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The effectiveness of electroconvulsive therapy (ECT) for people with bipolar disorder: is there a specific role?
Expert Review of Neurotherapeutics
Abstract
Introduction:
Electroconvulsive therapy (ECT) has been used for over 80 years to treat various neuropsychiatric conditions, including mood and psychotic disorders. Despite its proven efficacy, ECT remains underutilized and underexplored in patients with bipolar disorder (BD).
Areas covered:
This perspective examines the role of ECT in BD, highlighting its effectiveness across depressive, manic, and mixed phases, including those characterized by catatonic or delirious features. Based on these findings, the authors propose a comprehensive transdiagnostic framework to conceptualize ECT-responsive syndromes based on psychomotor, psychotic, and cognitive disturbances. The potential long-term effectiveness of ECT as a mood stabilizer is also suggested, despite the limited amount of literature. Finally, safety issues and alternative options are discussed.
Expert opinion:
The shift in ECT usage, from being a first-line treatment for severe affective episodes to a 'last-resort' option for treatment-resistant depression, may have contributed to increased relapse rates and chronicity. Considering ECT at an early stage, potentially even before any medication trials, is recommended for specific clinical conditions associated with BD and marked by objective psychomotor disturbances, acute psychotic symptoms, and severe cognitive alterations.
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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.
Even though pseudodementia has been historically linked to depression, other psychiatric conditions may cause reversible cognitive alterations. The purpose of this study is to improve our understanding of pseudodementia occurring throughout the entire bipolar spectrum. A systematic review was conducted according to PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched up to March 2023. Fifteen articles on patients with pseudodementia and bipolar disorder (BD), mania, hypomania, or mixed depression have been included. Moreover, seven female patients with mood disorders diagnosed with pseudodementia have been described. According to our research, pseudodementia in patients with BD mostly occurs during a depressive episode. However, pseudodementia has also been observed in the context of manic and mixed states. Psychomotor and psychotic symptoms were commonly associated. The most typical cogni-tive impairments were disorientation, inattention, and short-term memory deficits. Alterations in neuroimaging were frequently observed. Electroconvulsive therapy and lithium, either alone or in combination with antipsychotics, resulted in the most widely used therapies. Cognitive decline may occur in a substantial proportion of patients. Since pseudodementia can manifest along the entire mood spectrum, it should be taken into consideration as a possible diagnosis in BD patients showing cognitive deficits during manic, mixed, and depressive states.
Background:
Although major depressive disorder (MDD) and bipolar depression can present with similar symptoms, biological differences exist. One difference is the possible variance in adverse effects associated with treatment. This study examined the association of cognitive impairment and delirium in patients treated with electroconvulsive therapy (ECT) plus lithium for MDD or bipolar depression.
Methods:
The Nationwide Inpatient Sample included 210 adults receiving ECT plus lithium. Descriptive statistics and a Chi-square test were used to evaluate the differences between mild cognitive impairment and drug-induced delirium for those with MDD or bipolar depression. We calculated the odds ratio (OR) for drug-induced delirium in inpatients with MDD (compared to inpatients with bipolar depression) using a binomial logistic regression model.
Results:
Mild cognitive impairment was observed in 9.1% of patients with MDD (n = 110), compared to 0 in bipolar depression (n = 100) (P = .002). Drug-induced delirium was more prevalent in MDD (OR 1.19; 95% CI, 1.11 to 1.30).
Conclusions:
ECT plus lithium is associated with less cognitive impairment and drug-induced delirium in bipolar depression compared to MDD. This study may also support biological differences between the 2 types of depression.
Aims
Bipolar disorders are clinically complex, chronic and recurrent disorders. Few treatment options are effective across hypomanic, manic, depressive and mixed states, and as continuation or maintenance treatment after initial symptom remission. The aim of this review was to provide an up-to-date overview of research on the efficacy, tolerability and cognitive effects of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), magnetic seizure therapy (MST), deep brain stimulation (DBS) and vagus nerve stimulation (VNS).
Methods
References included in this review were identified through multiple searches of the Embase, PubMed/MEDLINE and APA PsycINFO electronic databases for articles published from inception until February 2022. Published reviews, meta-analyses, randomised controlled trials and recent studies were prioritised to provide a comprehensive and up-to-date overview of research on brain stimulation in patients with bipolar disorders.
Results
The evidence-base for brain stimulation as an add-on or alternative to pharmacological and psychological treatments in patients with bipolar disorders is limited but rapidly expanding. Brain stimulation treatments represent an opportunity to treat all bipolar disorder states, including cognitive dysfunction during euthymic periods.
Conclusion
While findings to date have been encouraging, larger randomised controlled trials with long-term follow-up are needed to clarify important questions regarding treatment efficacy and tolerability, the frequency of treatment-emergent affective switches and effects on cognitive function.
Importance:
Knowledge of the effectiveness of electroconvulsive therapy (ECT) in the treatment of manic episodes is based on clinical experience, but empirical evidence is scarce. Moreover, prognostic factors associated with response to ECT in patients with mania are poorly understood.
Objective:
To investigate the response to ECT in patients with manic episodes.
Design, setting, and participants:
This nationwide, register-based observational cohort study was conducted using data from patients admitted to psychiatric departments in Sweden that reported data to the Swedish National Quality Registry for ECT (Q-ECT). Patients admitted to any hospital in Sweden and receiving ECT for a manic episode between 2012 and 2019 were considered for inclusion (605 individuals). The outcome, Clinical Global Impression Improvement scale (CGI-I) score, was available in 571 patients. Data from several national registers were combined to determine clinical and sociodemographic factors. Analysis of data occurred from April through September 2021.
Exposures:
Patients treated with ECT for a mania were identified from the Q-ECT.
Main outcomes and measures:
Response to ECT was defined by a CGI-I score of 1 (very much improved) or 2 (much improved). Remission was defined as a Clinical Global Impression Severity scale (CGI-S) score of 1 (reference range or not ill) or 2 (minimally ill) within 1 week after ECT. Univariate and multivariable regression models were used to investigate associations of sociodemographic factors, psychopharmacology, and comorbidities with response.
Results:
Among 571 patients with mania treated with ECT (211 [37.0%] men; median [IQR] age, 46 [31-59] years), 482 patients (84.4%) responded to ECT. Comorbid anxiety and obsessive-compulsive disorder (OCD) were associated with lower odds of response to ECT (adjusted odds ratio [aOR], 0.48; 95% CI, 0.25-0.90 and aOR, 0.17; 95% CI, 0.06-0.56, respectively). Patients who were markedly ill (aOR, 2.93; 95% CI, 1.23-7.00), severely ill (aOR, 2.60; 95% CI, 1.06-6.34), or among the most extremely ill (aOR, 7.94; 95% CI, 2.16-29.21) according to CGI-S score had higher odds of response than those with mild or moderate illness.
Conclusions and relevance:
This study found that ECT was associated with improvement for mania in clinical settings, with especially high response rates in patients with severe illness and those without comorbid anxiety or OCD.
Magnetic seizure therapy (MST) has established efficacy in the treatment of depression and a growing evidence base in the treatment of depression. We conducted the first systematic review and meta-analysis of the efficacy of MST in anti-depressive treatment and its impact on cognitive function (INPLASY registration number: INPLASY202170061). We searched for controlled trials published in English between 1 January 2001 to 31 December 2020 in PubMed, EMBASE, Cochrane Library, Web of Science, and PsycINFO databases. The evaluation process strictly followed the Cochrane bias risk assessment tool into the literature, and Meta-analysis was performed according to the Cochrane System Reviewer’s Manual. Data from a total of 285 patients from 10 studies were retained in the quantitative synthesis. The results showed no significant difference between MST and ECT in the antidepressant effect (SDM −0.13 [−0.78;0.52]). Compared with ECT, MST showed shorter recovery time (MD −5.67 [−9.75; −1.60]) and reorientation time (MD −14.67 [−27.96; −1.41]); and MST showed less cognitive impairment on the immediate recall of words (SDM 0.80 [0.35;1.25]), delayed recall of words (SDM 0.99 [0.01;0.74]), visual-spatial immediate memory (SDM 0.51 [0.20;0.83]), visual-spatial delayed memory (SDM 0.57 [0.11;1.02]), and the verbal fluency (SDM 0.51 [0.20;0.83]). Our evidence-based study is the first meta-analysis on the efficacy of MST in anti-depressive treatment and its effect on cognitive function. It showed that the curative effect of MST in anti-depressive treatment is equivalent to that of ECT. Besides, depressive patients with MST benefit more from cognitive function compared with ECT.
Background and Objectives: Unstable mixed episodes or rapid switching between opposite affective poles within the scope of short cycles was first characterized in 1967 by S. Mentzos as complex polymorphous states with chaotic overlap of manic and depressive symptoms. Well-known examples include antidepressant-induced mania/hypomania and rapid/ultra-rapid/ultradian cycling, when clinicians observe an almost continuous mixed state with a constant change of preponderance of manic or depressive symptoms. Achieving stable remission in these cases is challenging with almost no data on evidence-based treatment. When mood stabilizers are ineffective, electroconvulsive therapy (ECT) has been suggested. Objectives: After reviewing the evidence from available literature, this article presents our own clinical experience of ECT efficacy and tolerability in patients with ultra-rapid cycling bipolar disorder (BD) and unstable mixed states. Materials and Methods: We conducted an open, one-year observational prospective study with a “mirror image” design, including 30 patients with rapid and ultra-rapid cycling BD on long-term mood stabilizer treatment (18 received lithium carbonate, 6 on valproate and 6 on carbamazepine) with limited effectiveness. A bilateral ECT course (5–10 sessions) was prescribed for regaining mood stability. Results: ECT was very effective in 12 patients (40%) with a history of ineffective mood stabilizer treatment who achieved and maintained remission; all of them received lithium except for 1 patient who received carbamazepine and 2 with valproate. Nine patients (30%) showed partial response (one on carbamazepine and two on valproate) and nine patients (30%) had no improvement at all (four on carbamazepine and two on valproate). For the whole sample, the duration of affective episodes was significantly reduced from 36.05 ± 4.32 weeks in the year prior to ECT to 21.74 ± 12.14 weeks in the year post-ECT (p < 0.001). Depressive episodes with mixed and/or catatonic features according to DSM-5 specifiers were associated with a better acute ECT response and/or long-term mood stabilizer treatment outcome after ECT. Conclusions: ECT could be considered as a useful option for getting mood instability under control in rapid and ultra-rapid cycling bipolar patients. Further randomized trials are needed to confirm these results.
Electroconvulsive Therapy (ECT) is an established treatment choice for severe, treatment-resistant depression, yet its mechanisms of action remain elusive. Magnetic resonance imaging (MRI) of the human brain before and after treatment, has been crucial to aid our comprehension of the ECT neurobiological effects. However, to date the majority of MRI studies have been underpowered, used heterogeneous patient samples as well as different methodological approaches, altogether causing mixed results and poor clinical translation. Hence, an association between MRI markers and therapeutic response remains to be established. Recently, the availability of large datasets through a global collaboration has provided the statistical power needed to characterize whole-brain structural and functional brain changes following ECT. In addition, MRI technological developments allow new aspects of brain function and structure to be investigated. Finally, more recent studies have also investigated immediate and long-term effects of ECT, which may aid in the separation of the therapeutically relevant effects from epiphenomena. The goal of the present review is to outline MRI studies (T1, Diffusion-weighted imaging, 1-Hydrogen Magnetic Resonance Spectroscopy) of ECT in depression, to advance our understanding of the ECT neurobiological effects. Based on the reviewed literature, we suggest a model whereby the neurobiological effects can be understood within a framework of disruption, neuroplasticity and rewiring of neural circuits. An improved characterization of the neurobiological effects of ECT may increase our understanding of ECT´s therapeutic effects, ultimately leading to improved patient care.
Psychomotor dysfunction (PMD) is a core element and key contributor to disability in late life depression (LLD), which responds well to electroconvulsive therapy (ECT). The neurobiology of PMD and its response to ECT are not well understood. We hypothesized that PMD in LLD is associated with lower striatal volume, and that striatal volume increase following ECT explains PMD improvement. We analyzed data from a two-center prospective cohort study of 110 LLD subjects (>55 years) receiving ECT. Brain MRI and assessment of mood, cognition, and PMD was performed 1 week before, 1 week after, and 6 months after ECT. Volumetry of the caudate nucleus, putamen, globus pallidus, and nucleus accumbens was derived from automatically segmented brain MRIs using Freesurfer®. Linear multiple regression analyses were used to study associations between basal ganglia volume and PMD. Brain MRI was available for 66 patients 1 week post ECT and in 22 patients also six months post ECT. Baseline PMD was associated with a smaller left caudate nucleus. One week after ECT, PMD improved and volume increases were detected bilaterally in the caudate nucleus and putamen, and in the right nucleus accumbens. Improved PMD after ECT did not relate to the significant volume increases in these structures, but was predicted by a nonsignificant volume change in the right globus pallidus. No volume differences were detected 6 months after ECT, compared to baseline. Although PMD is related to lower striatal volume in LLD, ECT-induced increase of striatal volume does not explain PMD improvement.
Background:
Treatment-resistant bipolar depression can be treated effectively using electroconvulsive therapy, but its use is limited because of stigma and cognitive adverse effects. Magnetic seizure therapy is a new convulsive therapy with promising early evidence of antidepressant effects and minimal cognitive adverse effects. However, there are no clinical trials of the efficacy and safety of magnetic seizure therapy for treatment-resistant bipolar depression.
Methods:
Participants with treatment-resistant bipolar depression were treated with magnetic seizure therapy for up to 24 sessions or until remission. Magnetic seizure therapy was applied over the prefrontal cortex at high (100 Hz; n = 8), medium (50 or 60 Hz; n = 9) or low (25 Hz; n = 3) frequency, or over the vertex at high frequency (n = 6). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression. Participants completed a comprehensive battery of neurocognitive tests.
Results:
Twenty-six participants completed a minimally adequate trial of magnetic seizure therapy (i.e., ≥ 8 sessions), and 20 completed full treatment per protocol. Participants showed a significant reduction in scores on the Hamilton Rating Scale for Depression. Adequate trial completers had a remission rate of 23.1% and a response rate of 38.5%. Per-protocol completers had a remission rate of 30% and a response rate of 50%. Almost all cognitive measures remained stable, except for significantly worsened recall consistency on the autobiographical memory inventory.
Limitations:
The open-label study design and modest sample size did not allow for comparisons between stimulation parameters.
Conclusion:
In treatment-resistant bipolar depression, magnetic seizure therapy produced significant improvements in depression symptoms with minimal effects on cognitive performance. These promising results
warrant further investigation with larger randomized clinical trials comparing magnetic seizure therapy to electroconvulsive therapy.
Clinical trial registration:
NCT01596608; clinicaltrials.gov
Background: Lithium is a helpful adjunct to patients undergoing ECT. However, only case reports and limited data suggest increase risk of delirium. Thus, this continues to be a controversial issue.
Objective: In this study, we examine 1) The association and odds of delirium and cognitive problems with ECT and lithium (ECT+Li) combination compared to ECT alone, 2) If positively associated, would this association vary by both type of mood episode and type of disorder?
Methods: A national sample of 64,728 adult psychiatric inpatients across the US (identified from a total data of about 70 million total discharges annually) was analyzed using linear-by-linear association and logistic regression to assess the odds ratio (OR) for delirium and cognitive impairment for those treated with lithium (N=158), ECT (N=64148), or ECT+ Li (N=422) after adjusting for demographics and psychiatric diagnoses.
Results: The prevalence of delirium was higher in the ECT+Lithium group (5.7%) vs. ECT only (0.6%) or lithium only groups (0%). Patients managed with ECT+Lithium have 11.7-fold higher odds (95%CI 7.55–17.99, P<.001) of delirium compared to ECT alone. In the ECT+Li group, delirium prevalence was 7.8% in unipolar depression, 3.4% in bipolar depressed, 0% in bipolar mania.
Conclusion(s): These results are surprising given the fading concern about delirium association with ECT+lithium combination. The high odds in the combination group warrant clinical caution, use of lower lithium doses (if combinations cannot be avoided), and vigilance regarding early signs of delirium. These results warrant replication in future studies.
Objective:
Electroconvulsive therapy (ECT) is used in patients with severe forms of bipolar depression. ECT is effective but not all patients respond. The aim of this study was to determine prognostic factors for response to ECT in patients hospitalized for bipolar depression.
Methods:
Data were obtained from several national Swedish registers. All patients with bipolar depression treated with ECT in any hospital in Sweden between 2011 and 2016 for whom information about ECT response was available were included (n = 1251). Response was defined as a score on the Clinical Global Impression - Improvement scale of one or two. Univariate and multivariate logistic regression were conducted to investigate associations between socio-demographic and clinical factors and response.
Results:
Response was achieved in 80.2% patients. Older age was associated with higher response rate to ECT. Patients with comorbid obsessive-compulsive disorder or personality disorder, and patients previously treated with lamotrigine had lower response rate.
Conclusion:
ECT for bipolar depression was associated with very high response rates. The strongest prognostic factors were higher age, absence of comorbid obsessive-compulsive disorder or personality disorder, and less prior pharmacologic treatment. This article is protected by copyright. All rights reserved.
Background
Electroconvulsive therapy (ECT) is an effective treatment for all bipolar states. However, ECT remains underutilized, likely stemming from stigma and the risk of neurocognitive impairment. Neuroimaging research has identified state-specific areas of aberrant brain activity that may serve as targets for therapeutic brain stimulation. Electrode placement determines the geometry of the electric field and can be either non-focal (bitemporal) or more focal (right unilateral or bifrontal). Previous research has shown that electrode placement can impact clinical and cognitive outcomes independent of seizure activity. This review critically examines the evidence that focal (unilateral or bifrontal) electrode placements target specific aberrant circuitry in specific bipolar states to optimize clinical outcomes. We hypothesize that optimal target engagement for a bipolar state will be associated with equivalent efficacy relative to bitemporal non-focal stimulation with less neurocognitive impairment.
Methods
We performed a literature search in the PubMed database. Inclusion criteria included prospective, longitudinal investigations during the ECT series with specific electrode placements within a bipolar state from 2000 to 2018.
Results
We identified investigations that met our inclusion criteria with bipolar mania (n = 6), depression (n = 6), mixed (n = 3) and catatonia (n = 1) states. These studies included clinical outcomes and several included cognitive outcomes, which were discussed separately.
Conclusions
While the heterogeneity of the studies makes comparisons difficult, important patterns included the reduced cognitive side effects, faster rate of response, and equivalent efficacy rates of the focal electrode placements (right unilateral and bifrontal) when compared to non-focal (bitemporal) placement. Further avenues for research include more robust cognitive assessments to separate procedure-related and state-related impairment. In addition, future studies could investigate novel electrode configurations with more specific target engagement for different bipolar states.
Importance
Although electroconvulsive therapy (ECT) is considered the most efficacious treatment available for individuals with severe affective disorders, ECT’s availability is limited and declining, suggesting that information about the population-level effects of ECT is needed.
Objective
To examine whether inpatient treatment with ECT is associated with a reduction in 30-day psychiatric readmission risk in a large, multistate sample of inpatients with severe affective disorders.
Design, Setting, and Participants
A quasi-experimental instrumental variables probit model of the association correlation of ECT administration with patient risk of 30-day readmission was estimated using observational, longitudinal data on hospital inpatient discharges from US general hospitals in 9 states. From a population-based sample of 490 252 psychiatric inpatients, a sample was drawn that consisted of 162 691 individuals with a principal diagnosis of major depressive disorder (MDD), bipolar disorder, or schizoaffective disorder. The key instrumental variable used in the analysis was ECT prevalence in the prior calendar year at the treating hospital. To examine whether ECT’s association with readmissions was heterogeneous across population subgroups, analyses included interactions of ECT with age group, sex, race/ethnicity, and diagnosis group. The study was conducted from August 27, 2015, to March 7, 2017.
Main Outcome and Measures
Readmission within 30 days of being discharged.
Results
Overall, 2486 of the 162 691 inpatients (1.5%) underwent ECT during their index admission. Compared with other inpatients, those who received ECT were older (mean [SD], 56.8 [16.5] vs 45.9 [16.5] years; P < .001) and more likely to be female (65.0% vs 54.2%; P < .001) and white non-Hispanic (85.3% vs 62.1%; P < .001), have MDD diagnoses (63.8% vs 32.0%; P < .001) rather than bipolar disorder (29.0% vs 40.0%; P < .001) or schizoaffective disorder (7.1% vs 28.0%; P < .001), have a comorbid medical condition (31.3% vs 26.6%; P < .001), have private (39.4% vs 21.7%; P < .001) or Medicare (49.2% vs 39.4%; P < .001) insurance coverage, and be located in urban small hospitals (31.2% vs 22.3%; P < .001) or nonurban hospitals (9.0% vs 7.6%; P = .02). Administration of ECT was associated with a reduced 30-day readmission risk among psychiatric inpatients with severe affective disorders from an estimated 12.3% among individuals not administered ECT to 6.6% among individuals administered ECT (risk ratio [RR], 0.54; 95% CI, 0.28-0.81). Significantly larger associations with ECT on readmission risk were found for men compared with women (RR, 0.44; 95% CI, 0.20-0.69 vs 0.58; 95% CI, 0.30-0.88) and for individuals with bipolar disorder (RR, 0.42; 95% CI, 0.17-0.69) and schizoaffective disorder (RR, 0.44; 95% CI, 0.11-0.79) compared with those who had MDD (RR, 0.53; 95% CI, 0.26-0.81).
Conclusions and Relevance
Electroconvulsive therapy may be associated with reduced short-term psychiatric inpatient readmissions among psychiatric inpatients with severe affective disorders. This potential population health effect may be overlooked in US hospitals’ current decision making regarding the availability of ECT.
We aimed to review and discuss the evidence-based arguments for the efficacy of electroconvulsive therapy (ECT) in the treatment of catatonia. Randomized controlled trials (RCTs) and observational studies focusing on the response to ECT in catatonia were selected in PubMed, the Cochrane Library, Embase, ClinicalTrials.gov and Current Controlled Trials through October 2016 and qualitatively described. Trials assessing pre-post differences using a catatonia or clinical improvement rating scale were pooled together using a random effect model. Secondary outcomes were adverse effects of anesthesia and seizure. 564 patients from 28 studies were included. RCTs were of low quality and were heterogeneous; therefore, it was not possible to combine their efficacy results. An improvement of catatonic symptoms after ECT treatment was evidenced in ten studies (SMD = −3.14, 95% CI [−3.95; −2.34]). The adverse effects that were reported in seven studies included mental confusion, memory loss, headache, or adverse effects associated with anesthesia. ECT protocols were heterogeneous. The literature consistently describes improvement in catatonic symptoms after ECT. However, the published studies fail to demonstrate efficacy and effectiveness. It is now crucial to design and perform a quality RCT to robustly validate the use of ECT in catatonia.
Prospero registration information: PROSPERO 2016: CRD42016041660
Mixed states represent a frequent presentation of bipolar disorder, associated with higher resistance to psychopharmacology. Limited evidence supports the use of ECT in these patients. We aim to report our experience on treating bipolar mixed states with ECT.
Methods.
Retrospective data were collected from all bipolar patients submitted to acute ECT treatment, between June 2006 and June 2011. Three groups were created in terms of affective polarity of the episode. CGI rating was used to establish clinical remission and demographic and clinical variables were compared among groups. Long-term outcome was assessed through readmission measures, considering the use of continuation or maintenance ECT.
Results.
During the study time frame, a total of 50 ECT course treatments were performed on 41 bipolar patients. All affective episodes, except one mixed state, showed a positive clinical response. Patients with mixed state presentation tended to be younger and have an earlier first hospitalization than depressed patients. No differences were found in terms of ECT sessions performed, length of hospital admission, referral to continuation ECT treatment, number of readmissions, and time until next readmission.
Conclusions.
Our results support the effectiveness of ECT in patients experiencing a mixed affective state.
Background:
The evidence on the mechanisms of action of electroconvulsive therapy (ECT) has grown over the past decades. Recent studies show an ECT-related increase in hippocampal, amygdala and subgenual cortex volume. We examined grey matter volume changes following ECT using voxel-based morphometry (VBM) whole brain analysis in patients with severe late life depression (LLD).
Methods:
Elderly patients with unipolar depression were treated twice weekly with right unilateral ECT until remission on the Montgomery-Åsberg Depression Rating Scale (MADRS) was achieved. Cognition (Mini Mental State Examination) and psychomotor changes (CORE Assessment) were monitored at baseline and 1 week after the last session of ECT. We performed 3 T structural MRI at both time points. We used the VBM8 toolbox in SPM8 to study grey matter volume changes. Paired t tests were used to compare pre- and post-ECT grey matter volume (voxel-level family-wise error threshold p < 0.05) and to assess clinical response.
Results:
Twenty-eight patients (mean age 71.9 ± 7.8 yr, 8 men) participated in our study. Patients received a mean of 11.2 ± 4 sessions of ECT. The remission rate was 78.6%. Cognition, psychomotor agitation and psychomotor retardation improved significantly (p < 0.001). Right-hemispheric grey matter volume was increased in the caudate nucleus, medial temporal lobe (including hippocampus and amygdala), insula and posterior superior temporal regions but did not correlate with MADRS score. Grey matter volume increase in the caudate nucleus region correlated significantly with total CORE Assessment score (r = 0.63; p < 0.001).
Limitations:
Not all participants were medication-free.
Conclusion:
Electroconvulsive therapy in patients with LLD is associated with significant grey matter volume increase, which is most pronounced ipsilateral to the stimulation side.
A low-grade inflammatory response is commonly seen in the peripheral blood of major depressive disorder (MDD) patients, especially those with refractory and chronic disease courses. However, electroconvulsive therapy (ECT), the most drastic intervention reserved for these patients, is closely associated with an enhanced haematogenous as well as neuroinflammatory immune response, as evidenced by both human and animal studies. A related line of experimental evidence further shows that inflammatory stimulation reinforces neurotrophin expression and may even mediate dramatic neurogenic and antidepressant-like effects following exposure to chronic stress. The current review therefore attempts a synthesis of our knowledge on the neurotrophic and immunological aspects of ECT and other electrically based treatments in psychiatry. Perhaps contrary to contemporary views, we conclude that targeted potentiation, rather than suppression, of inflammatory responses may be of therapeutic relevance to chronically depressed patients or a subgroup thereof.
Objectives
Cerebral Small Vessel Disease (CSVD) is a chronic, progressive vascular disorder that confers increased vulnerability to psychiatric syndromes, including late‐life mood disorders. In this study, we investigated the impact of CSVD on electroconvulsive therapy (ECT) outcomes in patients with late‐onset bipolar disorder (BD).
Methods
A sample of 54 non‐demented elderly patients (≥60 years) with late‐onset BD and treatment‐resistant major depression, mixed state, or catatonia who underwent bilateral ECT were included in this naturalistic observational study. A diagnosis of CSVD was established based on brain neuroimaging performed before ECT. All patients were evaluated before and after ECT using the Brief Psychiatric Rating Scale (BPRS), the Hamilton Rating Scale for Depression (HAM‐D), and the Clinical Global Impression scale (CGI).
Results
Of the total sample, 19 patients were diagnosed with CSVD (35.2%). No significant differences were observed at baseline between patients with and without CSVD. Overall, a response was obtained in 66%–68.5% of patients, with remission in 56.2%. No significant differences in ECT outcomes were found between those with and without CSVD, and both groups exhibited substantial improvements in symptom severity following ECT.
Conclusions
The outcome of ECT in late‐onset BD was not influenced by the presence of CSVD. This finding aligns with previous research on unipolar depression. Accordingly, ECT should be considered for elderly patients with late‐onset BD, regardless of the presence of CSVD.
Importance
Bipolar mania is a common disabling illness. Electroconvulsive therapy (ECT) is an effective treatment for patients with severe mania, though it is limited by the risk of cognitive adverse effects. Magnetic seizure therapy (MST) as an alternative treatment to ECT for bipolar mania has not yet been reported.
Objective
To compare the effectiveness and cognitive adverse effects of MST and ECT in bipolar mania.
Design, Setting, and Participants
This randomized clinical trial was conducted at the Shanghai Mental Health Center from July 1, 2017, through April 26, 2021. Forty-eight patients with bipolar mania were recruited and randomly allocated to receive MST or ECT. The data analysis was performed from June 5, 2021, through August 30, 2023.
Interventions
Patients completed 2 or 3 sessions of MST or ECT per week for a total of 8 to 10 sessions. The MST was delivered at 100% device output with a frequency of 75 Hz over the vertex.
Main Outcomes and Measures
The primary outcomes were reduction of total Young Manic Rating Scale (YMRS) score and response rate (more than 50% reduction of the total YMRS score compared with baseline). An intention-to-treat (ITT) analysis and repeated-measures analyses of variance were conducted for the primary outcomes.
Results
Twenty patients in the ECT group (mean [SD] age, 31.6 [8.6] years; 12 male [60.0%]) and 22 patients in the MST group (mean [SD] age, 34.8 [9.8] years; 15 male [68.2%]) were included in the ITT analysis. The response rates were 95.0% (95% CI, 85.4%-100%) in the ECT group and 86.4% (95% CI, 72.1%-100%) in the MST group. The YMRS reduction rate ( z = −0.82; 95% CI, −0.05 to 0.10; P = .41) and response rate (χ ² = 0.18; 95% CI, −0.13 to 0.31; P = .67) were not significantly different between the groups. The time-by-group interaction was significant for the language domain ( F 1,24 = 7.17; P = .01), which was well preserved in patients receiving MST but worsened in patients receiving ECT. No serious adverse effects were reported in either group.
Conclusions and Relevance
These findings suggest that MST is associated with a high response rate and fewer cognitive impairments in bipolar mania and that it might be an alternative therapy for the treatment of bipolar mania.
Trial Registration
ClinicalTrials.gov Identifier: NCT03160664
Background:
Electroconvulsive therapy (ECT) remains the one of the most effective of biological antidepressant interventions. However, the exact neurobiological mechanisms underlying the efficacy of ECT remain unclear. A gap in the literature is the lack of multimodal research that attempts to integrate findings at different biological levels of analysis METHODS: We searched the PubMed database for relevant studies. We review biological studies of ECT in depression on a micro- (molecular), meso- (structural) and macro- (network) level.
Results:
ECT impacts both peripheral and central inflammatory processes, triggers neuroplastic mechanisms and modulates large scale neural network connectivity.
Conclusions:
Integrating this vast body of existing evidence, we are tempted to speculate that ECT may have neuroplastic effects resulting in the modulation of connectivity between and among specific large-scale networks that are altered in depression. These effects could be mediated by the immunomodulatory properties of the treatment. A better understanding of the complex interactions between the micro-, meso- and macro- level might further specify the mechanisms of action of ECT.
Objective:
Identifying biomarkers associated with response to electroconvulsive therapy (ECT) may aid clinical decisions. The authors examined whether greater polygenic liabilities for major depressive disorder, bipolar disorder, and schizophrenia are associated with improvement following ECT for a major depressive episode.
Methods:
Between 2013 and 2017, patients who had at least one treatment series recorded in the Swedish National Quality Register for ECT were invited to provide a blood sample for genotyping. The present study included 2,320 participants (median age, 51 years; 62.8% women) who had received an ECT series for a major depressive episode (77.1% unipolar depression), who had a registered treatment outcome, and whose polygenic risk scores (PRSs) could be calculated. Ordinal logistic regression was used to estimate the effect of PRS on Clinical Global Impressions improvement scale (CGI-I) score after each ECT series.
Results:
Greater PRS for major depressive disorder was significantly associated with less improvement on the CGI-I (odds ratio per standard deviation, 0.89, 95% CI=0.82, 0.96; R2=0.004), and greater PRS for bipolar disorder was associated with greater improvement on the CGI-I (odds ratio per standard deviation, 1.14, 95% CI=1.05, 1.23; R2=0.005) after ECT. PRS for schizophrenia was not associated with improvement. In an overlapping sample (N=1,207) with data on response and remission derived from the self-rated version of the Montgomery-Åsberg Depression Rating Scale, results were similar except that schizophrenia PRS was also associated with remission.
Conclusions:
Improvement after ECT is associated with polygenic liability for major depressive disorder and bipolar disorder, providing evidence of a genetic component for ECT clinical response. These liabilities may be considered along with clinical predictors in future prediction models of ECT outcomes.
Background
An increased risk of manic episodes has been reported in patients with neurodegenerative disorders, but the clinical features of bipolar disorder (BD) in different subtypes of dementia have not been thoroughly investigated. Objectives: The main aim of this study is systematically review clinical and therapeutic evidence about manic syndromes in patients with Alzheimer’s disease (AD), vascular dementia (VD), and frontotemporal dementia (FTD). Since manic-mixed episodes have been associated with negative outcomes in patients with dementia and often require medical intervention, we also critically summarized selected studies with relevance for the treatment of mania in patients with cognitive decline. Methods: A systematic review of the literature was conducted according to PRISMA guidelines. PubMed, Scopus and Web of Science databases were searched up to February 2022. Sixty-one articles on patients with AD, VaD or FTD and BD or (hypo)mania have been included. Results: Manic symptoms seem to be associated with disease progression in AD, have a greatly variable temporal relationship with cognitive decline in VaD, and frequently coincides with or precedes cognitive impairment in FTD. Overall, mood stabilizers and electroconvulsive therapy may be the most effective treatments, while the benefits of short-term treatment with antipsychotic agents must be balanced with the associated risks. Importantly, low-dose lithium salts may exert a neuroprotective activity in patients with AD.
Conclusion
Prevalence, clinical features and treatment response to pharmacotherapy of manic syndromes in patients with dementia may be differentially affected by the nature of the underlying neurodegenerative conditions.
Objectives: Judging that the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria for defining mania/hypomania (and thus bipolar I/II disorders, respectively) would benefit from review, we formed an expert taskforce to derive modified criteria for consideration. The aim of this paper is to summarise the component stages and detail the final recommended criteria.
Methods: We first sought taskforce members’ views on the Diagnostic and Statistical Manual of Mental Disorders criteria and how they might be modified. Next, members recruited patients with a bipolar I or II disorder, and who were asked to judge new definitional options and complete a symptom checklist to determine the most differentiating items. The latter task was also completed by a small comparison group of unipolar depressed patients to determine the mood state items that best differentiate unipolar from bipolar subjects. Subsequent reports overviewed analyses arguing for bipolar I and II as being categorically distinct and generated empirically derived diagnostic criteria.
Results: Alternatives to all the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria were generated. Modifications included recognising that impairment is not a necessary criterion, removing hospitalisation as automatically assigning bipolar I status, adding an irritable/angry symptom construct to the symptom list, deleting a mandatory duration period for manic/hypomanic episodes, and requiring a greater number of affirmed symptoms for a bipolar diagnosis to manage the risk of overdiagnosis. Granular symptom criteria were identified by analyses and constructed to assist clinician assessment. A potential bipolar screening measure was developed with analyses showing that it could clearly distinguish bipolar versus unipolar status, whether symptom items were assigned as having equal status or weighted by their quantified diagnostic contribution.
Conclusion: While requiring further validation, we suggest that the revised criteria overcome several current Diagnostic and Statistical Manual of Mental Disorders (5th ed.) limitations to defining and differentiating the two bipolar sub-types, while still respecting and preserving the Diagnostic and Statistical Manual of Mental Disorders template. It will be necessary to determine whether the bipolar screening measure has superiority to currently accepted measures.
Objectives:
The character and duration of cognitive adverse effects of electroconvulsive therapy (ECT) are unclear. This study investigated (1) the sensitivity of a short cognitive test battery to cognitive adverse effects of ECT, (2) the relation between subjective and objective cognitive adverse effects, and (3) patient characteristics associated with more subjective than objective adverse effects.
Methods:
Forty-one patients with unipolar or bipolar depression referred to ECT underwent assessments at baseline, 5 to 7 days post-ECT, and 3 months post-ECT. Patients rated their fear of various aspects of ECT on a visual analog scale. At each assessment, patients were evaluated for depressive symptoms, completed the Screen for Cognitive Impairment in Psychiatry (SCIP) and Trail Making Test-Part B (TMT-B), and rated their cognitive difficulties.
Results:
Patients feared cognitive adverse effects and lack of treatment efficacy more than other aspects of ECT. The SCIP and TMT-B revealed transient decline in objective cognition after ECT, which was reversed after 3 months. Patients presented with more subjective than objective cognitive difficulties at baseline and more subjective than objective cognitive adverse effects of ECT. This discrepancy was significantly reduced at follow-up. Younger age and poorer objective cognition pretreatment were associated with more subjective than objective cognitive adverse effects 5 to 7 days after ECT.
Conclusions:
The SCIP and TMT-B are sensitive to cognitive adverse effects of ECT. Patients show more subjective than objective cognitive adverse effects of ECT. These insights can be used clinically to inform patients of treatment choice and expected cognitive consequences.
Episode chronicity and medication failure are considered robust predictors of poor response to electroconvulsive therapy (ECT). In this study we explored the associations between indexes of drug exposure during current episode and outcomes of ECT in 168 bipolar depressive patients. The association between response or remission and number of previous pharmacological trials, failure of treatment with antidepressants, antipsychotics or combinations, and sum of maximum Antidepressant Treatment History Form (ATHF) scores obtained in each pharmacological class were tested. 98 patients (58%) were considered responders and 21 remitters (13%). Number of trials, number of adequate trials, ATHF sum, antidepressant-antipsychotic combination therapy failure and failure of two adequate trials were significantly negatively associated with remission. The association with ATHF sum stayed significant when controlling for episode duration and manic symptoms and survived stepwise model selection. No significant associations with response were identified. In conclusion, a history of multiple drug treatments may be linked to a greater resistance to all types of therapies, including ECT. However, we could not exclude that, at least in some patients, a prolonged exposure to pharmacological treatments may be responsible for a greater chronicity and for the presence of residual symptoms, which would explain reduced remission after ECT.
Objectives:
Electroconvulsive therapy (ECT) is a well-established treatment for mood disorders in younger adults and has been consistently shown to be safe and effective in unipolar depression in older adults. However, data on this treatment in older adults with bipolar disorder are limited. In this retrospective study, we report outcomes from all cases of older adults with bipolar depression who received ECT from a large academic institution over a 7-year period.
Methods:
We retrospectively identified all patients 65 years and older with bipolar depression who were treated with ECT over a 7-year period. Patients receiving ECT for an episode of bipolar depression were included in the study based on chart review and availability of documented outcome measures. Primary outcomes were changes in Montreal Cognitive Assessment and Clinical Global Impressions scores.
Results:
We identified 34 patients meeting inclusion criteria. Collectively, patients had statistically significant improvement in Montreal Cognitive Assessment scores and reductions in Clinical Global Impressions severity scores after treatment. Pre- and posttreatment Montgomery-Asberg Depression Rating Scale scores were also available for a subset of 20 patients and demonstrated a similarly significant reduction in severity with treatment. There were no serious adverse effects of treatment, and no patients discontinued treatment.
Conclusions:
Electroconvulsive therapy was well tolerated and effective in treating bipolar depression in older adults. Importantly, these findings challenge commonly held worries about cognitive decline in older adults receiving ECT. It should be a regular consideration for management of this challenging illness in a population that may otherwise not respond to pharmacotherapy.
Objective: Several clinical variables assumed to be predictive of electroconvulsive therapy (ECT) outcome in major depressive disorder show substantial interrelations. The current study tries to disentangle this interdependence to distill the most important predictors of treatment success to help improve patient-treatment matching.
Methods: We constructed a conceptual framework of interdependence capturing age, episode duration, and treatment resistance, all variables associated with ECT outcome, and the clinical symptoms of what we coin core depression, ie, depression with psychomotor agitation, retardation, psychotic features, or a combination of the three. The model was validated in a sample of 73 patients with a major depressive episode according to DSM-5 treated twice weekly with ECT (August 2015-January 2018) using path analyses, with the size and direction of all direct and indirect paths being estimated using structural equation modeling. Reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores during treatment was the ECT outcome measure.
Results: The baseline presence of psychomotor agitation, retardation, and/or psychotic symptoms strongly correlated with beneficial ECT outcome (z = 0.84 [SE = 0.17]; P < .001), and the association between age and the effect of ECT appears to be mediated by their presence (z = 0.53 [SE = 0.18]; P = .004). There was no direct correlation between age and ECT response (P = .479), but there was for episode duration and ECT outcome (z = -0.38 [SE = 0.08]; P < .001).
Conclusions: ECT is a very effective treatment option for severe depressive disorder, especially for patients suffering from severe depression characterized by the presence of psychomotor agitation, psychomotor retardation, psychotic symptoms, or a combination of these 3 features, with the chance of a beneficial outcome being reduced in patients with a longer episode duration. Age may heretofore have been given too much weight in ECT decision making.
Trial registration: ClinicalTrials.gov Identifier: NCT02562846.
Resistance to pharmacological agents is commonly encountered in the treatment of acute episodes of mania. In contemporary practice guidelines, electroconvulsive therapy (ECT), once a widely used standalone intervention for mania, is no longer considered a first-line treatment. Stigma, logistics, and ethical factors constrain ECT administration in this condition and lead to its underutilization. However, the past three decades have produced promising research regarding the use of ECT in mania. Randomized controlled trials, albeit in limited numbers, the adoption of ultrabrief ECT, examination of the safety and efficacy of combining ECT with pharmacological agents, including lithium, and use of ECT as a maintenance strategy have enhanced our understanding of how and when to utilize this intervention in mania. In this comprehensive review, the authors summarize the evidence regarding the efficacy and safety of ECT in mania, including related syndromes, such as delirious mania and mixed affective states. The impact of technical parameters, particularly the choice of treatment frequency, electrode placements, and pulse width, are discussed in the light of recent evidence
Objective
As limitations exist across DSM criteria sets for defining and differentiating the bipolar disorders generally and their component bipolar I (BP‐1) and bipolar II (BP‐II) sub‐types, we sought to generate empirically‐based criteria.
Method
We formed an international Task Force (TF) comprising members with bipolar disorder expertise, and who recruited 74 patients with a TF‐diagnosed bipolar I and 104 with a bipolar II condition (with patients responding to definitional queries and symptom questionnaires), while 33 unipolar depressed patients recruited by the first author also completed the symptom questionnaire. A factor analysis sought to determine granular hypo/manic constructs.
Results
The bipolar disorder subjects strongly affirmed a new general definition of a bipolar disorder (capturing both manic and hypomanic episodes). While DSM‐5 requires impaired functioning, we established that a high percentage of individuals with a BP‐I or a BP‐II disorder reported improved functioning and therefore modified this criterion. Analyses identified those with differential high rates in individuals with bipolar disorder and its sub‐types (and thus not simply capturing happiness), while a factor analysis generated seven symptom constructs both linked with and differing from DSM‐5 bipolar symptom criteria.
Conclusion
This second‐stage report details a new set of criteria for differentiating the bipolar disorders from unipolar depressive conditions, while arguing for BP‐I and BP‐II disorders being differentiated principally by the respective presence or absence of psychotic features. Future studies will evaluate whether further modifications are required and examine for differential treatment benefits for those with a BP‐I versus a BP‐II condition.
Objectives: Clinically useful predictors of response to electroconvulsive therapy (ECT) are warranted, especially in the case of bipolar depression. The aim of this study was to explore the associations between response and its known and putative correlates.
Methods: Six hundred seventy bipolar depressive patients treated with ECT were included in the study. The association between response (CGI-I ≤ 2) and mean seizure duration, number of treatments, age, sex, bipolar subtype, episode duration, HAM-D and YMRS scores, psychomotor disturbances and psychotic symptoms assessed through BPRS-EV were evaluated by means of univariate and multivariate logistic regression models, including quadratic and/or linear effects of continuous variables.
Results: Four hundred eighty three patients (72%) were responders. Among known correlates of
response, significant quadratic effects were found for seizure duration and number of treatments, while a linear association was confirmed for episode duration. Among putative correlates, severe motor retardation, tension or agitation, hyperactivity and delusions of guilt were significantly associated with response (p<.01) and a significant quadratic effect was found for YMRS score (p<.01).
Conclusion: Bipolar depressive patients with severe psychomotor disturbances, mood-congruent
delusions and severe mixed features are highly responsive to ECT. A significant improvement in response prediction is expected when considering those clinical characteristics.
Background
Electroconvulsive therapy (ECT) is an effective treatment for acute depression, mania and mixed states. We evaluated the long-term outcome of patients with bipolar depression or mixed state, responsive to ECT.
Methods
this observational follow-up study was conducted in 70 patients with Bipolar Disorder: 36 patients met DSM-IV-TR criteria for a major depressive episode (MDE) and 34 for a mixed episode (MXE). During the follow-up after ECT, the relapse rates and the duration of response and remission periods were recorded.
Results
the mean duration of the follow-up was 57 weeks. 93% of the patients maintained at least a partial therapeutic response for more than 90% of the follow-up period. 73% of patients fulfilled the criteria for a full remission, 33% showed a depressive relapse and 10% a mixed relapse. No manic relapses occurred but almost 1/3 of the sample presented hypomanic episodes. MDE patients presented higher rates of remission compared to MXE ones. Patients with anxiety disorders reported earlier relapses than those without this comorbidity. Relapsed-patients showed higher functional impairment at baseline evaluation, compared to non-relapsed ones.
Limitations
nonrandom allocation, limited sample size, possible influence of psychopharmacological treatment.
Conclusions
Given several methodological limitations, this study cannot draw definite conclusions but could suggest that in treatment-resistant bipolar patients with severe depression or mixed state, ECT may represent a useful treatment option. Patients with mixed features, comorbid anxiety disorders and higher functional impairment present less favorable outcome. Future research on long-term efficacy of ECT and on clinical predictors of relapse is needed.
Background:
Electroconvulsive therapy (ECT) is the most effective biological treatment for depression. Aside the well-known therapeutic effect on mood symptoms, it has also a unique positive impact on psychomotor agitation and retardation, which are core symptoms of depression. The neurobiology behind these effects, however, remains unclear. The basal ganglia are proposed to be important regions in the pathogenesis of psychomotor symptoms in depression. Since ECT can trigger neuroplasticity in these subcortical nuclei, we speculate that ECT-induced volumetric changes of the basal ganglia will positively influence psychomotor symptoms.
Methods:
Psychomotor symptoms were analyzed in 17 patients with severe depression before and after an acute ECT course using a CORE assessment of the retardation, agitation, and non-interaction domains. The volumes of the caudate, putamen, pallidum, and accumbens regions were determined using magnetic resonance imaging one week before and after ECT.
Results:
Psychomotor functions had improved significantly after ECT and significant volume increases were found for the accumbens region, the putamen, and pallidum. The volume increase of the nucleus accumbens correlated with an improvement of psychomotor retardation, while the volume increase of the pallidum correlated negatively with an improvement of the agitation subscore.
Conclusion:
Our findings support the notion of an association between the impact of ECT on depression-related psychomotor symptoms and volume increases of the accumbens region and pallidum, pointing to the importance of the basal ganglia in the therapeutic effect of ECT on psychomotor functioning.
Electroconvulsive therapy (ECT) results effective in two-thirds of the patients with severe and drug-resistant mixed states. The episode duration is the main predictor of nonresponse. This practice may increase the risk of mood destabilization and chronic complications and may decrease the chance of recovery in many patients. Compared with the burden of neurologic and metabolic side effects associated with long-term use of complex pharmacologic regimens, ECT should be considered a safe option with a very low incidence of severe adverse events and a long-term nondestabilizing effect.
Objective: Ministry of Health of Turkey issued a legislation to use only modified electroconvulsive therapy (ECT) in 2005, and this study aimed to assess satisfaction and attitude of bipolar patients regarding modified and unmodified electroconvulsive therapy.
Methods: A total of 100 patients (50 treated with modified electroconvulsive therapy (M-ECT) and 50 treated with unmodified ECT (UM-ECT) with a diagnosis of Bipolar Disorder (depressive or manic episode) were invited to participate in this study. Patients with euthymic mood were included. Satisfaction and attitude towards ECT were evaluated with a structured attitude questionnaire, and M-ECT and UM-ECT patients, and their subgroups (depressive vs. manic) were compared.
Results: No significant differences were found between M-ECT and UM-ECT groups regarding age, sex, marital status and occupation. The majority of all patients (78%) were satisfied from treatment with ECT and with the outcome (88%), without significant differences between modified and unmodified groups. Forgetfulness (70%) and headaches (57%) occurred in all groups, with the only significant difference in forgetfulness being reported by more manic patients treated with UM-ECT. Depressive and manic patients treated with UM-ECT reported concerns of brain damage and physical harm significantly more frequently. While 86% of patients treated with M-ECT consented to a future treatment, this was significantly less in patients treated with UM-ECT (50%).
Conclusions: Bipolar patients report a high degree of satisfaction treated either with modified or unmodified ECT but there was a significant difference in perception of adverse effects and willingness for receiving ECT in future.
Psychomotor symptoms are core features of melancholic depression. This study investigates whether psychomotor disturbance predicts the outcome of electroconvulsive therapy (ECT) and how the treatment modulates psychomotor disturbance. In 73 adults suffering from major depressive disorder psychomotor functioning was evaluated before, during and after ECT using the observer-rated CORE measure and objective measures including accelerometry and a drawing task. Regression models were fitted to assess the predictive value of melancholic depression (CORE ≥ 8) and the psychomotor variables on ECT outcome, while effects on psychomotor functioning were evaluated through linear mixed models. Patients with CORE-defined melancholic depression (n = 41) had a 4.9 times greater chance of reaching response than those (n = 24) with non-melancholic depression (Chi-Square = 7.5, P = 0.006). At baseline, both higher total CORE scores (AUC = 0.76; P = 0.001) and needing more cognitive (AUC = 0.78; P = 0.001) and motor time (AUC = 0.76; P = 0.003) on the drawing task corresponded to superior ECT outcomes, as did lower daytime activity levels (AUC = 0.76) although not significantly so after Bonferroni correction for multiple testing. A greater CORE-score reduction in the first week of ECT was associated with higher ECT effectiveness. ECT reduced CORE-assessed psychomotor symptoms and improved activity levels only in those patients showing the severer baseline retardation. Although the sample was relatively small, psychomotor symptoms were clearly associated with beneficial outcome of ECT in patients with major depression, indicating that monitoring psychomotor deficits can help personalise treatment.
Background:
DSM-5 and ICD-11 define mixed depression as the presence of non-overlapping symptoms of opposite polarity during a major depressive episode. However, such a definition has generated controversy.
Methods:
2720 patients with major depression, enrolled in BRIDGE–II–MIX cross-sectional study, were subdivided in clusters using a k-medoids algorithm based on 32 clinical features. Clinical variables were compared among clusters. Stepwise logistic regression and random forest predictor importance estimates were used to identify which features best predicted cluster membership. Data-driven criteria were compared with DSM-5 mixed specifier and previously proposed research-based criteria (RBDC).
Results:
Two clusters were identified (MDE+/-MX), mainly reflecting differences in current manic symptoms. As expected, MDE + MX showed higher rates of comorbidities and bipolar features, more previous depressive episodes and suicide attempts, shorter duration of current MDE and lower age at onset. Seven clinical features among the original 32 proved to be the best predictors of cluster membership. Derived criteria perfectly allocated subjects in clusters, requiring at least four features out of the following seven: irritability, emotional lability, psychomotor agitation, distractibility, mood reactivity, absence of reduced appetite, and absence of psychomotor retardation. RBDC showed a better performance than DSM-5 in identifying MDE + MX subjects.
Conclusion:
Our results strongly suggest a predominant role for overlapping “manic” symptoms in defining mixed depressive states. Mixed depression is better identified by the presence of excitatory features shared with mania and atypical features rather than by non-overlapping manic symptoms.
Objective
In this systematic review and meta‐analysis, the response, remission, and speed of response in adults with major depressive disorder (MDD) and bipolar disorder in depressive episode (BDD) receiving an acute course of electroconvulsive therapy (ECT) were quantitatively analyzed.
Methods
Using the PRISMA guidelines, 1660 citations were identified through five electronic databases. 19 articles met final inclusion criteria for meta‐analysis.
Results
The pooled response and remission rates with ECT in MDD were 74.2% (n = 1246/1680) and 52.3% (n = 850/1626), respectively. In BDD, they were 77.1% (n = 437/567) and 52.3% (n = 275/377), respectively. Although response rates to ECT were statistically higher in BDD (OR = 0.73, 95% CI: 0.56–0.95, p = 0.02), remission rates were similar (OR = 0.91, 95% CI: 0.65‐1.26, p = 0.56). Individuals with BDD vs MDD required fewer number of ECT sessions to achieve response (SMD = ‐0.23, 95% CI: ‐0.44‐ ‐0.023, p = 0.03). There were no significant moderator effects identified.
Conclusion
Response rates and speed of response are higher in individuals with BDD, however, remission rates are equivalent. These finding support increased utilization of ECT in individuals with treatment‐refractory BDD.
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Background
Electroconvulsive therapy (ECT) is considered to be the most effective treatment in severe major depression. The identification of reliable predictors of ECT response could contribute to a more targeted patient selection and consequently increased ECT response rates.
Aims
To investigate the predictive value of age, depression severity, psychotic and melancholic features for ECT response and remission in major depression.
Method
A meta-analysis was conducted according to the PRISMA statement. A literature search identified recent studies that reported on at least one of the potential predictors.
Results
Of the 2193 articles screened, 34 have been included for meta-analysis. Presence of psychotic features is a predictor of ECT remission (odds ratio (OR) = 1.47, P = 0.001) and response (OR = 1.69, P < 0.001), as is older age (standardised mean difference (SMD) = 0.26 for remission and 0.35 for response ( P < 0.001)). The severity of depression predicts response (SMD = 0.19, P = 0.001), but not remission. Data on melancholic symptoms were inconclusive.
Conclusions
ECT is particularly effective in patients with depression with psychotic features and in elderly people with depression. More research on both biological and clinical predictors is needed to further evaluate the position of ECT in treatment protocols for major depression.
Declaration of interest
None.
Objective:
Acute course of electroconvulsive therapy is effective in inducing remission from depression, but recurrence rate is unacceptably high following termination of electroconvulsive therapy despite continued pharmacotherapy. Continuation electroconvulsive therapy and maintenance electroconvulsive therapy have been studied for their efficacy in preventing relapse and recurrence of depression. The purpose of this meta-analysis was to examine the efficacy of continuation electroconvulsive therapy and maintenance electroconvulsive therapy in preventing relapse and recurrence of depression in comparison to antidepressant pharmacotherapy alone.
Methods:
We searched MEDLINE, Embase, PsycINFO, clinicaltrials.gov and Cochrane register of controlled trials from the database inception to December 2016 without restriction on language or publication status for randomized trials of continuation electroconvulsive therapy and maintenance electroconvulsive therapy. Two independent Cochrane reviewers extracted the data in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews and meta-analyses. The risk of bias was assessed using four domains of the Cochrane Collaboration Risk of Bias Tool. Outcomes were pooled using random effect model. The primary outcome was relapse or recurrence of depression.
Results:
Five studies involving 436 patients were included in the meta-analysis. Analysis of the pooled data showed that continuation electroconvulsive therapy and maintenance electroconvulsive therapy, both with pharmacotherapy, were associated with significantly fewer relapses and recurrences than pharmacotherapy alone at 6 months and 1 year after a successful acute course of electroconvulsive therapy (risk ratio = 0.64, 95% confidence interval = [0.41, 0.98], p = 0.04, risk ratio = 0.46, 95% confidence interval = [0.21, 0.98], p = 0.05, respectively). There was insufficient data to perform a meta-analysis of stand-alone continuation electroconvulsive therapy or maintenance electroconvulsive therapy beyond 1 year.
Conclusion:
There are only a few randomized trials of continuation electroconvulsive therapy and maintenance electroconvulsive therapy. The preliminary and limited evidence suggests the modest efficacy of continuation electroconvulsive therapy and maintenance electroconvulsive therapy with concomitant pharmacotherapy in preventing relapse and recurrence of depressive episodes for 1 year after the remission of index episode with the acute course of electroconvulsive therapy.
Objective:
To examine the level of agreement across professionally auspiced evidence-based guidelines for managing the bipolar disorders.
Methods:
A literature search in PubMed, the National Guideline Clearinghouse, the Cochrane Database of Systematic Reviews and PsycInfo was undertaken using the search terms 'bipolar disorder' and 'guidelines', generating 11 evidence-based guidelines published by professional organisations over the 2002-2015 period. Each guideline was reviewed by two independent reviewers and key themes extracted via qualitative analyses.
Results:
There was agreement on issues such as the first-line treatment of mania where mood-stabilising and/or an antipsychotic medication together with tapering or ceasing antidepressant medications was most commonly recommended. Differences included the extent to which (i) the different bipolar disorders were defined or not, (ii) there were separate recommendations for bipolar I and bipolar II disorders vs. non-differentiating general bipolar management strategies, (iii) 'general' vs. severity-based recommendations were made, and (iv) narrow vs. broad sets of candidate medications were nominated, while there was variable consideration of treatments such as electroconvulsive therapy (ECT).
Conclusions:
While there was some consistency across guidelines on key recommendations, there was also substantial inconsistencies, limiting the generation of any 'meta-consensus' model for managing the bipolar disorders.
Importance:
Increased activity and energy alongside mood change are identified in the DSM-5 as cardinal symptoms of mania and hypomania. A wide range of existing research suggests that this revision may be valid, but systematic integration of the evidence has not been reported. The term activation is understood as emerging from underlying physiological change and having objective (observable motor activity) and related subjective (energy) levels.
Objectives:
To systematically review studies of the clinical phenomenon of activation in bipolar disorder, to determine whether activation is statistically abnormal in bipolar disorder and demonstrably distinct from mood, and to identify any significant between- and within-individual differences in the dynamics of activation.
Evidence review:
This systematic review of MEDLINE, PsycINFO, EMBASE, CINAHL, and PubMed databases from January 1, 1970, until September 30, 2016, identified 56 of a possible 3284 citations for (1) data-driven analyses of the dimensions and factor structure of mania and bipolar depression and (2) longitudinal studies reporting real-time objective monitoring or momentary assessment of daytime activity in individuals with bipolar disorder compared with other clinical or healthy control samples. Hand search of reference lists, specialty journals, websites, published conference proceedings, and dissertation abstracts and contact with other researchers ensured inclusion of gray literature and additional analyses as well as raw data if appropriate. Quality assessment was perfomed using the National Institutes of Health quality assessment tool.
Findings:
A total of 56 studies met eligibility criteria for inclusion in the review including 29 analyses of the factor structure of bipolar disorder, 3 of activity data from experimental sampling or ecological momentary assessment, and 20 actigraphy and 4 laboratory-based studies. Synthesizing findings across the studies revealed that the most robust finding was that mean levels of activity are lower during euthymia and depression in patients with bipolar disorder compared with healthy controls and other comparison groups (11 studies). The 7 ecological and laboratory studies show less organized or predictable patterns of behavior and a relative lack of habituation among patients with bipolar disorders compared with others. Factor analytic studies provide fairly consistent evidence that mood and activation represent distinct dimensions of bipolar disorder. Ten studies that examined interindividual and intraindividual patterns of activity suggest that mania may be better characterized by differences in robustness, variability, predictability, or complexity of activation rather than mean levels of activity.
Conclusions and relevance:
Within the limitations of the data, this synthesis of available evidence broadly supports the elevation of activation as a criterion A symptom for bipolar disorder in DSM-5. Although the importance of activation in bipolar disorders has been acknowledged for more than a century, this review suggests that this critical construct is understudied and should be the topic of more systematic high-quality research.
Objective:
We evaluated the effectiveness of Electroconvulsive Therapy (ECT) in the treatment of Bipolar Disorder (BD) in a large sample of bipolar patients with drug resistant depression, mania, mixed state and catatonic features.
Method:
522 consecutive patients with DSM-IV-TR BD were evaluated prior to and after the ECT course. Responders and nonresponders were compared in subsamples of depressed and mixed patients. Descriptive analyses were reported for patients with mania and with catatonic features.
Results:
Of the original sample only 22 patients were excluded for the occurrence of side effects or consent withdrawal. After the ECT course, 344 (68.8%) patients were considered responders (final CGIi score ≤3) and 156 (31.2%) nonresponders. Response rates were respectively 68.1% for BD depression, 72.9% for mixed state, 75% for mania and 80.8% for catatonic features. Length of current episode and global severity of the illness were the only statistically significant predictors of nonresponse.
Conclusions:
ECT resulted to be an effective and safe treatment for all the phases of severe and drug-resistant BD. Positive response was observed in approximately two-thirds of the cases and in 80% of the catatonic patients. The duration of the current episode was the major predictor of nonresponse. The risk of ECT-induced mania is virtually absent and mood destabilization very unlikely. Our results clearly indicate that current algorithms for the treatment of depressive, mixed, manic and catatonic states should be modified and, at least for the most severe patients, ECT should not be considered as a "last resort".
Electroconvulsive therapy (ECT) is an effective treatment commonly used for depression and other major psychiatric disorders. We discuss potential adverse effects (AEs) associated with ECT and strategies for their prevention and management. Common acute AEs include headache, nausea, myalgia, and confusion; these are self-limiting and are managed symptomatically. Serious but uncommon AEs include cardiovascular, pulmonary, and cerebrovascular events; these may be minimized with screening for risk factors and by physiologic monitoring. Although most cognitive AEs of ECT are short-lasting, troublesome retrograde amnesia may rarely persist. Modifications of and improvements in treatment techniques minimize cognitive and other AEs.
Sometimes it is more “inward anxiety and trembling,” a painful tension; sometimes it is an anxious restlessness, which finds an outlet in the most varied gestures, in states of violent excitement, and in heedless attempts at suicide. These moods are most frequently found in the periods of transition between states of depression and mania; they are, therefore, probably most correctly regarded as mixed states of depression and manic excitability (Kraepelin, 1913). The inner unrest is the constant thing, while the motor unrest is variable (Lewis, 1934). Introduction The greatest shortcoming of psychiatry is the near complete lack of knowledge of the pathophysiological processes underlying our clinical entities. Kahlbaum (1863) was the first to distinguish clearly between symptomatic clinical pictures and the disease process that was responsible for them. Kraepelin took this concept a step further and based the idea of the disease process (Vorgang) on the conditions under which the disease starts, its course, and outcome. This method of clinical psychiatry achieved the separation of manic-depressive illness from dementia praecox. But the real identity of the pathophysiological process underlying the clinical entities still remains obscure. Our psychiatric nosology is entirely based on phenomenology and course. We do, however, have important tools at our disposal, which are the psychoactive drugs. The response to these drugs not only indicates the pharmacological action of the drug itself but also provides important clues about the nature of the neuropathologic process upon which the drug acts.
Objective:
Roughly one-third of individuals with depression do not respond to electroconvulsive therapy (ECT). Reliable predictors of ECT response would be useful for patient selection, but have not been demonstrated definitively. We used meta-analysis to measure effect sizes for a series of clinical predictors of ECT response in depression.
Data sources:
PubMed was searched systematically to identify studies published after 1980 that tested at least 1 clinical predictor of response to ECT.
Study selection:
Of 51 studies identified, 32 were compatible with meta-analysis.
Data extraction:
The weighted mean odds ratio (OR) or standardized mean difference (SMD) was computed for each of 10 clinical predictors, based on dichotomous outcomes (responder vs nonresponder). Statistical analyses examined robustness, bias, and heterogeneity.
Results:
Shorter depressive episode duration predicted higher ECT response rate (SMD = -0.37, 7 studies, 702 subjects, P = 4 × 10(-6)). History of medication failure in the current episode was also a robust predictor: response rates were 58% and 70%, respectively, for those with and without medication failure (OR = 0.56, 11 studies, 1,175 subjects, P = 1 × 10(-5)). Greater age and psychotic features were weakly associated with higher ECT response rates, but heterogeneity was notable. Bipolar diagnosis, sex, age at onset, and number of previous episodes were not significant predictors. Analyses of symptom severity and melancholic features were inconclusive due to study heterogeneity.
Conclusions:
Longer depressive episodes and medication failure at baseline are robust predictors of poor response to ECT, with effect sizes that are modest but clinically relevant. Patient characteristics used traditionally such as age, psychosis, and melancholic features are less likely to be clinically useful. More robust clinical and biological predictors are needed for management of depressed patients considering ECT.
The aim of this study was to evaluate the effectiveness of continuation and maintenance electroconvulsive therapy (C/M-ECT) in patients with bipolar or schizoaffective disorder.
We reviewed the charts of all patients diagnosed with a bipolar or schizoaffective disorder treated with C/M-ECT from August 2009 until December 2013. We gathered demographic data and treatment variables (electrode placement, stimulus dose, and concomitant use of medication; number of C/M-ECT sessions; and number of new ECT courses). Primary outcome measure was the number of hospitalization days during C/M-ECT as compared with an equal period before starting the index course.
Twenty women (64.5%) and 11 men (35.5%) with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition bipolar disorder (n = 22, 71%) or schizoaffective disorder (n = 9, 29%) received C/M-ECT. The mean (SD) age was 51.23 (14.86; range, 28-74) years. Before the start of the index ECT, patients had a mean of 290 hospitalization days (248.4 days, full hospitalization; 41.6 days, partial hospitalization), whereas during C/M-ECT, they had a mean of 214.7 hospitalization days (85.4 days, full hospitalization; 129.3 days, partial hospitalization). The number of readmissions before ECT was 2.13, whereas during C/M-ECT, it decreased to 1.48. Only the decrease in number of full hospitalization days was significant. Most patients (n = 23, 74.19%) needed an acute course of ECT during M-ECT.
Maintenance ECT seems to significantly reduce the number of full hospitalization days in patients with severe bipolar or schizoaffective disorder.