Reliable Change Indices and Minimum Detectable Change for the Montreal Cognitive Assessment in Electroconvulsive Therapy for Depression.

OBJECTIVE: The Montreal Cognitive Assessment (MoCA) is a commonly used brief cognitive screening tool for monitoring adverse cognitive effects of electroconvulsive therapy (ECT). The aim of this study was to examine three statistical methods for detecting reliable change in the MoCA following ECT. METHODS: In a prospective cohort study, 47 patients (mean age 55.2 [SD = 12.8], 59.6% female) with unipolar or bipolar depression treated with an acute course of brief-pulse ECT (72.3% right unilateral) and 47 depressed controls without ECT exposure were tested on the MoCA at baseline and retested at comparable time intervals. ECT patients' performance was also compared to published normative data from a community-based sample of older adults. We calculated proportions of ECT patients remaining stable, declining, and improving following ECT using practice-corrected reliable change index, standardized regression-based formulas, and minimum detectable change cutoff of ±4 MoCA points. RESULTS: Using the three methods, 72.3%-78.7% of ECT patients remained stable, 17.0%-23.4% declined, and 4.3% improved in MoCA performance following ECT compared to the two control groups. CONCLUSIONS: All three methods yield consistent estimates of reliable change in MoCA scores from pre- to post-brief-pulse ECT. The minimum detectable change approach may be the most efficient and accessible method of detecting change due to simplicity of calculation.

Study protocol for Ketamine as an adjunctive therapy for major depression (2): a randomised controlled trial (KARMA-Dep [2]).

BACKGROUND: Depression is a common psychiatric disorder and a leading cause of disability worldwide. Conventional monoaminergic antidepressants have limited efficacy and take weeks to exert a therapeutic effect. Single infusions of subanaesthetic doses of ketamine exhibit rapid antidepressant action but effects are transient and relapse is common. One potential strategy for increasing ketamine's antidepressant efficacy and/or prolonging its therapeutic benefit may be serial infusions. There is limited evidence on the efficacy and safety of repeated ketamine infusions against an active comparator. METHODS: This protocol describes an ongoing pragmatic, randomised, controlled, parallel-group, patient- and rater-blind, superiority trial. Eligible adult inpatients with a confirmed DSM-5 diagnosis of a major depressive episode (unipolar or bipolar) are randomly allocated in a 1:1 ratio to a course of up to eight infusions of ketamine or midazolam twice-weekly over four weeks. The primary objective is to assess the efficacy of serial adjunctive ketamine infusions versus active comparator midazolam by measuring Montgomery-Åsberg Depression Rating Scale score difference between arms from before the first infusion to 24 h after the final infusion, supplemented by a 95% confidence interval. To facilitate generalisability of results, the trial takes place under "real world" conditions with both groups continuing to receive regular inpatient care including treatment-as-usual pharmacotherapy, nursing care, and psychological and other therapies during the randomised treatment phase and regular outpatient care thereafter. Participants are monitored for relapse during a 24-week follow-up after the end of the randomised phase. Secondary objectives of the trial are to assess: response and remission rates at the end of randomised phase; relapse status during the 24-week follow-up after the end of the randomised phase; the safety and tolerability of repeated ketamine infusions regarding psychotomimetic and other psychiatric side effects, cognitive side effects, as well as withdrawal symptoms, haemodynamic stability, neurological, urological, and other physical side effects; and quality of life and cost-effectiveness. DISCUSSION: There is an unmet clinical need for rapidly-acting novel antidepressants. This trial will provide efficacy, safety and health economic data on serial ketamine infusions and thus help inform clinical practice on the potential role of this treatment in the management of depression. TRIAL REGISTRATION: EudraCT 2019-003109-92. Registered 2 October 2019. CLINICALTRIALS: gov NCT04939649. Registered 25 June 2021.

Relapse following bitemporal and high-dose right unilateral electroconvulsive therapy for major depression.

OBJECTIVE: Electroconvulsive therapy (ECT) is an effective acute treatment for severe and/or medication-resistant depression but maintaining remission following completion of a course remains a clinical challenge. METHODS: EFFECT-Dep Trial (ISRCTN23577151) participants with a DSM-IV major depressive episode who met remission criteria after a randomly assigned course of twice-weekly brief-pulse bitemporal (1.5 × seizure threshold) or high-dose (6 × seizure threshold) right unilateral ECT were monitored for relapse for 12 months. In line with the pragmatic trial design, all patients received treatment-as-usual individualised pharmacotherapy during and after ECT; no remitter received continuation ECT. RESULTS: Of 61 remitters, 24 (39.3%) relapsed, one (1.6%) withdrew from the study while in remission and the remaining 36 (59.0%) stayed well for a year. Most relapses occurred within the first six months, resulting in a cumulative six-month relapse rate of 31.1%. In a multivariable Cox proportional hazards regression model, older age (p = 0.039) and psychotic features at pre-ECT baseline (p = 0.037) were associated with a more favourable long-term prognosis while a greater number of previous depressive episodes (p = 0.028) and bipolar II (but not bipolar I) diagnosis (p = 0.030) were associated with a worse long-term outcome. Electrode placement and medication resistance prior to ECT had no effect on relapse. Adjusting for covariates, fewer patients treated with lithium relapsed in the overall group (p = 0.008) and in the unipolar depression subgroup (p = 0.027). CONCLUSION: Long-term outcome following high-dose right unilateral ECT does not differ from bitemporal ECT. Prognosis is particularly favourable in older adults, psychotic depression and patients maintained on lithium.

Autobiographical Memory Specificity in Major Depression Treated With Electroconvulsive Therapy.

OBJECTIVE: Autobiographical memory in major depression is characterized by reduced specificity, which reflects the tendency to summarize categories of events rather than recall specific instances of events situated in a time and place. This widely studied cognitive marker for depression has not been extensively examined in patients treated with electroconvulsive therapy (ECT). METHODS: We conducted a retrospective chart review of a naturalistic cohort of patients receiving a course of brief-pulse predominantly bitemporal ECT for a major depressive episode. Patients completed the recent life section of the Kopelman Autobiographical Memory Interview (AMI) at pre-ECT baseline, end of treatment course, and 3-month follow-up as part of routine clinical practice. Mood was assessed using the 24-item Hamilton Rating Scale for Depression. RESULTS: We identified 48 patients (mean age, 61.6; female, 62.5%) meeting inclusion criteria. A total of 77.1% of patients responded to the ECT course, 29.7% subsequently relapsed. There were no significant changes over time on either AMI total score or semantic and episodic subscales. However, patients were markedly impaired on episodic autobiographical memory compared with the normative sample at all 3 assessment points, whereas personal semantic memory recall was normal. Specificity of episodic autobiographical memory at baseline did not predict response to ECT or likelihood of relapse. CONCLUSIONS: We found reduced specificity of episodic autobiographical memory in depressed patients before ECT, which persisted at long-term follow-up despite significant improvement in mood. The finding of no detectable retrograde amnesia likely reflects lack of sensitivity of the recent life section of the AMI to detect ECT-induced changes.

Bitemporal Versus High-Dose Unilateral Twice-Weekly Electroconvulsive Therapy for Depression (EFFECT-Dep): A Pragmatic, Randomized, Non-Inferiority Trial.

OBJECTIVE: ECT is the most effective treatment for severe depression. Previous efficacy studies, using thrice-weekly brief-pulse ECT, reported that high-dose (6× seizure threshold) right unilateral ECT is similar to bitemporal ECT but may have fewer cognitive side effects. The authors aimed to assess the effectiveness and cognitive side effects of twice-weekly moderate-dose (1.5× seizure threshold) bitemporal ECT with high-dose unilateral ECT in real-world practice. METHOD: This was a pragmatic, patient- and rater-blinded, noninferiority trial of patients with major depression (N=138; 63% female; age=56.7 years [SD=14.8]) in a national ECT service with a 6-month follow-up. Participants were independently randomly assigned to bitemporal or high-dose unilateral ECT. The primary outcome was change in the 24-item Hamilton Depression Rating Scale (HAM-D) score after the ECT course; the prespecified noninferiority margin was 4.0 points. Secondary outcomes included response and remission rates, relapse status after 6 months, and cognition. RESULTS: Of the eligible patients, 69 were assigned to bitemporal ECT and 69 to unilateral ECT. High-dose unilateral ECT was noninferior to bitemporal ECT regarding the 24-item HAM-D scores after the ECT course (mean difference=1.08 points in favor of unilateral ECT [95% CI=-1.67 to 3.84]). There were no significant differences for response and remission or 6-month relapse status. Recovery of orientation was quicker following unilateral ECT (median=19.1 minutes versus 26.4 minutes). Bitemporal ECT was associated with a lower percent recall of autobiographical information (odds ratio=0.66) that persisted for 6 months. CONCLUSIONS: Twice-weekly high-dose unilateral ECT is not inferior to bitemporal ECT for depression and may be preferable because of its better cognitive side-effect profile.

Relapse following successful electroconvulsive therapy for major depression: a meta-analysis.

High rates of early relapse following electroconvulsive therapy (ECT) are typically reported in the literature. Current treatment guidelines offer little information to clinicians on the optimal nature of maintenance therapy following ECT. The aim of this study was to provide a systematic overview of the existing evidence regarding post-ECT relapse. A keyword search of electronic databases was performed for studies appearing in the peer-reviewed literature before January 2013 reporting on relapse rates in responders to an acute course of ECT administered for a major depressive episode. Meta-analyses were performed where appropriate. Thirty-two studies with up to 2 years' duration of follow-up were included. In modern era studies of continuation pharmacotherapy, 51.1% (95% CI=44.7-57.4%) of patients relapsed by 12 months following successful initial treatment with ECT, with the majority (37.7%, 95% CI=30.7-45.2%) relapsing within the first 6 months. The 6-month relapse rate was similar in patients treated with continuation ECT (37.2%, 95% CI=23.4-53.5%). In randomized controlled trials, antidepressant medication halved the risk of relapse compared with placebo in the first 6 months (risk ratio=0.49, 95% CI=0.39-0.62, p<0.0001, number needed to treat=3.3). Despite continuation therapy, the risk of relapse within the first year following ECT is substantial, with the period of greatest risk being the first 6 months. The largest evidence base for efficacy in post-ECT relapse prevention exists for tricyclic antidepressants. Published evidence is limited or non-existent for commonly used newer antidepressants or popular augmentation strategies. Maintenance of well-being following successful ECT needs to be improved.