697590,"identity":"6e7ea381-15ef-456b-9783-d5c9c23f6b6a","order_by":3,"name":"Roger McIntyre","email":"","orcid":"","institution":"Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada","correspondingAuthor":false,"prefix":"","firstName":"Roger","middleName":"","lastName":"McIntyre","suffix":""},{"id":430697591,"identity":"f27461a8-87a2-4840-85ea-07700bfc6d7c","order_by":4,"name":"Tyler Kaster","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Tyler","middleName":"","lastName":"Kaster","suffix":""},{"id":430697592,"identity":"cc994a74-6ab5-452a-b6d3-f62db6626f08","order_by":5,"name":"Samuel Wilkinson","email":"","orcid":"","institution":"Yale University","correspondingAuthor":false,"prefix":"","firstName":"Samuel","middleName":"","lastName":"Wilkinson","suffix":""}],"badges":[],"createdAt":"2025-03-07 17:31:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6180102/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6180102/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79562596,"identity":"cb2b284e-9750-4d60-b953-c160e106b708","added_by":"auto","created_at":"2025-03-31 08:57:58","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":567062,"visible":true,"origin":"","legend":"\u003cp\u003eStudy selection flowchart\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNote\u003c/strong\u003e: *PICOTS indicates population, intervention, comparator, outcome, timing, and setting.\u003c/p\u003e","description":"","filename":"Figure1Studyselectionflowchart.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6180102/v1/d86fca832a5149d9e75f36a6.jpg"},{"id":79562597,"identity":"19a17527-283d-408f-9562-c171de0ee41d","added_by":"auto","created_at":"2025-03-31 08:57:59","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":418276,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of all-cause mortality in ECT\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNote\u003c/strong\u003e: A hazard ratio of \u0026lt;1.0 indicates a reduction of suicide deaths in the ECT group (i.e., favors ECT).\u003c/p\u003e","description":"","filename":"Figure2Allcausemortalitybyyear.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6180102/v1/10e79833ab8e487bb3494f51.jpg"},{"id":79563382,"identity":"b6cffe68-010d-47d4-af5d-79c13663b8c2","added_by":"auto","created_at":"2025-03-31 09:05:59","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":428772,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of suicide mortality in ECT\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNote\u003c/strong\u003e: A hazard ratio of \u0026lt;1.0 indicates a reduction of suicide deaths in the ECT group (i.e., favors ECT).\u003c/p\u003e","description":"","filename":"Figure3Suicidemortalitybyyear.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6180102/v1/c7a8630e91cc1d7a2b61bb93.jpg"},{"id":85878114,"identity":"52467588-7781-4a5f-a5a5-c0eb820d4b60","added_by":"auto","created_at":"2025-07-02 15:35:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2598428,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6180102/v1/a52cee1c-582b-43ba-9baf-6641c9faf9f7.pdf"},{"id":79563384,"identity":"f4c4ab51-52ca-4895-9b87-5d78a34390d7","added_by":"auto","created_at":"2025-03-31 09:05:59","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":897269,"visible":true,"origin":"","legend":"Supplemental Materials","description":"","filename":"ECTandmortalityMASupplement372025.docx","url":"https://assets-eu.researchsquare.com/files/rs-6180102/v1/04c615f3b26b04cbf4cc9024.docx"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e\nPlease see our authors statement at the end of the manuscript. The authors do not have COIs directly related to the work.","formattedTitle":"Longitudinal Associations of Electroconvulsive Therapy with All-cause Mortality and Suicide Deaths in Depression and Other Psychiatric Disorders: A Systematic Review and Meta-Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMood disorders are a leading cause of disability and mortality.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Mood disorders are associated with a dramatically reduced life expectancy, translating to approximately 10 years of lost life expectancy among males and 7\u0026ndash;11 years among females.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Those who suffer from mood disorders are at an increased risk of suicide when compared to the general population. However, increased rates of mortality among this group are not solely attributable to suicide; risks for deaths due to cardiovascular disease, cancer, and other comorbid medical conditions are also elevated among individuals with mood disorders.\u003csup\u003e\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Individuals with schizophrenia spectrum and other psychotic disorders are also at considerably elevated risk of premature mortality (including suicide) compared to the general population.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eElectroconvulsive therapy (ECT) is among the most effective treatments for mood disorders,\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e and also has efficacy for treatment-resistant psychotic disorders.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Prior research suggests that ECT may reduce the risk of suicide as well as all-cause mortality. However, several methodological limitations cast uncertainty over this conclusion. For instance, one early study followed 135 patients who received ECT from a single state psychiatric facility. While this report showed a reduced risk of all-cause mortality, baseline differences between the group receiving ECT and the group that did not receive ECT were not accounted for.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Another study from the state of New York reported a higher mortality risk among ECT patients; again, there was no attempt to account for baseline clinical differences between cohorts.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eClinical practice standards suggest ECT should be considered for patients with mood disorders at risk of suicide.\u003csup\u003e\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e However, the evidence of the effects of ECT on suicide deaths have been inconsistent.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e While some studies suggest a protective effect of ECT against suicide,\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e other studies report that any protective effect is quite transient.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Given the nature of ECT, blinded studies are no longer possible. In addition, as ECT is most commonly given to the most severely ill patients, observational studies that sufficiently account for potential confounding factors are crucial to further elucidating this relationship.\u003c/p\u003e \u003cp\u003eIn the last few years, a number of high-quality longitudinal studies examining the relationship between ECT, all-cause mortality and suicide using large databases have been published.\u003csup\u003e\u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e In the present study, we conduct a systematic review and meta-analysis that include these recent large and high-quality studies to better clarify the effects of ECT on all-cause mortality and suicide deaths among patients with psychiatric conditions.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch3\u003eSearch strategy\u003c/h3\u003e\n\u003cp\u003eThe protocol pertaining to this study was registered on PROSPERO (CRD42025641749). A systematic search was conducted from inception to January 21, 2025. The following databases were systematically searched: PubMed/MEDLINE, PsycINFO, the Cochrane Library, and Embase using Medical Subject Headings (MeSH) terms and text keywords. We also manually searched all relevant studies in GoogleScholar (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://scholar.google.com/\u003c/span\u003e\u003cspan address=\"https://scholar.google.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). No language restrictions were imposed. Search strategies are provided in \u003cb\u003eSupplementary Table\u0026nbsp;1\u003c/b\u003e in the Supplement. Two authors (TGR and SRS) independently identified relevant studies among the results of the systematic search. References of included studies were also screened for relevant studies. This study followed the preferred reporting items for meta-analysis of observational studies in epidemiology (MOOSE) reporting guidelines (\u003cb\u003eSupplementary Table\u0026nbsp;2\u003c/b\u003e).\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e Our study used publicly available data and did not include human participant research. As per 45 CFR \u0026sect;\u0026nbsp;46.102(f), this study was not submitted for institutional review board approval and did not require informed consent procedures.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEligibility criteria and study selection\u003c/h2\u003e \u003cp\u003eInclusion criteria were established prior to article reviews and were as follows: (1) patients with a diagnosis of mental disorder using standardized diagnostic criteria (e.g., \u003cem\u003eDiagnostic and Statistical Manual of Mental Disorders, fifth Edition\u003c/em\u003e [DSM-5] or \u003cem\u003eInternational Statistical Classification of Diseases and Related Health Problems, Tenth Revision\u003c/em\u003e [ICD-10]); (2) intervention/comparator groups consisted of ECT compared with placebo, usual care, or another intervention; (3) outcome measures of validated all-cause mortality or suicide deaths; and (4) randomized controlled trial or longitudinal cohort study designs where the aforementioned interventions preceded the observations of outcome measures. Exclusion criteria were as follow: (1) non-human studies; (2) no use of standardized measures for mental disorder or primary outcomes of interest; or (3) case-control or anecdotal (e.g., case series, case reports, and editorials) study designs. Within-group comparisons (i.e., when participants were receiving the ECT compared to when they were not) were excluded, as were studies using historical comparisons.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy identification and data extraction\u003c/h3\u003e\n\u003cp\u003eTitles and abstracts were independently screened by two reviewers (TGR and SRS), and articles identified as potentially relevant by at least one reviewer were retrieved and duplicates were removed. Full-text articles were independently screened by the same reviewers, and discrepancies were resolved through discussion. Data from included articles were independently extracted by the two reviewers using a pilot-tested data extraction form and then corroborated, with discrepancies resolved through discussion. Information to be extracted was established a priori and included: study characteristics (e.g., PICOTS framework), participant characteristics (e.g., clinical and diagnostic information as well as other co-morbidities), data source, selection of cases and controls, sample size and follow-up period, modes of ascertainment, methods of data analysis (e.g., relative measures using adjusted odds ratio [OR], hazard ratio [HR], or relative risk [RR]), and quantitative data pertaining to any primary and secondary outcomes along with covariates. For observational studies where cohort groups often differed with respect to person-time of exposure, we favored (where available) the use of person-years in the denominator. To ensure the absence of overlapping data and to maintain the integrity of the meta-analysis, data and references for each included study were carefully cross-checked.\u003c/p\u003e\n\u003ch3\u003eAssessment methodological quality\u003c/h3\u003e\n\u003cp\u003eThe risk of bias and methodological quality were evaluated using the Newcastle-Ottawa Scale (NOS) for the assessment of the quality of non-randomized studies in meta-analyses.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e We assessed eight items across three domains: selection (adequate definition of case; representativeness of case; definition of control; selection of control); comparability of cases and controls based on the design or analysis; and exposure/outcome (ascertainment of exposure or outcome; same method of ascertainment for cases and controls; and non-response rate). The overall quality was classified as being indicative of a \u0026lsquo;\u003cem\u003egood quality\u003c/em\u003e,\u0026rsquo; \u0026lsquo;\u003cem\u003efair quality\u003c/em\u003e,\u0026rsquo; or \u0026lsquo;\u003cem\u003epoor quality\u003c/em\u003e.\u0026rsquo;\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003ch3\u003ePublication bias\u003c/h3\u003e\n\u003cp\u003eWe used funnel plots to visually explore for evidence of association between the effect sizes and statistical precision.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e We supplemented visual assessments with statistical testing of funnel plot asymmetry using Egger\u0026rsquo;s test (i.e., a weighted linear regression of effect size versus precision)\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e and Begg and Mazumdar\u0026rsquo;s test (i.e., rank correlation test).\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e Evidence of associations between effect sizes and precision across studies may indicate design heterogeneity, chance or selection biases that operate cross the evidence base (e.g., publication and outcome reporting bias).\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe primary outcomes of interest for each comparison were (1) death by any cause (i.e., all-cause mortality) and (2) suicide deaths, assessed as described in each study (either through prospective observation or database analysis [e.g., the Nation Death Index or similar registries]). Where possible, the time over which the outcomes were assessed was standardized across studies (e.g., 3-, 6-, and 12-month follow-up periods). Because different studies reported three types of relative measures (i.e., OR, HR, and RR), we converted adjusted ORs and RRs to HRs. The weight of each study was determined using an inverse-variance method.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWe used both \u003cem\u003eI\u003c/em\u003e-squared statistic and Cochran\u0026rsquo;s \u003cem\u003eQ\u003c/em\u003e-statistic to quantify the proportions of heterogeneity due to within- and between-study variations.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e To adequately estimate the overall effect sizes, relative measures (e.g., ORs, HRs, or RRs) with their corresponding 95% confidence intervals (CIs) were calculated using fixed- or random-effects models depending on the model assumptions.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e More specifically, a random-effects model was used when \u003cem\u003eI\u003c/em\u003e-squared statistic was \u0026gt;\u0026thinsp;50% and a fixed-effects model was used when \u003cem\u003eI\u003c/em\u003e-squared statistic was \u0026lt;\u0026thinsp;50%. We reported both random- and fixed-effects models when \u003cem\u003eI\u003c/em\u003e-squares statistics was 50%.\u003c/p\u003e \u003cp\u003eThe \u003cem\u003eQ\u003c/em\u003e-statistic was used to assess between-study heterogeneity. This statistic provides a quantitative test indicating whether different effect sizes between studies are attributable to subject-level sampling alone or other sources of variability. We estimated the degree of heterogeneity using the \u003cem\u003eI\u003c/em\u003e-squared statistic, which estimates the proportion of total variance attributable to variance between different studies.\u003c/p\u003e \u003cp\u003e We also conducted moderator analyses using meta-regression analyses by study sample size; relative risk measure (e.g., OR, HR, and RR); age; female sex (%); diagnosis (including psychotic depression and bipolar depression); and country. When identifying potential moderators, we used the variance of the true effects using a restricted maximum likelihood (REML) estimator.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e We used a statistical software, R 4.2.1. [R Foundation for Statistical Computing] for all analyses using the \u0026ldquo;\u003cem\u003emeta\u003c/em\u003e\u0026rdquo; package.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e Finally, as mentioned earlier, we assessed publication bias (or small-study effects) using funnel plots;\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e Egger\u0026rsquo;s test and Begg and Mazumdar\u0026rsquo;s test were also performed when assessing the publication bias.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e Unless otherwise noted, a two-sided \u003cem\u003ep\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered for statistically significance.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eRole of the funding source\u003c/h2\u003e \u003cp\u003eThe funders were not involved in the study design, data collection, analysis, interpretation of data, writing of the report, or the decision to submit the manuscript for publication.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eCharacteristics of included studies\u003c/h2\u003e \u003cp\u003eThe literature search yielded 7,530 articles, of which 63 were eligible after screening titles and abstracts and removing duplicates. Of these eligible studies, 54 were further excluded after full-text screening. Two independent investigators (TGR and SRS) discovered 8 additional studies by manually searching reference lists and GoogleScholar (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Overall, 17 studies\u003csup\u003e9,10,15\u0026ndash;20,29\u0026minus;39\u003c/sup\u003e consisting of 1,182,501 subjects (n\u0026thinsp;=\u0026thinsp;40,867 for patients receiving ECT and n\u0026thinsp;=\u0026thinsp;1,141,634 for patients receiving other comparable interventions) were included in the review (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). From these studies, 13 effect sizes for all-cause mortality and 12 effect sizes for suicide deaths were identified for meta-analyses. Fourteen of 17 studies (82.4%) were conducted in inpatient settings, and 9 of 17 (52.9%) were conducted in the United States. Almost all studies had patients with unipolar or bipolar depression, except one study\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e that had patients with schizoaffective disorder. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e provides details of study characteristics, including mean age, proportion of female sex and follow-up time, for all included studies.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSelected characteristics of included studies for both qualitative and quantitative analyses\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAuthor and publication year\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSample size (ECT)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSample size (control)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInpatient v. outpatient\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCountry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMean age\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eProportion female\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eProportion psychotic depression\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFollow Up Time\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHuston et al., 1948\u003csup\u003e29,30\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDD/bipolar depression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eVaries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e56.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e29.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e35 months (median)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAvery et al., 1978\u003csup\u003e9\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDepression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e257\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e334\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e62%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e20.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSix months\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTsuang et al., 1979\u003csup\u003e31\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSchizoaffective disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e29.6 (ECT) and 30.5 (C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e71.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e27 years (mean)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBabigian et al., 1984\u003csup\u003e10\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMixed depression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVaries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eVaries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eVaries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eVaries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eVaries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e14 years\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhilibert et al, 1995\u003csup\u003e32\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnipolar depression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e72.1 (ECT) and 70.9 (C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e64.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e32.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e11 years\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMunk-Olsen et al., 2007\u003csup\u003e33\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20,923 person-years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDenmark\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e25 years\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e*Nordenskjold et al., 2013\u003csup\u003e34\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSweden\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e52 (ECT) and 62 (C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e57%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e36%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 year\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAhmadi et al,, 2016\u003csup\u003e16\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDD/ PTSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3,393\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e52 (ECT) and 53 (C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e14.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e8 years\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiang et al., 2017\u003csup\u003e35\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,571\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e827,328\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e42.1 (ECT) and 54.4 (C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e57.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eUp to 16 years\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiang et al., 2018\u003csup\u003e36\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDD/bipolar depression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e487\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,948\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTaiwan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e38.5 (ECT) and 39.2 (C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e64.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e4.4 years (median)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJorgensen et al., 2020\u003csup\u003e37\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5,004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e87,891\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMixed (38.0% inpatient)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDenmark\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRanged from 10 to 101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e62.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOsler et al., 2021\u003csup\u003e19\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDD/bipolar depression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6,943\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e167,552\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDenmark\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRanged from \u0026lt;\u0026thinsp;40 to \u0026gt;\u0026thinsp;80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e62.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e6.7 years\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRhee et al., 2021\u003csup\u003e17\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10,460\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31,160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUSA (Medicare)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e74.7 on average\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e65.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 year\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRonnqvist et al., 2021\u003csup\u003e18\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5,525\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5,525\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSweden\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e55.9 (ECT) and 45.2 (C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e58.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e23.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 year\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWatts et al., 2021;\u003csup\u003e38\u003c/sup\u003e2022\u003csup\u003e47\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMixed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5,097\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10,097\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eUSA (VA)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e55.7 (ECT) and 55.9 (C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 year\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKaster et al., 2022\u003csup\u003e20\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDD/bipolar depression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4,982\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5,304\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCanada\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e57.5 (ECT) and 57.1 (C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e65.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e21.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 year\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYamazaki et al., 2022\u003csup\u003e39\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBipolar depression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e215\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e860\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInpatient\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e55.4 (ECT) and 56.3 (C)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e61.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e28.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1 year\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eAll-cause Mortality\u003c/h2\u003e \u003cp\u003eOverall, 13 studies\u003csup\u003e16\u0026ndash;20,29\u0026minus;35,38,39\u003c/sup\u003e reported the effects of ECT on all-cause mortality (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). When these 13 effect sizes were meta-synthesized, patients who received ECT had a lower risk of all-cause mortality (HR, 0.70 [95% CI, 0.61\u0026ndash;0.81]; k\u0026thinsp;=\u0026thinsp;13; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The cumulative forest plot by publication year is reported in \u003cb\u003eSupplementary Fig.\u0026nbsp;1\u003c/b\u003e. When stratified by specified follow-up times, this association was significant at 3 months (HR, 0.53 [95% CI, 0.39\u0026ndash;0.72]; k\u0026thinsp;=\u0026thinsp;4; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), 6 months (HR, 0.64 [95% CI, 0.55\u0026ndash;0.73]; k\u0026thinsp;=\u0026thinsp;5; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and 12 months (HR, 0.72 [95% CI, 0.61\u0026ndash;0.86]; k\u0026thinsp;=\u0026thinsp;7; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (\u003cb\u003eSupplementary Figs.\u0026nbsp;3B, 3C, and 3D\u003c/b\u003e). The association at 1 month of follow-up was of similar magnitude as the association at month 3, but was not statistically significant (HR, 0.49 [95% CI, 0.20\u0026ndash;1.18]; k\u0026thinsp;=\u0026thinsp;3; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.11), likely due to fewer studies reporting at this time point.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSuicide Mortality\u003c/h2\u003e \u003cp\u003eOverall, 12 studies\u003csup\u003e\u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e,\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e,\u003cspan additionalcitationids=\"CR37\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e reported the effects of ECT on suicide deaths. When these 12 effect sizes were meta-synthesized, there was no association between ECT and the risk of suicide deaths (HR, 0.83 [95% CI, 0.51\u0026ndash;1.34]; k\u0026thinsp;=\u0026thinsp;12; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.44) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The cumulative forest plot by publication year is reported in \u003cb\u003eSupplementary Fig.\u0026nbsp;2\u003c/b\u003e. When stratified by specified follow-up times (\u003cb\u003eSupplementary Figs.\u0026nbsp;4A, 4C, and 4D\u003c/b\u003e), an association was observed between ECT receipt and reduced risk of suicide at 3 months (HR\u0026thinsp;=\u0026thinsp;0.53 [95% CI 0.39, 0.72]; k\u0026thinsp;=\u0026thinsp;4; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (\u003cb\u003eSupplementary Fig.\u0026nbsp;4B\u003c/b\u003e) but not at 1 month (k\u0026thinsp;=\u0026thinsp;2), 6 months (k\u0026thinsp;=\u0026thinsp;3), or 12 months (k\u0026thinsp;=\u0026thinsp;8).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eModerator analysis\u003c/h2\u003e \u003cp\u003eWe explored potential moderating roles of the following variables using meta-regression (for continuous measures) or meta-ANOVA (for binary or categorical measures) models: study sample size; type of relative risk (i.e., HR, OR, or RR); age; female sex (%); follow-up duration; diagnosis; and country of study. Female sex had a statistically significant but very small moderating effect, with females experiencing a slightly smaller ECT effect on mortality. For all-cause mortality as an outcome of interest, we identified country of study as a potential moderator of outcomes (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Each country has reported a lower risk of all-cause mortality, but the effect sizes vary by country. Japan had the largest effect size (HR\u0026thinsp;=\u0026thinsp;0.17, 95% CI 0.04 to 0.72; k\u0026thinsp;=\u0026thinsp;1) and Denmark had the smallest (HR\u0026thinsp;=\u0026thinsp;0.87, 95% CI 0.83 to 0.92, k\u0026thinsp;=\u0026thinsp;2). We have also reported the findings of moderator analysis for all-cause mortality by the follow-up period in \u003cb\u003eSupplementary Table\u0026nbsp;3\u003c/b\u003e. The number of patients enrolled in the component studies was considered a potential moderator of suicide deaths (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). We have also reported the findings of moderator analysis for suicide deaths by the follow-up period in \u003cb\u003eSupplementary Table\u0026nbsp;4\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eModeration analyses of all-cause mortality in ECT\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerator\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003ek\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCoefficient (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHazard ratio (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of total patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00 (-0.00 to 0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.915\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome measure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHazard ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.65 (0.54\u0026ndash;0.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.081\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOdds ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.87 (0.73\u0026ndash;1.03)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRelative risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.72 (0.46\u0026ndash;1.12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01 (-0.01 to 0.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.269\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e65 or older only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01 (-0.01 to 0.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.238\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.01 (-0.01 to -0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.036\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow-up duration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.05 (-0.01 to 0.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.125\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCondition\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e% major depressive disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00 (-0.02 to 0.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.985\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e% psychotic depression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01 (-0.00 to 0.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.223\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e% bipolar disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.00 (-0.02 to 0.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.506\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e% psychosis or schizophrenic spectrum disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.01 (-0.02 to 0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.155\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited States\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.52 (0.32\u0026ndash;0.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e0.002\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCanada\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.75 (0.58\u0026ndash;0.97)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSweden\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.67 (0.55\u0026ndash;0.82)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDenmark\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.87 (0.83\u0026ndash;0.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.17 (0.04\u0026ndash;0.72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTaiwan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.66 (0.46\u0026ndash;0.94)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eModeration analyses of suicide in ECT\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerator\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003ek\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCoefficient (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHazard ratio (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of total patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00 (0.00\u0026ndash;0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome measure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHazard ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.77 (0.40\u0026ndash;1.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.225\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOdds ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.38 (0.95\u0026ndash;2.01)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRelative risk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.70 (0.21\u0026ndash;2.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01 (-0.05 to 0.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.858\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e65 or older only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01 (-0.01 to 0.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.340\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.00 (-0.02 to -0.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.639\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow-up duration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.10 (-0.10 to 0.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.312\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCondition\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e% major depressive disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.02 (-0.04 to 0.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.233\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e% psychotic depression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.01 (-0.03 to 0.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.170\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e% bipolar disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.01 (-0.00 to 0.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.149\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e% psychosis or schizophrenic spectrum disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-0.00 (-0.21 to 0.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.997\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited States\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.58 (0.29\u0026ndash;1.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.251\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCanada\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.53 (0.31\u0026ndash;0.91)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSweden\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.72 (0.52-1.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDenmark\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.27 (0.63\u0026ndash;8.26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTaiwan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.80 (0.65\u0026ndash;0.99)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eMethodological quality and publication bias\u003c/h2\u003e \u003cp\u003eMethodological quality of the included studies and our justification were provided in \u003cb\u003eSupplementary Table\u0026nbsp;5\u003c/b\u003e in the Supplement. Studies published after 2005 were considered \u0026lsquo;\u003cem\u003egood\u003c/em\u003e,\u0026rsquo; and studies published in the 1980\u0026rsquo;s or earlier were considered \u0026lsquo;\u003cem\u003epoor\u003c/em\u003e\u0026rsquo; to \u0026lsquo;\u003cem\u003efair\u003c/em\u003e.\u0026rsquo; Only one study\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e was a randomized controlled trial, where the risk of bias was considered \u0026lsquo;\u003cem\u003elow\u003c/em\u003e.\u0026rsquo; In our main analysis, we did not find any potential publication bias for all-cause mortality as the primary outcome of interest (\u003cb\u003eSupplementary Fig.\u0026nbsp;5\u003c/b\u003e), using Egger\u0026rsquo;s test (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.10) and Begg and Mazumdar\u0026rsquo;s test (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.14). For suicide deaths as the outcome of interest (\u003cb\u003eSupplementary Fig.\u0026nbsp;6\u003c/b\u003e), we did not find any potential publication bias using Egger\u0026rsquo;s test (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.50) and Begg and Mazumdar\u0026rsquo;s test (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.89).\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this meta-analysis comprising over 41,000 patients that received ECT, it was determined that ECT was associated with a reduction in risk of all-cause mortality, a finding that was consistent at 3 months, 6 months, and 12 months of follow-up. Sex demonstrated a statistically significant but very small moderating effect on this relationship, with ECT being slightly less protective against all-cause mortality risk for females compared to males. Country also had a moderating effect. Each country has reported a lower risk of all-cause mortality associated with ECT, but the effect sizes vary by country. Japan had the largest effect size whereas Denmark had the smallest. ECT was associated with a reduction in suicide risk at 3 months of follow-up but not at 1, 6, or 12 months of follow-up.\u003c/p\u003e \u003cp\u003eThe findings of this meta-analysis suggest a treatment effect whereby ECT reduces the risk of all-cause mortality. Possible mechanisms whereby ECT may have a causal protective effect on mortality include both psychological/functional and biological mechanisms. With respect to a psychological/functional mechanism, one potential way in which ECT might lead to reduction in all-cause mortality risk is that ECT may help improve functioning, allowing patients to better engage in treatment for whatever medical conditions they face or maintain a healthier lifestyle. This is supported by a prior report wherein ECT recipients were less likely to die from a variety of causes, including smoking-related causes, cancer, circulatory diseases, and diabetes.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e With respect to potential biological mechanisms, ECT has been shown to reduce markers of neurodegeneration, and may also help improve innate immune functioning in individuals with depression.\u003csup\u003e\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e Successful treatment of mental illness may also normalize pathological vascular states that have been linked to mood disorders.\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eGiven that most studies included in this meta-analysis were observational in nature, the possibility that confounding explains this association must be considered.\u003csup\u003e\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e It is possible that patients with severe medical illness are not selected for ECT because of the risk of the procedure. We judge that confounding cannot account for the whole of the association between ECT and reduced mortality risk. One such reason is because many of the more recent, methodologically sophisticated longitudinal studies show a substantial difference between ECT and non-ECT groups in terms of mortality risk after carefully balancing known medical comorbidities. For instance, Kaster et al., conducted an assessment in which each of a range of 25 serious medical conditions were matched between the groups with a standardized mean difference of 0.02 or less.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e Rhee et al., conducted a sub-analysis wherein patients who received a subtherapeutic course of ECT (defined to be 4 treatments or fewer) were compared to those receiving a therapeutic course and those who did not receive ECT.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e The trajectory of mortality risk of those receiving a subtherapeutic course of ECT matched those who did not receive ECT for the first 6 months following hospital discharge (both of these groups were at greater risk of mortality compared to the therapeutic ECT group).\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Hence, while confounding may explain some of the observed association between ECT utilization and lower risk of all-cause mortality, several lines of evidence suggest that confounding does not explain all of the association.\u003c/p\u003e \u003cp\u003ePrevious studies on the possible effects of ECT on suicide have been inconsistent.\u003csup\u003e\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e\u003c/sup\u003e Notably, treatment guidelines from the American Psychiatric Association as well as the Canadian Network for Mood and Anxiety Treatments recommend the use of ECT for those with acute suicidal ideation.\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e The current meta-analysis did not find a consistent relationship between ECT and suicide risk. Notably, for those studies (k\u0026thinsp;=\u0026thinsp;4) that specifically reported outcomes 3 months after index date, a significant association was found between ECT receipt and reduced risk of suicide death. No association was found at months 1 (k\u0026thinsp;=\u0026thinsp;2), 6 (k\u0026thinsp;=\u0026thinsp;3), or 12 (k\u0026thinsp;=\u0026thinsp;8). Possibile explanations include discrepancies in power (for 1- and 6-month outcomes) and/or that any protective effect of ECT against suicide wanes beyond 3 months, especially if patients do not continue to receive continuation/maintenance therapy. It has long been shown that relapse rates are quite high (84%) among ECT responders by 6 months if no continuation/maintenance therapy is initiated.\u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOur analysis suggested that the association between ECT and all-cause mortality is slightly weaker for females than for males (standardized beta coefficient, -0.01). The significance of this finding is uncertain and, to our knowledge, has not been reported previously. This analysis also showed that country also had a moderating effect. Each country has reported a lower risk of all-cause mortality associated with ECT, but the effect sizes vary by country. The significance of this is unknown. Of note, all countries except the United States only had two or fewer studies.\u003c/p\u003e \u003cp\u003eSeveral limitations of the current study require comment. As noted, confounding cannot be entirely ruled out, as most studies included in this meta-analysis were non-randomized. Additionally, as is usually the case in meta-analyses, studies varied in the way outcomes were reported. This resulted in small numbers of studies for time-specific outcomes (k\u0026thinsp;=\u0026thinsp;2, for ECT and suicide association at 1 month). Furthermore, most studies did not report on what types of treatment were received at the conclusion of the index course of ECT. It has long been noted that the type of continuation/maintenance therapy can have a large bearing on clinical outcomes.\u003csup\u003e\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e,\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eECT is strongly associated with a reduced risk of all-cause mortality. This finding is seen internationally, across age groups and sexes. While confounding cannot be entirely ruled out due to most studies being non-randomized, recent large and high-quality studies that controlled for many measures of medical comorbidity affirmed this finding. ECT is not consistently associated with a reduced risk of suicide.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgement and disclosures\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eStudy approval statement\u003c/u\u003e\u003c/em\u003e:An ethics statement is not applicable because this study is based exclusively on published literature.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eConsent to participate statement\u003c/u\u003e\u003c/em\u003e: Written informed consent was not required as this study is based exclusively on published literature.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eData availability statement\u003c/u\u003e\u003c/em\u003e: Data are publicly available. All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eAuthor contributions\u003c/u\u003e\u003c/em\u003e: Study concept and design: TGR; Data acquisition and statistical analyses: TGR \u0026amp; SRS; Interpretation of data: TGR, SRS, MN, RSM, TSK, \u0026amp; STW; Drafting of manuscript: TGR, SRS, MN, \u0026amp; STW; Critical revision of manuscript for important intellectual content: TGR, SRS, MN, RSM, TSK, \u0026amp; STW; Supervision: TGR \u0026amp; STW. TGR and SRS are co-first authors. TGR had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eRole of the funder/sponsor\u003c/u\u003e\u003c/em\u003e: This study was not funded.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eConflict of interest disclosures\u003c/u\u003e\u003c/em\u003e: Each author completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and had none directly related to this manuscript.\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003e\u003cstrong\u003eRhee\u003c/strong\u003e was supported in part by the National Institute on Aging (NIA) (#R21AG070666; R21AG078972), National Institute of Mental Health (#R21MH117438), National Institute on Drug Abuse (#R21DA057540) and Institute for Collaboration on Health, Intervention, and Policy (InCHIP) of the University of Connecticut. Dr. Rhee serves as a review committee member for Patient-Centered Outcomes Research Institute (PCORI) and Substance Abuse and Mental Health Services Administration (SAMHSA) and has received honoraria payments from PCORI and SAMHSA. Dr. Rhee has also served as a stakeholder/consultant for PCORI and received consulting fees from PCORI. Dr. Rhee serves as an advisory committee member for International Alliance of Mental Health Research Funders (IAMHRF).\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"2\"\u003e\n \u003cli\u003e\u003cstrong\u003eShim\u003c/strong\u003e reported none.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"3\"\u003e\n \u003cli\u003e\u003cstrong\u003eNasir\u003c/strong\u003e reported none.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"4\"\u003e\n \u003cli\u003e\u003cstrong\u003eMcIntyre\u003c/strong\u003e has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC); speaker/consultation fees from Lundbeck, Janssen, Alkermes, Mitsubishi, Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk,Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie, Atai Life Sciences.\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"5\"\u003e\n \u003cli\u003e\u003cstrong\u003eKaster\u003c/strong\u003e is supported by the Canadian Institute for Health Research, the AFP Innovation Fund, and the Patient-Centered Outcomes Research Institute.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eWilkinson\u003c/strong\u003e reported receiving funding from Sage Therapeutics and Oui Therapeutics for the conduct of clinical trials (administered through Yale University) and personal fees from LivaNova and Mind Medicine outside the submitted work.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eThis study was not funded.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWorld Health Organization. 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Research Support, Non-U.S. Gov't. \u003cem\u003eJournal of Clinical Psychiatry\u003c/em\u003e. 04 13 2022;83(3):13. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://dx.doi.org/10.4088/JCP.21m13886\u003c/span\u003e\u003cspan address=\"10.4088/JCP.21m13886\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"depression, major depressive disorder, electroconvulsive therapy, ECT, suicide, suicide attempt ","lastPublishedDoi":"10.21203/rs.3.rs-6180102/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6180102/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eElectroconvulsive therapy (ECT) is among the most effective treatments for mood disorders and other psychotic disorders. This study meta-analyzed the effects of ECT on all-cause mortality and suicide deaths using longitudinal studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003ePubMed/MEDLINE, PsycINFO, Cochrane Library, Embase, and Google Scholar were searched from inception through January 21, 2025, with no language limits. Inclusion criteria were as follow: (1) patients with diagnoses of mental disorders; (2) intervention consisted of ECT compared with placebo, usual care or another intervention; (3) all-cause mortality and suicide deaths as outcome measures; and (4) clinical trial or longitudinal cohort study designs where the aforementioned interventions preceded the observations of outcome measures. Adjusted hazard ratio [HR] with their corresponding 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. Moderator analyses were also performed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eOverall, 17 studies consisting of 1,182,501 individuals (n=40,867 for ECT, n=1,141,634 for those receiving comparable interventions) were included. ECT was associated with a reduction in risk of all-cause mortality (HR, 0.70 [95% CI, 0.61-0.81]; \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001), a finding that was consistent at 3 months, 6 months, and 12 months of follow-up. Sex demonstrated a very small moderating effect on this relationship, with ECT being slightly less protective against mortality risk for females compared to males (standardized beta coefficient, -0.01 [-0.01 to 0.00]; \u003cem\u003ep\u003c/em\u003e=0.036). Regions also had a moderating effect (\u003cem\u003ep\u003c/em\u003e=0.002). Japan had the largest effect size (HR, 0.17 [0.04-0.72]) and Denmark had the smallest (HR, 0.87 [0.83-0.92]). ECT was associated with a reduction in suicide risk at 3 months of follow-up (HR, 0.53 [0.39-0.72]; \u003cem\u003ep\u003c/em\u003e\u0026lt;0.001) but not at 1, 6, or 12 months of follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eECT is associated with a reduced risk of all-cause mortality. ECT, however, was not consistently associated with a reduced risk of suicide.\u003c/p\u003e","manuscriptTitle":"Longitudinal Associations of Electroconvulsive Therapy with All-cause Mortality and Suicide Deaths in Depression and Other Psychiatric Disorders: A Systematic Review and Meta-Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-31 08:57:54","doi":"10.21203/rs.3.rs-6180102/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3b3f0dac-00c9-48e3-8620-14be416bec21","owner":[],"postedDate":"March 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":45873137,"name":"Health sciences/Diseases/Psychiatric disorders/Depression"},{"id":45873138,"name":"Health sciences/Diseases/Psychiatric disorders/Bipolar disorder"}],"tags":[],"updatedAt":"2025-07-02T15:26:54+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-31 08:57:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6180102","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6180102","identity":"rs-6180102","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}