Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. Methods: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R 2) at the optimal p-value threshold is reported. Results: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R 2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R 2 = 8.18%, p = .0013), Belgium (R 2 = 6.83%, p = .016), and the Netherlands (R 2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R 2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R 2 = 4.42%, p = .0024) and unipolar MDE only (R 2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold. Conclusions: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry

ECT-Related Anxiety: A Systematic Review

BACKGROUND: A significant proportion of electroconvulsive therapy (ECT)-treated patients experience anxiety anticipating the treatment, often to such an extent that they refuse or discontinue a much-needed treatment. Despite its great impact on treatment adherence, anxiety in patients receiving ECT is underexposed in the scientific literature. OBJECTIVES: We aimed to review the prevalence and specific subjects of ECT-related anxiety and therapeutic interventions to reduce it. METHODS: We performed a computerized search (EMBASE, MEDLINE, and PsycINFO) for articles meeting the following inclusion criteria: (1) qualitative (interview) studies, quantitative (questionnaire) studies, or experimental (interventional) studies that (2) report on anxiety that is related to a planned, ongoing, or past ECT treatment. RESULTS: Of 1160 search results, 31 articles were included. Electroconvulsive therapy-related anxiety is estimated to be present in 14% to 75% of patients and is most often linked to worries about memory impairment or brain damage. Only a few interventions (chlorpromazine, meprobamate, propofol, a talking-through technique, an information leaflet, and animal-assisted therapy) have been proposed to reduce patients' ECT-related anxiety. CONCLUSIONS: Electroconvulsive therapy-related anxiety is a highly prevalent phenomenon, and the literature provides little guidance for its clinical management. Most studies are of a low methodological quality and suffer from significant limitations, thereby hampering generalized conclusions. Given the clinical importance of ECT-related anxiety, further study on its nature and evolution through the course of treatment and on anxiety-reducing interventions is warranted.status: publishe

The Clinical Practice of Assessing Cognitive Function in Adults Receiving Electroconvulsive Therapy: Whom Are We Missing?

Cognition can be affected by electroconvulsive therapy (ECT). Good clinical practice includes neuropsychological assessment, although this is seldom a part of routine clinical practice. It looks like a substantial part of patients fail to complete cognitive assessments. This constitutes a problem in the generalizability of published clinical research on cognitive side effects. Most studies of ECT-related cognitive adverse effects do not discuss this important issue of so-called cognitive test nonparticipants. Recent findings suggest that cognitive test nonparticipants are more severely ill, and probably more vulnerable to cognitive side effects.status: publishe

Cognitive functioning, sleep quality, and work performance in non-clinical burnout: The role of working memory

We investigated the relationship between cognitive functioning, work performance, and sleep in non-clinical burnout. In a working population, an online survey was conducted with additional online neuropsychological tests of varying complexity, measuring attention and different components of working memory, of which the coordinating subcomponent the 'Central Executive' is thought to be the most vulnerable to stress. Results indicate that nonclinical burnout is associated with more - though not severe - sleep problems, more depressive complaints, impaired work performance, and with both subjective and objective cognitive impairments. Compared with healthy respondents (N = 107), people with non-clinical burnout (N = 17) had a significantly poorer performance on the tests of the visuospatial sketchpad and the Central Executive of the working memory. Our study also indicates that more complex tests may be more sensitive in detecting cognitive dysfunction in non-clinical burnout. Furthermore, a relationship was found between dual-task performance and work performance. Regarding to sleep quality, in our sample of people with non-clinical burnout, there were no severe sleep problems. In the entire sample, however, insomnia was significantly related to subjective, but not objective, cognitive functioning, and also not to work performance

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Neurocognitive functioning after electroconvulsive therapy in late-life depression: A 4-year prospective study

Objective: Despite the proven efficacy and safety of ECT, there is still concern about the possible cognitive side effects of ECT in older patients. In this study, we aimed to characterize the long-term cognitive effects of ECT in patients with late-life depression (LLD) from before the start until 4 years after the index ECT course. Methods: Fourty one patients aged 55 years and older with a unipolar depression, referred for ECT, were included. The neuropsychological test battery was assessed prior to ECT, 6 months, 1 year, 2 years, 3 years, and 4 years after the last ECT session. Results: We did not find any statistically significant cognitive changes from before the start to 4 years after ending the ECT course. Although we could not detect cognitive changes at group level, we found clinically important differences on an individual level. Conclusion: Cognitive performance in patients with LLD runs a stable course from before the start of ECT until 4 years after the index course. At an individual level, however, both cognitive decline and improvement can be witnessed. Older patients can tolerate ECT and most of them will not experience long-term cognitive side effects

MMSE Changes During and After ECT in Late-Life Depression: A Prospective Study

Objective: There is ongoing concern about the impact of electroconvulsive therapy (ECT) on cognition in patients with late-life depression (LLD), especially in patients for whom pretreatment Mini-Mental State Exam (MMSE) scores are low. Our aim was to examine the evolution of cognitive effects of ECT, using the MMSE in a large group of patients with LLD. Methods: One hundred nine patients aged 55 years and older with unipolar depression, referred for ECT, were included in our study. The MMSE was assessed before, during, immediately after, and 6 months after ECT. Results: MMSE scores improved significantly during the course of ECT and remained stable during the 6-month period after ending ECT for the total group. In the group of patients with a low MMSE score (<24) at baseline, the MMSE score improved significantly during ECT, whereas in the group of patients with a normal MMSE score (≥24) at baseline, the score did not change significantly during ECT. In both groups, MMSE scores still increased slightly after ECT was discontinued. Conclusion: ECT does not cause deleterious cognitive effects, as measured with the MMSE, during and for 6 months after the ECT course in patients with LLD. In the event of a baseline cognitive impairment, MMSE scores tend to improve significantly during and for 6 months after the ECT course. The presence of pretreatment cognitive impairment should not lead clinicians to withhold ECT in older patients with severe depression

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

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

Pharmacological interventions to diminish cognitive side effects of electroconvulsive therapy: A systematic review and meta-analysis

Objective: The authors conducted a systematic review and meta-analysis of pharmacological interventions to diminish cognitive side effects of ECT. Methods: Electronic databases of Pubmed, PsycInfo, Embase and Scopus were searched from inception through 1 April, 2021, using terms for ECT (e.g. electroconvulsive therapy), cognitive outcome (e.g. cogni*) and pharmacological intervention (e.g. calcium channel blocker and general terms, like protein). Original studies with humans receiving ECT were included, which applied pharmacological interventions in comparison with placebo or no additive intervention to diminish cognitive side effects. Data quality was assessed using Risk of Bias and GRADE. Random-effects models were used. PROSPERO registration number was CRD42021212773. Results: Qualitative synthesis (systematic review) showed 52 studies reporting sixteen pharmacological intervention-types. Quantitative synthesis (meta-analysis) included 26 studies (1387 patients) describing twelve pharmacological intervention-types. Low-quality evidence of efficacy was established for memantine (large effect size) and liothyronine (medium effect size). Very low-quality evidence shows effect of acetylcholine inhibitors, piracetam and melatonin in some cognitive domains. Evidence of no efficacy was revealed for ketamine (very low-quality), herbal preparations with anti-inflammatory properties (very low to low-quality) and opioid receptor agonists (low-quality). Conclusion: Memantine and liothyronine are promising for further research and future application. Quality of evidence was low because of differences in ECT techniques, study populations and cognitive measurements. These findings provide a guide for rational choices of potential pharmacological intervention research targets to decrease the burden of cognitive side effects of ECT. Future research should be more uniform in design and attempt to clarify pathophysiological mechanisms of cognitive side effects of ECT