Pre-treatment predictors of cognitive side-effects after treatment with electroconvulsive therapy in patients with depression: A multicenter study.

BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective treatment for major depressive episodes (MDE). However, ECT-induced cognitive side-effects remain a concern. Identification of pre-treatment predictors that contribute to these side-effects remain unclear. We examined cognitive performance and individual cognitive profiles over time (up to six months) following ECT and investigated possible pre-treatment clinical and demographic predictors of cognitive decline shortly after ECT. METHODS: 634 patients with MDE from five sites were included with recruitment periods between 2001 and 2020. Linear mixed models were used to examine how cognitive performance, assessed with an extensive neuropsychological test battery, evolved over time following ECT. Next, possible pre-treatment predictors of cognitive side-effects directly after ECT were examined using linear regression. RESULTS: Directly after ECT, only verbal fluency (animal and letter; p < 0.0001; Cohen's d: -0.25 and -0.29 respectively) and verbal recall (p < 0.0001; Cohen's d: -0.26) significantly declined. However, during three and six months of follow-up, cognitive performance across all domains significantly improved, even outperforming baseline levels. No other pre-treatment factor than a younger age predicted a larger deterioration in cognitive performance shortly after ECT. LIMITATIONS: There was a substantial amount of missing data especially at 6 months follow-up. CONCLUSIONS: Our findings show that verbal fluency and memory retention are temporarily affected immediately after ECT. Younger patients may be more susceptible to experiencing these acute cognitive side-effects, which seems to be mostly due to a more intact cognitive functioning prior to ECT. These findings could contribute to decision-making regarding treatment selection, psychoeducation, and guidance during an ECT course.

A Multicenter Retrospective Chart Review on the Effectiveness and Tolerability of Electroconvulsive Therapy in Adolescents and Young Adults With Major Depressive Disorder or Bipolar Depression.

BACKGROUND: Major depressive disorder and bipolar depression in adolescents and young adults are prevalent and major contributors to the global burden of disease, whereas effective interventions are limited. Available evidence is insufficient to assess effectiveness and tolerability of electroconvulsive therapy in depressed adolescents and young adults. METHODS: A retrospective chart review was conducted in patients with major depressive disorder or bipolar depression who underwent electroconvulsive therapy from 2001 to 2021 in 12 centers in the Netherlands. Patients were classified as young (15-25 years) and older adults (26-80 years). Primary outcome was effectiveness, expressed as response (≥50% reduction in rating scale score compared with baseline) and remission. Rating scale scores were cross-sectionally assessed at baseline and at the end of the index course. Outcomes of remitters were included in responders. Secondary outcome was occurrence of subjective cognitive impairment and adverse events. Long-term outcomes were not available. RESULTS: In the young (n = 57) and older adult (n = 41) group, 40.4% and 56.1% (P = 0.153) of patients achieved response and 28.1% and 39.0% (P = 0.281) remission, respectively. Subjective cognitive impairment (80.5% vs 56.3%; P = 0.001) and transient cardiac arrhythmia (14.6% vs 2.8%; P = 0.020) were reported significantly more frequently in the older adult group. CONCLUSIONS: Despite significantly more comorbidity of personality disorders, autism spectrum disorders, and anxiety disorders, effectiveness in the young was similar to the older adults. Tolerability was even superior in the young, despite significantly more bilateral treatment. Electroconvulsive therapy could be considered a viable treatment option in depressed adolescents and young adults.

Rivastigmine for ECT-induced cognitive adverse effects in late life depression (RECALL study): A multicenter, randomized, double blind, placebo-controlled, cross-over trial in patients with depression aged 55 years or older: Rationale, objectives and methods.

Background: Cognitive side-effects are an important reason for the limited use of electroconvulsive therapy (ECT). Cognitive side-effects are heterogeneous and occur frequently in older persons. To date, insight into these side-effects is hampered due to inconsistencies in study designs and small sample sizes. Among all cognitive side-effects, confusion and delirious states are especially troublesome for patients, relatives and clinicians. In particular inter-ictal delirium-like states are worrisome, since they may lead to premature treatment discontinuation. Besides a need for further insight into determinants of cognitive side-effects of ECT, there is a great need for treatment options. Methods and design: The Rivastigmine for ECT-induced Cognitive Adverse effects in Late Life depression (RECALL) study combines a multicenter, prospective cohort study on older patients with depression, treated with ECT, with an embedded randomized, placebo-controlled cross-over trial to examine the effect of rivastigmine on inter-ictal delirium. Patients are recruited in four centers across the Netherlands and Belgium. We aim to include 150 patients into the cohort study, in order to be able to subsequently include 30 patients into the trial. Patients are included in the trial when inter-ictal delirium, assessed by the Confusion Assessment method (CAM), or a drop in Mini Mental State Examination (MMSE) score of ≥4 during ECT, develops. In the cohort study, comprehensive measurements of ECT-related cognitive side-effects-and their putative determinants-are done at baseline and during the ECT-course. The primary outcome of the clinical trial is the effectiveness of rivastigmine on inter-ictal delirium-severity, assessed with a change in the Delirium Rating Scale-Revised-98. Secondary outcomes of the clinical trial are several ECT-characteristics and side-effects of rivastigmine. Discussion: This study is the first clinical trial with a focus on ECT-induced, inter-ictal delirium. The cohort provides the basis for recruitment of patients for the cross-over trial and additionally provides an excellent opportunity to unravel cognitive side-effects of ECT and identify putative determinants. This paper describes the rationale and study protocol. Clinical trial registration: EudraCT 2014-003385-24.

Is ketamine an appropriate alternative to ECT for patients with treatment resistant depression? A systematic review.

OBJECTIVE: Ketamine has repeatedly shown to have rapid and robust antidepressant effects in patients with treatment resistant depression (TRD). An important question is whether ketamine is as effective and safe as the current gold standard electroconvulsive therapy (ECT). METHODS: The literature was searched for trials comparing ketamine treatment with ECT for depression in the Pubmed/MEDLINE database and Cochrane Trials Library. RESULTS: A total of 137 manuscripts were identified, 6 articles were included in this review. Overall quality of the included studies was diverse with relevant risk of bias for some of the studies. Results suggest that ketamine treatment might give faster but perhaps less durable antidepressant effects. Side effects differed from ECT, in particular less cognitive impairment was apparent in ketamine treatment. LIMITATIONS: The included studies have limited sample sizes, use different treatment protocols and in most trials, longer term follow up is lacking. Furthermore, allocation bias appears likely in the non-randomized trials. CONCLUSIONS: Current available literature does not yet provide convincing evidence to consider ketamine as an equally effective treatment alternative to ECT in patients with TRD. There are indications for a more favourable short term cognitive side effect profile after ketamine treatment. Methodologically well-designed studies with larger sample sizes and longer follow up duration are warranted.

Psychotic late-life depression less likely to relapse after electroconvulsive therapy.

BACKGROUND: A substantial number of patients with late-life depression (LLD) that remitted after ECT experience relapse. Identifying risk factors for relapse may guide clinical management to devote attention to those at increased risk. Therefore the current study aims to evaluate which baseline clinical characteristics are related to relapse within six months after successful ECT in patients with severe LLD. METHODS: 110 patients with LLD from the prospective naturalistic follow-up Mood Disorders in Elderly treated with Electro-Convulsive Therapy (MODECT) study were included. A total of 73 patients (66.4%) remitted after ECT, six patients had missing information on relapse, rendering to a total sample size of 67 patients. Relapse within six months after ECT was defined as a Montgomery Åsberg Depression Scale (MADRS)-score > 15, readmission or restart of ECT. Logistic regression analyses were conducted to examine the association between baseline clinical characteristics and relapse. RESULTS: A total of 22 patients (32.8%) experienced a relapse. Patients with psychotic depression were less likely to relapse (odds ratio = 0.32, p = .047), corrected for prior admissions; 76.9% of patients with psychotic depression remained remitted. LIMITATIONS: Due to its naturalistic design, no firm conclusions can be drawn on the effect of post-ECT treatment. CONCLUSIONS: Patients with psychotic depression had a lower risk to experience relapse after successful ECT. This result strengthens the hypothesis that psychotic depression might be a specific depression subtype with a favorable ECT outcome up to six months after ECT.

Psychotic depressive subtype and white mater hyperintensities do not predict cognitive side effects in ECT: A systematic review of pretreatment predictors.

BACKGROUND: Most studies regarding cognitive side-effects following ECT for treating depression report transient forms of cognitive disturbances. However, a growing number of studies also report considerable differences among individual patients. OBJECTIVE: The aim of this systematic review was to identify pretreatment patient characteristics for predicting the risk of developing cognitive side-effects following ECT. METHODS: Online databases PubMed/Medline, Embase, and PsycINFO were searched for articles published from 2002 through May 2019, using the following relevant search terms: #cognitive deficits AND #Electro Convulsive Therapy. Inclusion and exclusion criteria were applied for full-text inclusion. PRISMA guidelines were used. RESULTS: Our initial search yielded 2155 publications; 16 studies were included. A total of 16 possible predictive factors were identified. Two factors, psychotic features and white matter hyperintensities, were conclusively found to not predict cognitive side-effects following ECT; the remaining 14 factors were inconclusive. CONCLUSIONS: There is robust evidence that psychotic features and white matter hyperintensities are not predictive of cognitive side-effects following ECT. None of the other 14 factors examined were predictive, however these levels of evidence were weak and therefore inconclusive. Additional studies focusing primarily on pretreatment patient characteristics for predicting cognitive side-effects following ECT are needed, including demographic, clinical, physiological, neurobiological, and genetic factors. Finally, we provide suggestions for future research.

Chronotherapy Network Netherlands (CNN).

Information is provided about the Chronotherapy Network Netherlands (CNN).

Electroconvulsive Therapy for Agitation and Aggression in Dementia: A Systematic Review.

OBJECTIVES: Many patients with dementia develop agitation or aggression in the course of their disease. In some severe cases, behavioral, environmental, and pharmacological interventions are not sufficient to alleviate these potentially life-threatening symptoms. It has been suggested that in those cases, electroconvulsive therapy (ECT) could be an option. This review summarizes the scientific literature on ECT for agitation and aggression in dementia. METHODS: We performed a systematic review in accordance with PRISMA guidelines. A search was conducted in Ovid MEDLINE, EMBASE, and PsycINFO. Two reviewers extracted the following data from the retrieved articles: number of patients and their age, gender, diagnoses, types of problem behavior, treatments tried before ECT, specifications of the ECT treatment, use of rating scales, treatment results, follow-up data, and adverse effects. RESULTS: The initial search yielded 264 articles, 17 of which fulfilled the inclusion criteria. Of these studies, one was a prospective cohort study, one was a case-control study, and the others were retrospective chart reviews, case series, or case reports. Clinically significant improvement was observed in the majority (88%) of the 122 patients described, often early in the treatment course. Adverse effects were most commonly mild, transient, or not reported. CONCLUSIONS: The reviewed articles suggest that ECT could be an effective treatment for severe and treatment-refractory agitation and aggression in dementia, with few adverse consequences. Nevertheless, because of the substantial risk of selection bias, the designs of the studies reviewed, and their small number, further prospective studies are needed to substantiate these preliminary positive results.

Vascular risk factors in older patients with depression: outcome of electroconvulsive therapy versus medication.

OBJECTIVE: Research suggests that in depression, vascular burden predicts a lower efficacy for medication (MED) and a more favourable outcome for electroconvulsive therapy (ECT). Therefore, we investigated the influence of the following vascular risk factors (VRF): hypercholesterolemia, hypertension, smoking, diabetes mellitus, cardiovascular disease, and cerebral vascular accident/transient ischemic attack, on remission from major depression after ECT versus MED. METHODS: The study sample consisted of 81 inpatients with a DSM-IV unipolar major depression diagnosis (mean age 72.2 years, SD = 7.6, mean Montgomery-Åsberg Depression Rating Scale score 32.9, SD = 6.2) participating in a randomized controlled trial comparing nortriptyline versus venlafaxine and 43 inpatients (mean age 73.7 years, SD = 7.5, mean Montgomery-Åsberg Depression Rating Scale score 30.6, SD = 7.1) from an randomized controlled trial comparing brief pulse versus ultrabrief pulse ECT. The presence of VRF was established from the medical records. The remission rate of patients with VRF was compared with those of patients without VRF. RESULTS: The remission rate was 58% (19/33) in the ECT group with ≥1 VRF and 32% (23/73) in the MED group with ≥1 VRF (χ2  = 6.456, p = 0.011). Comparing patients with no VRF versus ≥1 VRF, the remission rate decreased from 80 to 58% (χ2  = 1.652, p = 0.276) in ECT patients and from 38 to 32% (χ2  = 0.119, p = 0.707) in MED patients. Applying different cut-offs for the number of VRFs yielded the same trends. Logistic regression revealed no interaction between VRF and treatment condition. CONCLUSION: The superior efficacy of ECT over pharmacotherapy in major depression in older age was independent of the presence of VRF. Copyright © 2017 John Wiley & Sons, Ltd.

Early Complete Remitters After Electroconvulsive Therapy: Profile and Prognosis.

OBJECTIVE: To investigate the prevalence, characteristics, and prognosis of depressive patients who show early complete remission after right unilateral (ultra)brief pulse electroconvulsive therapy (ECT). METHODS: Early complete remitters (ECRs) were those patients who were rated 1 on the Clinical Global Impression Scale (maximum score, 7) within 4 ECT sessions and achieved remission (Montgomery Åsberg Depression Rating Scale score, <10). The ECRs were compared with late complete remitters (LCRs), which fulfilled the same criteria after 9 to 12 ECT sessions and with the nonremitters/nonresponders (NRs). RESULTS: Of the 87 patients who completed the index treatment phase, 50 (57.5%) achieved remission. Of these remitters, 12 (14%) were ECRs and 9 (10%) were LCRs. The ECRs were characterized by a higher mean age (71.0 vs 53.9 years; P = 0.008), a shorter current depressive episode (mean, 5.8 vs 15.4 months; P = 0.042), and more psychotic features (75% vs 22%; P = 0.030) and were treated more often with brief pulse ECT (P = 0.030) compared with the LCRs. Although not significant, cognitive performances of ECRs were lower than that of LCRs at baseline with a large effect size: Autobiographical Memory Interview (P = 0.099; d = 0.83), Amsterdam Media Questionnaire (P = 0.114; d = 0.84), and Letter fluency (P = 0.071; d = 0.95). The ECR group had a lower relapse rate during 6 months' follow-up: 10% (1 of 10) versus 62.5% (5 of 8) (P = 0.043). No significant differences in demographic and clinical characteristics were found between LCRs (n = 9) and NRs (n = 27). CONCLUSIONS: Older patients with a psychotic depression and a profile of cognitive slowing have a high chance of achieving complete remission within 4 ECT sessions, with a favorable 6-month prognosis.

Relapse and long-term cognitive performance after brief pulse or ultrabrief pulse right unilateral electroconvulsive therapy: A multicenter naturalistic follow up.

BACKGROUND: Superior cognitive functioning for electroconvulsive therapy (ECT) with right unilateral (RUL) ultrabrief pulse (UBP) stimulation compared to RUL brief pulse (BP) stimulation is not clearly established and long-term data is needed. METHODS: We conducted a prospective naturalistic follow-up of 87 inpatients from three tertiary psychiatric hospitals. Before these patients entered the follow up phase, they had participated in a RCT comparing twice weekly RUL BP (1.0 ms) with RUL UBP (0.3-0.4 ms) ECT eight times seizure threshold until remission (MADRS < 10), for a maximum of six weeks. Three and six months after the index ECT patients were monitored for relapse and cognitive performance (retrograde amnesia, semantic memory and lexical memory). We compared relapse rate and cognitive performance between RUL BP and RUL UBP stimulation. RESULTS: Of the 50 patients who remitted after index ECT 44 (24 BP; 20 UBP) were monitored for follow up. Relapse occurred in 25% of the BP group and in 25% of the UBP group (χ(2) = 0.00, p = 1.0) at three-month follow-up; whereas 43.5% of the BP group and 35% of the UBP group relapsed (χ(2) = 0.322, p = 0.57) at six months follow-up. Cognitive assessments (17 BP; 16 UBP) showed no significant differences between BP and UBP groups, except for an advantage for the BP group in the autobiographical incident questions at three months follow-up only (p = 0.04; d = 0.77). LIMITATIONS: This study may be limited since relapse in a naturalistic follow-up can be influenced by medication and other unknown factors, like social support, medical comorbidity, and psychotherapy. The small numbers of our subgroups hamper statistical significance. CONCLUSIONS: Patients that achieved remission after RUL BP or RUL UBP ECT showed similar relapse rates after three and six months. There was no cognitive advantage of UBP over BP ECT in follow up. CLINICAL TRIALS REGISTRATION: Netherlands trial register www.trialregister.nl registration number NTR1304.

Speed of remission in elderly patients with depression: electroconvulsive therapy v. medication.

BACKGROUND: Severe depression can be a life-threatening disorder, especially in elderly patients. A fast-acting treatment is crucial for this group. Electroconvulsive therapy (ECT) may work faster than medication. AIMS: To compare the speed of remission using ECT v. medication in elderly in-patients. METHOD: The speed of remission in in-patients with a DSM-IV diagnosis of major depression (baseline MADRS score ≥20) was compared between 47 participants (mean age 74.0 years, s.d. = 7.4) from an ECT randomised controlled trial (RCT) and 81 participants (mean age 72.2 years, s.d. = 7.6) from a medication RCT (nortriptyline v. venlafaxine). RESULTS: Mean time to remission was 3.1 weeks (s.d. = 1.1) for the ECT group and 4.0 weeks (s.d. = 1.0) for the medication group; the adjusted hazard ratio for remission within 5 weeks (ECT v. medication) was 3.4 (95% CI 1.9-6.2). CONCLUSIONS: Considering the substantially higher speed of remission, ECT deserves a more prominent position in the treatment of elderly patients with severe depression.

Older age is associated with rapid remission of depression after electroconvulsive therapy: a latent class growth analysis.

OBJECTIVES: This study aims to empirically identify latent course trajectories of depressive symptoms during electroconvulsive therapy (ECT) within a cohort of patients suffering from a depressive disorder and to examine putative predictors of course. METHODS: Using a prospective cohort multicenter collaborative ECT design, 120 patients fulfilling the Mini International Neuropsychiatric Interview criteria for major depressive disorder and referred for ECT were selected. Ratings of the 17-item Hamilton Rating Scale for Depression (HRSD) were obtained weekly during the course of ECT. Latent class growth analysis was used to identify trajectories of course during 6-week follow-up, based on weekly total HRSD scores. Characteristics of the identified classes were examined, and putative predictors for class membership were tested. RESULTS: Data-driven techniques identified distinct course trajectories during 6-week follow-up ECT treatment, consisting of "rapid remission," "moderate response," and "nonremitting" course trajectories. Remission rates were as high as 80.1% in the rapid remission class. Older age was associated with rapid remission, even after adjustment for putative confounders. CONCLUSION: Our results strongly confirm the favorable outcome of ECT among elderly depressed inpatients.

Short- and long-term neurocognitive functioning after electroconvulsive therapy in depressed elderly: a prospective naturalistic study.

BACKGROUND: It is generally assumed that the elderly patients are more vulnerable to cognitive side effects after electroconvulsive therapy (ECT) than younger depressed patients. The current study aims to evaluate the nature and extent of changes across multiple domains of neurocognitive functioning in a group of elderly depressed patients after ECT. METHODS: In this prospective naturalistic study, we included 42 depressed patients aged ≥55 years. Global cognitive function, memory, and executive function were assessed before ECT treatment and within one week (short-term post-ECT) and six months after ECT (long-term post-ECT). Associations between cognitive functioning and electrode placement, total number of treatment sessions, age, and the severity of depression at the time of cognitive measurement were studied. RESULTS: Our data offered no evidence of decline for any of the neurocognitive tests after ECT, given its power to detect the difference. Post-ECT improvement of neurocognitive functioning was statistically significant for the Mini-Mental State Examination, Visual Association Test, 10 Words Verbal Learning Test, and Expanded Mental Control Test. Effect sizes were medium to large. After six months, compared with post-ECT performance, statistically significant improvement was found only for the Trail Making Test-A and the Letter Fluency Test with small to medium effect sizes. CONCLUSIONS: In our severely depressed elderly patients, neurocognitive performance improved or did not change after ECT. Patients with poor cognitive function were not able to participate in neuropsychological assessment before ECT started. Consequently these results may not apply to patients with more severe cognitive impairment prior to the start of ECT.

Efficacy and cognitive side effects after brief pulse and ultrabrief pulse right unilateral electroconvulsive therapy for major depression: a randomized, double-blind, controlled study.

OBJECTIVE: To compare the efficacy and cognitive side effects of high-dose unilateral brief pulse electroconvulsive therapy (ECT) with those of high-dose unilateral ultrabrief pulse ECT in the treatment of major depression. METHOD: From April 2007 until March 2011, we conducted a prospective, double-blind, randomized multicenter trial in 3 tertiary psychiatric hospitals. All patients with a depressive disorder according to DSM-IV criteria were eligible. Depression severity was assessed with the Montgomery-Asberg Depression Rating Scale; primary efficacy outcomes were response, defined as a score decrease ≥ 60% from baseline, and remission, defined as a score < 10 at 2 consecutive weekly assessments. Total scores on the Autobiographical Memory Interview and Amsterdam Media Questionnaire were the primary outcome measures for retrograde amnesia. Other cognitive domains included category fluency (semantic memory) and letter fluency (lexical memory). Patients received twice-weekly unilateral brief pulse (1.0 millisecond) or ultrabrief pulse (0.3-0.4 millisecond) ECT 8 times seizure threshold until remission, for a maximum of 6 weeks. RESULTS: Of the 116 patients, 75% (n = 87) completed the study. Among completers, 68.4% (26/58) of those in the brief pulse group achieved remission versus 49.0% (24/49) of those in the ultrabrief pulse group (P = .019), and the brief pulse group needed fewer treatment sessions to achieve remission: mean (SD) of 7.1 (2.6) versus 9.2 (2.3) sessions (P = .008). No significant group differences were found in the evaluation of the cognitive assessments. CONCLUSIONS: The efficacy and speed of remission seen with high-dose brief pulse right unilateral ECT twice weekly were superior to those seen with high-dose ultrabrief pulse right unilateral ECT, with equal cognitive side effects as defined by retrograde amnesia, semantic memory, and lexical memory. TRIAL REGISTRATION: Netherlands National Trial Register number: NTR1304.