Ketamine or ECT? What Have We Learned From the KetECT and ELEKT-D Trials?

1. Two recent clinical trials, KetECT and ELEKT-D, compared the effectiveness of ketamine and electroconvulsive therapy (ECT) for major depressive disorder. Notably, these trials reported marked differences in ECT's clinical outcomes of, with remission rates of 63% for KetECT and a strikingly lower rate of 22% for ELEKT-D, while the remission rates for ketamine were 46% and 38%, respectively. Considering that the primary objective of both trials was to compare the standard treatment (ECT) with an experimental intervention (ketamine), it is crucial to highlight the pronounced disparities in ECT's clinical outcomes. This article offers a comprehensive comparison of these trials while also exploring how patient characteristics, treatment protocols, and study designs may contribute to such pronounced outcome discrepancies. These differences highlight the heterogeneous nature of depression and underscore the need for personalized treatments. These studies also provide valuable insights into identifying the most suitable candidates for ketamine and ECT.

Antipsychotics in the maintenance phase for psychotic depression.

OBJECTIVE: This study aimed to associate antidepressants with versus without antipsychotics with readmission and suicide in patients with psychotic unipolar depression. METHODS: Swedish national registers were used to identify inpatients with psychotic unipolar depression, treated 2007-2016. The participants collected antidepressants with or without antipsychotics from a pharmacy within 14 days after discharge and were followed up for 2 years. The primary outcome was hospital readmission due to any psychiatric disorder, suicide attempt, or completed suicide. Cox regression was used to analyze the data, which were adjusted for sex, age, prior admissions, comorbidity, electroconvulsive therapy, and other pharmacological treatments. RESULTS: We identified 4391 patients, of which 2972 were in the antidepressant + antipsychotic combination therapy group, and 1419 were in the antidepressant monotherapy group. After 2 years, 42.3% and 36.6% of patients were readmitted or committed suicide in the combination therapy and monotherapy group, respectively. Monotherapy was significantly associated with a lower risk of reaching the outcome in the main analysis (hazard ratio = 0.86; 95% confidence interval: 0.77-0.95). The results went in the same direction in all sensitivity analyses. CONCLUSION: Our findings do not indicate any advantage of adding antipsychotics as adjunctive to antidepressants as maintenance treatment. Considering the wide use, known side effects, and the current lack of evidence supporting the benefit, further studies on the effect of antipsychotics in the maintenance phase of psychotic unipolar depression are urgently warranted.

Electroconvulsive therapy in the maintenance phase of psychotic unipolar depression.

OBJECTIVE: To determine whether the rates of readmissions and suicide vary in psychotic unipolar depression based on whether patients receive maintenance electroconvulsive therapy (M-ECT) following the initial series of ECT, and to examine if there is an age-dependent association. METHODS: We used Swedish national registries to identify hospitalized patients with psychotic unipolar depression, treated 2008-2019 who received ECT during their hospital stay. The patients who received subsequent M-ECT within 14 days after discharge were compared with those who did not. The primary composite outcome was time to readmission due to a psychiatric disorder, suicide attempt, or suicide within 2 years from discharge. Data were analyzed using Cox regression adjusted for previous psychiatric admissions, age, sex, comorbidity, and pharmacological treatment. We also conducted a within-individual analysis using the sign-test, with patients having ≥1 hospital episode followed by M-ECT and ≥1 hospital episode without M-ECT. RESULTS: A total of 1873 patients were included, of which 130 received M-ECT. There was no statistically significant group difference regarding the primary outcome in the whole sample. However, when stratified by age, there was a significant difference in favor of M-ECT for patients >65 years (adjusted hazard ratio 0.55, 95% confidence interval 0.35-0.87). The within-individual analysis, including 46 patients, significantly favored M-ECT. CONCLUSION: M-ECT was not associated with a differential risk of the composite of readmission and suicide in psychotic depression. Among patients >65 years, M-ECT was significantly associated with a decreased risk of the outcome. The possibility of residual confounding cannot be excluded.

Association between electroconvulsive therapy and time to readmission after a manic episode.

OBJECTIVE: The majority of patients hospitalized for treatment of a manic episode are readmitted within 2 years despite maintenance treatment. Electroconvulsive therapy (ECT) has been associated with lower rehospitalization rates in some psychiatric conditions, but its association with readmission after a manic episode has not been investigated. Therefore, the aim of this study was to determine whether the time to readmission in patients with mania treated with ECT was longer than in patients not treated with ECT and whether there were subgroups of patients that benefited more. METHODS: This was a nationwide register-based, observational study. All patients diagnosed with bipolar disorder, manic episode, admitted to any hospital in Sweden between 2012 and 2021 were included. Patients contributed data to the study for every admission. All admissions were followed up until psychiatric readmission, death, or the end of the study (December 31, 2021). Association between ECT and time to readmission was analyzed. A paired samples model was performed for 377 patients with at least two admissions for mania, treated with ECT at one admission and without ECT at the other admission. Times to readmission were analyzed. RESULTS: A total of 12,337 admissions were included; mean (SD) age 47.7 (17.2), 5443 (44.1%) men. Readmission rate within 1 year was 54.6%. ECT was administered in 902 (7.3%) admissions. Within 30 days after admission, 182 out of 894 (20.4%) patients treated with ECT versus 2105 out of 11,305 (18.6%) patients treated without ECT were readmitted. There was no association between ECT and time to readmission (aHR 1.00, 95% CI 0.86-1.16, p = 0.992) in the model with all admissions. The paired samples model included 754 admissions (377 patients), mean (SD) age during admission without ECT was 45.6 (16.5), and with ECT 46.6 (16.4), 147 (39.0%) were men. In that model, readmission rate within 30 days for treatment with ECT was 19.0%, and for treatments without ECT, 24.1% (aHR 0.75, 95% CI 0.55-1.02, p = 0.067). CONCLUSION: Readmission rates after inpatient treatment of mania were high. ECT was not significantly associated with longer time to readmission, but there was a trend toward a protective effect of ECT when admissions with and without ECT were compared within the same patients.

Suicidal behavior and all-cause mortality in depressed older adults aged 75+ treated with electroconvulsive therapy: A Swedish register-based comparison study.

OBJECTIVES: Electroconvulsive therapy (ECT) is effective in treating late-life depression. There is limited research on suicidal behavior and all-cause mortality in the oldest old after ECT. METHODS: Older adults aged 75 years and above who had been inpatients for moderate to severe depression between January 1, 2011, and December 31, 2017, were included in the study. We used exact and propensity score matching to balance groups. We compared suicidal behavior (fatal and non-fatal) and all-cause mortality in those who had received ECT and those with other depression treatments. RESULTS: Of the study population, 1802 persons who received ECT were matched to 4457 persons with other treatments. There were no significant differences in the risk of suicidal behavior between groups, (within 3 months: odds ratio 0.73; 95% confidence intervals (CI), 0.44-1.23, within 4 months to 1 year: aOR 1.34; 95% CI, 0.84-2.13). All-cause mortality was lower among ECT recipients compared to those who had received other treatments, both within 3 months (aOR, 0.35; 95% CI, 0.23-0.52), and within 4 months to 1 year (aOR 0.65; 95% CI, 0.50-0.83). CONCLUSIONS: Compared to other depression treatments, ECT is not associated with a higher risk of suicidal behavior in patients aged 75 and above. ECT is associated with lower all-cause mortality in this age group, but we advise caution regarding causal inferences.

Long-Term Effect of Maintenance Electroconvulsive Therapy in Patients With Depression-Data From a Small Randomized Controlled Trial.

OBJECTIVES: This study aimed to compare the long-term effects of maintenance electroconvulsive therapy (M-ECT) with medication and medication only in patients with depression. METHODS: A randomized controlled trial of 1 year of M-ECT with medication or medication only investigated relapse/recurrence among 56 patients in remission after electroconvulsive therapy (ECT) for depression was conducted. The results of the first year are published already and showed a significant advantage of M-ECT with medication.The current study was a long-term follow-up. When the randomized treatment allocation ended, medication was continued in both groups but M-ECT was terminated. Patients were followed for up to 10 years via Swedish national registers until the study endpoint of a new psychiatric diagnosis as an inpatient, suicide, suspected suicide, or death of another cause. Time to relapse was compared between the M-ECT with medication group and the medication-only group using Kaplan-Meier estimates. RESULTS: The median follow-up time was 6.5 years for the M-ECT and medication group and 3.1 years for the medication-only group. One year after randomization 22 patients remained in the M-ECT and medication group, and 14 patients remained in the medication-only group. Relapse patterns between the treatment groups after the completion of M-ECT seemed to be similar according to visual inspection. CONCLUSIONS: This long-term follow-up study suggests that most of the benefit achieved during the treatment period with M-ECT is maintained over several years, but the small sample size, with accompanying large statistical imprecision, makes the results uncertain. More long-term studies of M-ECT are required.Trial registration: ClinicalTrials.gov identifier: NCT00627887.

Association between pulse width and health-related quality of life after electroconvulsive therapy in patients with unipolar or bipolar depression: an observational register-based study.

AIMS: To examine the association between pulse width and HRQoL measured within one week after electroconvulsive therapy (ECT) and at six-month follow-up in patients with unipolar or bipolar depression. METHODS: This was an observational register study using data from the Swedish National Quality Registry for ECT (2011-2019). Inclusion criteria were: age ≥18 years; index treatment for unipolar/bipolar depression; unilateral electrode placement; information on pulse width; EQ-5D measurements before and after ECT. Multiple linear regressions were performed to investigate the association between pulse width (<0.5 ms; 0.5 ms; >0.5 ms) and HRQoL (EQ-5D-3L index; EQ VAS) one week after ECT (primary outcome) and six months after ECT (secondary outcome). RESULTS: The sample included 5,046 patients with unipolar (82%) or bipolar (18%) depression. At first ECT session, 741 patients (14.7%) had pulse width <0.5 ms, 3,639 (72.1%) had 0.5 ms, and 666 (13.2%) had >0.5 ms. There were no statistically significant associations between pulse width and HRQoL one week after ECT. In the subsample of patients with an EQ-5D index recorded six months after ECT (n = 730), patients receiving 0.5 ms had significantly lower HRQoL (-0.089) compared to <0.5 ms, after adjusting for demographic and clinical characteristics (p = .011). The corresponding analysis for EQ VAS did not show any statistically significant associations. CONCLUSION: No robust associations were observed between pulse width and HRQoL after ECT. On average, significant improvements in HRQoL were observed one week and six months after ECT for patients with unipolar or bipolar disease, independent of the pulse width received.

Safety of and response to electroconvulsive therapy during pregnancy: Results from population-based nationwide registries.

INTRODUCTION: Psychiatric disorders are common during pregnancy, affecting up to 16% of pregnant women. Severe depression and anxiety have significant negative effects on the health of both the mother and the developing fetus. Electroconvulsive therapy (ECT) is considered a treatment option for pregnant women with severe psychiatric disorders when other treatments have been ineffective or pose risks to the fetus. Knowledge of the safety and efficacy of ECT during pregnancy, however, remains limited. METHODS: Data were obtained from nationwide registries of pregnant women in Sweden who received ECT for a severe psychiatric disorder from January 2008 to December 2021. ECT-related outcomes in pregnant women were compared by propensity score matching with a group of non-pregnant women who also received ECT. Pregnancy-related outcomes were compared with two additional control groups: one consisting of the same group of women who did not receive ECT during another pregnancy and the other composed of pregnant women admitted to inpatient psychiatric care but who did not receive ECT, matched based on propensity score. RESULTS: Ninety-five pregnant women received ECT during the study period, accounting for 97 pregnancies. The response rate to ECT in pregnant women (n = 54) was similar to the matched control group of non-pregnant women (74% vs. 65%; OR 1.61; 95% CI 0.79-3.27). Rates of adverse events related to ECT were similar to those in the control group. There were no pre-term births or severe adverse outcomes related to the pregnancy, that were close in time to ECT. Therefore, no adverse outcomes related to pregnancy and childbirth could be directly attributed to ECT. The likelihood of premature birth and a 5-min Apgar score <7 in the newborn were both significantly higher in the ECT group, compared with the matched non-ECT group (OR 2.33, 95% CI 1.15-4.73, p = 0.008, and OR 3.68, 95% CI 1.58-8.55, p < 0.001, respectively). By contrast, no significant differences were observed when women in the pregnant ECT group were compared with the same group lacking ECT during another pregnancy. CONCLUSIONS: ECT was associated with a positive treatment response in pregnant women with severe psychiatric disorders. The response rate to ECT was similar in pregnant and non-pregnant women. Nevertheless, the risks of premature birth and of a slightly poorer condition in newborns were higher in women who did than did not receive ECT, emphasizing the need for increased attention to severe psychiatric disorders during pregnancy.

Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits).

BACKGROUND: The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance. The primary objective of this study is to test whether the monoclonal antibody rituximab, directed against the B-cell antigen CD20 ameliorates psychotic symptoms in adults with schizophrenia or schizoaffective disorder and to examine potential mechanisms. A secondary objective is to examine characteristics of inflammation-associated psychosis and to identify pre-treatment biochemical characteristics of rituximab responders. A third objective is to interview a subset of patients and informants on their experiences of the trial to obtain insights that rating scales may not capture. METHODS: A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of B-cell depletion in patients with psychosis. 120 participants with a diagnosis of schizophrenia spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion of rituximab (1000 mg) or saline. Psychiatric measures and blood samples will be collected at baseline, week 12, and week 24 post-infusion. Brief assessments will also be made in weeks 2 and 7. Neuroimaging and lumbar puncture, both optional, will be performed at baseline and endpoints. Approximately 40 of the patients and their informants will be interviewed for qualitative analyses on the perceived changes in well-being and emotional qualities, in addition to their views on the research. DISCUSSION: This is the first RCT investigating add-on treatment with rituximab in unselected SSD patients. If the treatment is helpful, it may transform the treatment of patients with psychotic disorders. It may also heighten the awareness of immune-psychiatric disorders and reduce stigma. TRIAL REGISTRATION: NCT05622201, EudraCT-nr 2022-000220-37 version 2.1. registered 14th of October 2022.

Electroconvulsive therapy in children and adolescents: results from a population­based study utilising the Swedish National Quality Register.

Electroconvulsive therapy (ECT) is effective and safe for adults with severe depression, but less studied in adolescents. Here, we examined the indications, prevalence, practice, response and remission rates, and side effects in young people treated with ECT in Sweden. We also examined the usage of ECT in the transition to adult psychiatry. Using data from national patient registers and the Swedish National Quality Register for ECT (Q-ECT), we identified patients aged up to 19 years treated with ECT over a 5-year study period. Response and remission rates were analysed using the Clinical Global Impression (7-point scale)-Improvement (CGI-I) and Severity (CGI-S). A total of 118 individuals were identified, of which 105 were also enrolled in the Q-ECT. The most common indication for ECT was depression (68%; n = 80). Adolescents aged < 18 years were more severely ill before treatment than those aged 18 years (P < 0.01). Three of the hospitals in Sweden treated the majority of adolescents < 18 years old. The median number of sessions in each ECT series was seven. Unilateral placement of the electrodes was the most common (88%; n = 99). Fifty-seven percent (n = 54) of the patients responded (CGI-I, 1-2) to the treatment; remission (CGI-S, 1-2) was achieved by 32% (n = 30). Psychotic symptoms were associated with a higher response rate in patients with depression (P = 0.038). A deterioration of memory compared to pre-treatment was reported in six patients. ECT was associated with high response and remission rates in adolescents with severe psychiatric disorders after non-response to medication.

Electroconvulsive Therapy Versus Repetitive Transcranial Magnetic Stimulation in Patients With a Depressive Episode: A Register-Based Study.

OBJECTIVES: Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) are both effective in treating depression. Although rTMS induces fewer adverse effects, its effectiveness relative to ECT is not well established. The aim of this study was to investigate the treatment outcomes of ECT and rTMS in patients who have received both interventions. METHODS: This was a register-based observational crossover study in patients with depression who had undergone ECT and rTMS in Sweden between 2012 and 2021. Primary outcome was reduction in the Montgomery-Åsberg Depression Rating Scale-Self-report (MADRS-S) score. Secondary outcome was response defined as a 50% or greater decrease in the MADRS-S score. Subgroup analyses were performed to identify factors that predicted differential responses between rTMS and ECT. Continuous and categorical variables were analyzed using paired-samples t tests and McNemar tests, respectively. RESULTS: In total, 138 patients across 19 hospitals were included. The MADRS-S score after ECT and rTMS was reduced by 15.0 and 5.6 (P = 0.0001) points, respectively. Response rates to ECT and rTMS were 38% and 15% (P = 0.0001), respectively. Electroconvulsive therapy was superior across all subgroups classified according to age and severity of depression. CONCLUSIONS: Our results suggest that ECT is more effective than rTMS in treating depression among patients who have received both interventions. Age and baseline depression severity did not predict who would similarly benefit from rTMS and ECT.

Validity of the self-rated 36-item World Health Organization Disability Assessment Schedule (WHODAS) 2.0 as a measure of functioning in Swedish psychiatric outpatients.

PURPOSE: The aim of this study was to investigate concurrent validity of the Swedish self-rated 36-item World Health Organization Disability Assessment Schedule (WHODAS) 2.0 by comparison with professional Global Assessment of Functioning (GAF) ratings in psychiatric outpatients. MATERIAL AND METHODS: A cross-sectional convenience sample of 444 patients was recruited from their regular psychiatric outpatient settings. The patients filled out the WHODAS 2.0; their clinicians provided clinical information and performed GAF ratings blinded to the patients' assessments. Analyses of correlations, variance components, and ROC curves were performed to investigate the validity of the WHODAS 2.0 through comparison with the GAF. The variance component analyses included working status, psychosocial problems, number of diagnostic groups, and remission status. GAF ratings were separated as total (GAF-T), symptoms (GAF-S), and functioning (GAF-F). RESULTS: There was significant correlation (p < 0.001) between WHODAS 2.0 total and domain scores and GAF-S, GAF-F, and GAF-T ratings. The correlations varied from r = 0.29 to r = 0.48, with the highest being between GAF-F rating and WHODAS 2.0 total score. Repeating the analyses for separate diagnostic groups replicated the findings, though not for psychotic, substance-related, and eating disorders. The WHODAS 2.0 showed good ability to distinguish impaired functioning below a fixed GAF-T cut-off of 70 (area under the curve: 0.74-0.78). The explained variance was lower for the WHODAS 2.0 than for the GAF (38.9% vs. 59.2%). CONCLUSIONS: Concurrent validity was found when comparing the Swedish self-administered 36-item version of WHODAS 2.0 with the expert-rated GAF in psychiatric outpatients.

Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression: A Randomized, Open-Label, Non-Inferiority Trial (KetECT).

BACKGROUND: Ketamine has emerged as a fast-acting and powerful antidepressant, but no head to head trial has been performed, Here, ketamine is compared with electroconvulsive therapy (ECT), the most effective therapy for depression. METHODS: Hospitalized patients with unipolar depression were randomized (1:1) to thrice-weekly racemic ketamine (0.5 mg/kg) infusions or ECT in a parallel, open-label, non-inferiority study. The primary outcome was remission (Montgomery Åsberg Depression Rating Scale score ≤10). Secondary outcomes included adverse events (AEs), time to remission, and relapse. Treatment sessions (maximum of 12) were administered until remission or maximal effect was achieved. Remitters were followed for 12 months after the final treatment session. RESULTS: In total 186 inpatients were included and received treatment. Among patients receiving ECT, 63% remitted compared with 46% receiving ketamine infusions (P = .026; difference 95% CI 2%, 30%). Both ketamine and ECT required a median of 6 treatment sessions to induce remission. Distinct AEs were associated with each treatment. Serious and long-lasting AEs, including cases of persisting amnesia, were more common with ECT, while treatment-emergent AEs led to more dropouts in the ketamine group. Among remitters, 70% and 63%, with 57 and 61 median days in remission, relapsed within 12 months in the ketamine and ECT groups, respectively (P = .52). CONCLUSION: Remission and cumulative symptom reduction following multiple racemic ketamine infusions in severely ill patients (age 18-85 years) in an authentic clinical setting suggest that ketamine, despite being inferior to ECT, can be a safe and valuable tool in treating unipolar depression.

Genome-wide association study of patients with a severe major depressive episode treated with electroconvulsive therapy.

Although large genome-wide association studies (GWAS) of major depressive disorder (MDD) have identified many significant loci, the SNP-based heritability remains notably low, which might be due to etiological heterogeneity in existing samples. Here, we test the utility of targeting the severe end of the MDD spectrum through genome-wide SNP genotyping of 2725 cases who received electroconvulsive therapy (ECT) for a major depressive episode (MDE) and 4035 controls. A subset of cases (n = 1796) met a narrow case definition (MDE occurring in the context of MDD). Standard GWAS quality control procedures and imputation were conducted. SNP heritability and genetic correlations with other traits were estimated using linkage disequilibrium score regression. Results were compared with MDD cases of mild-moderate severity receiving internet-based cognitive behavioral therapy (iCBT) and summary results from the Psychiatric Genomics Consortium (PGC). The SNP-based heritability was estimated at 29-34% (SE: 6%) for the narrow case definition, considerably higher than the 6.5-8.0% estimate in the most recent PGC MDD study. Our severe MDE cases had smaller genetic correlations with neurodevelopmental disorders and neuroticism than PGC MDD cases but higher genetic risk scores for bipolar disorder than iCBT MDD cases. One genome-wide significant locus was identified (rs114583506, P = 5e-8) in an intron of HLA-B in the major histocompatibility locus on chr6. These results indicate that individuals receiving ECT for an MDE have higher burden of common variant risk loci than individuals with mild-moderate MDD. Furthermore, severe MDE shows stronger relations with other severe adult-onset psychiatric disorders but weaker relations with personality and stress-related traits than mild-moderate MDD. These findings suggest a different genetic architecture at the severest end of the spectrum, and support further study of the severest MDD cases as an extreme phenotype approach to understand the etiology of MDD.

Suicidal ideation and ECT, ECT and suicidal ideation: A register study.

OBJECTIVE: Although electroconvulsive therapy (ECT) is anti-suicidal, it is not known whether the presence of suicidal ideation (SI) at baseline predicts response and remission after ECT. The aim of the study was to analyze the impact of baseline SI on response and remission following ECT treatment in a large sample of patients with depression and to assess SI before and after ECT. METHODS: This population-based register study used data from the Swedish National Quality Register for ECT and the Swedish Patient Register. Patients aged 18 years or older who had received ECT for a unipolar or bipolar depressive episode between 2011 and 2018 were included in the study. SI was defined as a score of ≥4 on the last item of the Montgomery-Åsberg Depression Rating Scale - Self Assessment (MADRS-S). Using a logistic regression model, SI at baseline was used to predict response and remission following ECT, while controlling for depression severity, psychotic symptoms, presence of a comorbid personality disorder, age, sex, electrode position, unipolar or bipolar disorder, and number of previous suicide attempts at baseline. RESULTS: In patients who exhibited SI at baseline, 53.7% (N = 632) of cases showed a response to ECT, whereas 68.4% (N = 690) of patients without SI showed a response. In addition, 27.2% (N = 320) of cases with SI achieved remission, whereas 48.5% (N = 489) of cases without SI achieved remission. The odds of achieving response and remission for patients with SI were 0.75 and 0.58 times, respectively, those for patients without SI. Of the 1178 patients with pre-treatment SI, 75.64% (N = 891) exhibited no SI at the end of treatment. Moreover, in this subgroup, the presence of a personality disorder, higher MADRS-S-score, and younger age were associated with persistent SI. CONCLUSION: The presence of SI was associated with lower ECT response and remission rates. Nevertheless, depressive symptoms and SI were reduced in a large proportion of patients across both patient groups. Clinicians should be aware of the lower likelihood of achieving a successful outcome following ECT in younger patients who present with a non-psychotic depressive episode, SI, and (suspected) personality disorders. More research is warranted regarding if these patients can achieve similar or better results with other treatments.

A systematic review and meta-analysis of maintenance treatment for psychotic depression.

PURPOSE: To perform a systematic review on the use of maintenance treatment to prevent relapse and recurrence in patients with psychotic unipolar or bipolar depression. METHODS: We conducted an electronic search in December 2019 (and an updated search in July 2021) of four databases (PubMed, Embase, PsycINFO, and Cochrane) to identify controlled studies comparing the relapse rates of patients receiving maintenance treatment for psychotic unipolar depression and psychotic bipolar depression. A meta-analysis was made that included three studies comparing antidepressant (AD) and antipsychotic (AP) combination therapy with AD monotherapy. We used the GRADE tool to assess the quality of evidence. RESULTS: We included five randomized controlled trials fulfilling the inclusion criteria, making three comparisons: (a) AD + AP versus AD monotherapy; (b) AD + AP versus AP monotherapy; (c) AD + electroconvulsive therapy versus AD monotherapy. The included studies only examined patients with psychotic unipolar depression. The largest included study reported a statistically significant advantage of AD + AP compared with AD monotherapy. We made a meta-analysis of the three studies comparing AD + AP combination therapy with AD monotherapy, which included 195 patients and 56 events. The meta-analysis did not show a statistically significant difference between these treatments. CONCLUSIONS: Contrary to the finding of the largest study, we did not find a statistically significant difference between AD + AP combination therapy and AD monotherapy in the meta-analysis. There is insufficient evidence to support the superiority of any treatment modality as maintenance treatment for psychotic depression. Further studies are required.

Validity of diagnoses, treatment dates, and rating scales in the Swedish national quality register for electroconvulsive therapy.

BACKGROUND: The Swedish national quality register for electroconvulsive therapy (Q-ECT) contains data on patients receiving treatment with electroconvulsive therapy (ECT) in Sweden. AIM: This study determined the validity of diagnoses, treatment dates, and rating scales in the Q-ECT by investigating the degree of accordance between data from the Q-ECT and patient records. MATERIALS AND METHODS: From January 2016 to December 2017, 200 treatment series were randomly selected from the Q-ECT. The corresponding patient records were requested from the treating hospitals. Data on the indicative diagnosis, dates for the first and the last ECT session, and rating scales were compared between the Q-ECT and patient records using (i) a strict and (ii) a liberal method of assessment. Using the liberal method, each variable was assessed as accordant if it belonged to the same diagnosis group, or if the dates differed by less than 1 week, or ratings differed by only 1 point on the Clinical Global Impression Scale (CGI- S), or no more than 3 points on the Montgomery Åsberg Depression Rating Scale between the Q-ECT and the patient record. RESULTS: A total of 179 patient records were received. The strict method of assessment showed an accordance of 89% or higher for all studied variables. The liberal method showed an accordance of 95% or higher. CONCLUSIONS: We conclude that data on the studied variables in the Q-ECT have high validity. However, limited use of some rating scales makes the results uncertain. Measures can be taken to further improve the data quality.

Does lithium prevent relapse following successful electroconvulsive therapy for major depression? A systematic review and meta-analysis.

OBJECTIVE: The risk of relapse following successful antidepressant treatment, including electroconvulsive therapy (ECT), is substantial. Lithium has been suggested to effectively prevent relapse, yet data remain limited and inconclusive. We performed a systematic review and meta-analysis to examine the efficacy of continuation treatment with lithium in preventing relapse following a successful acute course of ECT in patients with major depression, in comparison to continuation treatment without lithium. We also assessed the role of several study characteristics, possibly impacting the treatment effect. METHODS: A systematic literature search, using the PubMed, Embase, Web of Science, and Cochrane Library databases (up to June 2020), was conducted for prospective and retrospective studies, including patients with unipolar or bipolar depression, that assessed the efficacy of lithium for post-ECT depressive relapse prevention. RESULTS: Of 2556 records screened, 14 articles reporting on 9748 participants who received continuation treatment either with (N = 1571) or without lithium (N = 8177) were included in the meta-analysis. Patients receiving lithium were less likely to experience depressive relapse after a successful acute course of ECT, compared to patients receiving post-ECT prophylaxis without lithium (weighted odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.34, 0.82), with a number needed to treat (NNT) of 7 (95% CI = 4, 21). We found some limited evidence that older patients may benefit more from continuation treatment with lithium, compared to younger patients. Using the GRADE criteria, the quality of evidence for our outcome measure (i.e., relapse rate) was rated as very low. CONCLUSION: Continuation treatment with lithium may have superior efficacy in reducing the risk of relapse after a successful acute ECT course for major depression, in comparison to continuation treatment without lithium. High-quality studies are needed to confirm this finding.

Electroconvulsive therapy and psychiatric readmission in major depressive disorder - A population-based register study.

OBJECTIVE: The primary aim was to determine whether electroconvulsive therapy (ECT) is associated with reduced risk of psychiatric readmission in major depressive disorder (MDD). METHODS: This study was based on data from multiple Swedish population-based registries. All adult patients admitted to any Swedish hospital for moderate-to-severe MDD between 2012 and 2018 were included. Participants were divided into two groups depending on whether they received ECT during inpatient care. Follow-up was set at 30 and 90 days from discharge. Data were analyzed using logistic regression, and matching was conducted. RESULTS: A total of 27,851 unique patients contributed to 41,916 admissions. ECT was used in 26.8% of admissions. In the main multivariate analysis, the risk of both 30- and 90-day readmission was lower in the ECT group than in the non-ECT group. In a matched sensitivity model, the results pointed in the same direction for readmission risk within 30 days, but statistical significance was not reached. ECT-treated subgroups with superior outcomes on readmission risk compared with non-ECT treatment were older, unemployed, married, or widowed patients, those treated with antipsychotics or benzodiazepines before admission, with psychotic features, prior psychiatric hospitalizations, or family history of suicide. However, in patients below 35 years of age, ECT was associated with increased readmission risk. CONCLUSION: This study suggests that ECT reduces the risk of psychiatric readmission in certain subgroups of patients with MDD. Since patients receiving ECT tend to be more difficult to treat, there is a risk of residual confounding.