No Effect of Serum Electrolyte Levels on Electroconvulsive Therapy Seizure Quality Parameters.

INTRODUCTION: Seizure quality is considered to be associated with treatment outcomes of electroconvulsive therapy (ECT). A wide range of treatment parameters and patient characteristics are known to influence seizure quality. However, conflicting results exist for the role of serum electrolyte levels and seizure quality. METHODS: We retrospectively analyzed a total of 454 patients and a total of 2119 individual acute ECT sessions irrespective of diagnosis where a clinical evaluation of serum levels of sodium, potassium, and calcium took place routinely up to 2 days before the ECT session. To assess the impact of serum electrolyte levels on seizure quality parameters, we used mixed-effects linear regression analysis with Bonferroni correction for multiple testing. RESULTS: Serum sodium, potassium, and calcium levels were not associated with seizure quality markers after correcting the significance level for multiple testing. Younger age was consistently associated with higher postictal suppression, interhemispheric coherence, midictal amplitude, and peak heart rate. Lower dose was consistently associated with longer electroencephalogram and motor seizure duration. CONCLUSIONS: Our results suggest that there is no clinically relevant effect of serum electrolyte levels on seizure quality, at least within clinically commonly observed ranges of serum electrolyte concentrations.

Catatonia and ECT across the lifespan.

Electroconvulsive therapy (ECT) is a safe and effective treatment for catatonia with high response rates. Although empirical data suggest that tolerability and efficacy are at least as good as in adults, ECT treatment of children, adolescents, and geriatric patients seems to pose a specific challenge for many practitioners. This article intends to explore and discuss reasons hindering the use of ECT in these patient groups, give an overview on the use of ECT to treat catatonia and provide practical advice on ECT in children, adolescents, and geriatric patients for the treatment of catatonia. Classification of catatonia as a subform of schizophrenia and a diagnostic overlap with other common conditions in children, adolescents, and geriatric patients might lead to underdiagnosis of catatonia. Concerns about the mechanism of action and about a lack of controlled studies as well as general concerns about the use of ECT in children and adolescents might lead to underutilization of ECT. However, studies of ECT to treat catatonia in children, adolescents, and geriatric patients consistently show its safety and effectiveness. Administration of ECT needs to consider some specific characteristics of children, adolescents, and geriatric patients. In conclusion, ECT is a safe and highly effective treatment for catatonia across the lifespan. Existing evidence does not warrant restrictions of its use in certain age groups.

Duration of Electroconvulsive Therapy Postictal Burst Suppression Is Associated With Time to Reorientation.

INTRODUCTION: A burst suppression pattern in the electroencephalogram represents a down-regulated brain state, which also occurs in the postictal phase of electroconvulsive therapy (ECT). Suppressive actions of the brain to terminate the seizure are thought to be necessary for the efficacy of ECT. On the other hand, recent studies showed an association of burst suppression in general anesthesia or sedation with (postprocedural) cognitive complications. METHODS: We retrospectively examined the length of postictal burst suppression and reorientation time in 49 ECT sessions of 25 consecutive patients. Burst suppression duration was determined by bispectral index monitoring and defined as the time with a bispectral index value of less than 20%. The association between duration of burst suppression and reorientation time was analyzed with multivariate logistic and linear regression analysis controlling for several covariates. RESULTS: The reorientation time showed a statistically significant association with the duration of burst suppression, but with no other variable. Longer phase of postictal burst suppression predicted longer reorientation time in the recovery room (P = 0.046). CONCLUSIONS: The association between the duration of postictal burst suppression and reorientation time after ECT in this sample suggests that (not only the efficacy but also the) cognitive adverse effects of ECT might be related to the extent of postictal central inhibition after the termination of the seizure.

Empirical ratio of the combined use of S-ketamine and propofol in electroconvulsive therapy and its impact on seizure quality.

Electroconvulsive therapy (ECT) is an effective treatment for depressive disorders. In certain cases, ECT-associated anaesthesia can be improved by the use of ketofol (i.e., S-ketamine + propofol). We aimed to evaluate the empirical mixing ratio of ketofol in these cases for better clinical implementation. We retrospectively investigated n = 52 patients who received 919 ECT sessions with S-ketamine plus propofol as anaesthetic agents. Several anaesthesia and ECT-related parameters including doses of S-ketamine and propofol were analysed. The mean empirically determined S-ketamine/propofol ratio was 1.38 (SD ± 0.57) for 919 individual ECT sessions and 1.52 (SD ± 0.62) for 52 patients, respectively. The mean relative dose was 0.72 (± 0.18) mg/kg S-ketamine and 0.54 (± 0.21) mg/kg propofol. Higher propofol dose was associated with poorer seizure quality. Seizure quality and time in recovery room were significantly influenced by age. Ketofol could be an option to exploit the advantageous qualities of S-ketamine and propofol, if both doses are reduced compared with single use of S-ketamine or propofol. Patients with poor seizure quality may benefit from lower propofol doses, which are applicable by the addition of ketamine. An empirically determined mixing ratio in favour of ketamine turned out to be preferable in a clinical setting. Recovery time was primarily prolonged by higher age rather than by ketamine dose, which had previously often been associated with a prolonged monitoring time in the recovery room. These new findings could improve electroconvulsive therapy and should be replicated in a prospective manner.

Evaluation of Myocardial Damage After Electroconvulsive Therapy: Analyses of High-Sensitive Cardiac Troponin I and N-Terminal pro-B-type Natriuretic Peptide.

Electroconvulsive therapy (ECT) is a remarkably safe procedure. However, there might exist a subgroup of patients with an increased risk for cardiovascular events. The cardiac-specific enzymes high-sensitive cardiac troponin I (hscTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured before and after ECT in 23 patients. No relevant increase of hscTnI after ECT was found. Mean NT-proBNP levels were higher after ECT and in three patients a new NT-proBNP elevation after ECT was identified. In conclusion, our small study did not find any evidence for myocardial damage due to ECT by measuring hsTnI, but an increase of NT-proBNP, whose clinical relevance could only be speculated, yet.

Electroconvulsive therapy induced gray matter increase is not necessarily correlated with clinical data in depressed patients.

BACKGROUND: Electroconvulsive therapy (ECT) and depression have been associated with brain volume changes, especially in the hippocampus and the amygdala. METHODS: In this retrospective study we collected data from individual pre-post ECT whole brain magnetic resonance imaging scans of depressed patients from six German university hospitals. Gray matter volume (GMV) changes were quantified via voxel-based morphometry in a total sample of 92 patients with major depressive episodes (MDE). Additionally, 43 healthy controls were scanned twice within a similar time interval. RESULTS: Most prominently longitudinal GMV increases occurred in temporal lobe regions. Within specific region of interests we detected significant increases of GMV in the hippocampus and the amygdala. These results were more pronounced in the right hemisphere. Decreases in GMV were not observed. GMV changes did not correlate with psychopathology, age, gender or number of ECT sessions. We ruled out white matter reductions as a possible indirect cause of the detected GMV increase. CONCLUSION: The present findings support the notion of hippocampus and amygdala modulation following an acute ECT series in patients with MDE. These results corroborate the hypothesis that ECT enables primarily unspecific and regionally dependent neuroplasticity effects to the brain.

A novel Seizure Quality Index based on ictal parameters for optimizing clinical decision making in electroconvulsive therapy. Part 1: development.

Early identification of patients at high risk for an unfavorable outcome to ECT during the course might be beneficial because it provides an opportunity for timely intensification or optimization of stimulus conditions. We aimed to develop a new Seizure Quality Index (SQI) that delivers a clinical relevant outcome prediction early in the treatment course and can be used within common clinical setting. An observational study was conducted. Patients (n = 86) with a depressive episode and the clinical decision for ECT (right unilateral, brief pulse) were included, and several ictal parameters derived from the second ECT session and the clinical outcome of the patients were documented. Optimal cut-off points for five different domains of ictal adequacy for younger and older patients for the prediction of "non-response" and "non-remission" based on seizure quality was determined by the Youden Index and a sum score was built. Logistic regression analyses tested the predictive power of derived models. For both outcome variables "non-response" and "non-remission", the logistic regression models were statistically significant, albeit for remission only for subjects below the age of 65 years (χ2 = 17.9, p = 0.001) and (χ2 = 6.4, p = 0.020), respectively. The models correctly classified 87.2% (non-response) and 50.0% (non-remission) of the cases. ROC curve analysis showed an AUC of 0.87 (non-response) and 0.70 (non-remission). In elderly patients (> 65), no such model could be established due to a response rate of 100%. Our data provide promising, clinically relevant results about the prediction of response to ECT at an early stage for patients with depression.

Electroconvulsive therapy enhances the anti-ageing hormone Klotho in the cerebrospinal fluid of geriatric patients with major depression.

Klotho is a humoral factor with pleiotropic effects. Most notably, Klotho deficiency is associated with a phenotype comprising organ manifestations accompanying aging including atherosclerosis and cognitive impairment. Research on the role of Klotho in affective disorder is scarce, which is surprising in light of the fact that depression is associated with accelerated cellular aging as well as aging-related phenotypes and comorbidity observed in Klotho deficiency. On these grounds we investigated Klotho levels in the cerebrospinal fluid (CSF) and serum of eight geriatric patients undergoing electroconvulsive therapy (ECT) for severe depression. We hypothesize that ECT as a highly effective antidepressant treatment leads enhances Klotho levels. We found a significant difference between pre- and post-ECT CSF Klotho (792.5pg/ml vs. 991.3pg/ml, p=0.0020), but no difference in serum Klotho (602.5 vs. 594.3, p=0.32). Moreover, CSF Klotho increase positively correlated with the number of single ECT sessions that were performed in each patient (F1, 6)=7.84, p=0.031). Conjointly, the results of our exploratory study with a small sample size suggest a central nervous system-specific impact of ECT on Klotho, which may in turn partake in mediating the antidepressant effect of ECT. We suggest the modulation of neuroinflammatory processes, which have been ascribed pathophysiological relevance within the conceptual framework of the neuroinflammation hypothesis of depression, through ECT as a potential mechanism by which Klotho is enhanced in response to treatment. Further preclinical and clinical investigation should aim for a precise identification of the role of Klotho in depressive disorder.

Dexmedetomidine for the management of postictal agitation after electroconvulsive therapy with S-ketamine anesthesia.

OBJECTIVES: Postictal agitation (PIA) represents one of the most common complications during a modified electroconvulsive therapy (ECT) course. Its clinical management can be challenging especially in cases with poor response to benzodiazepines. Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist acting predominantly in the locus coeruleus, exerts sedative effects without causing relevant respiratory depression. To the best of our knowledge, this is the first study that aimed to assess the impact of dexmedetomidine use with S-ketamine anesthesia on PIA reduction in ECT. PATIENTS AND METHODS: We retrospectively analyzed 7 patients who underwent 178 ECT sessions with S-ketamine anesthesia between June 2011 and July 2015 at the Central Institute of Mental Health Mannheim. In 101 sessions, the patients received dexmedetomidine in combination with S-ketamine anesthesia. The decision for dexmedetomidine use was based on individual clinical presentation (patients with positive PIA history). A multivariate repeated measurement logistic regression analysis was conducted to investigate the effect of dexmedetomidine use on the occurrence of PIA. We hypothesized that the use of dexmedetomidine reduced the incidence of PIA also in combination with S-ketamine anesthesia. RESULTS: The prevalence of PIA in ECT sessions with dexmedetomidine administration was lower (mean per patient, 34% vs 62%). In the multivariate logistic regression analysis, the use of dexmedetomidine predicted the non-occurrence of PIA in a highly significant manner (P=0.001, z=-3.83, odds ratio =0.011-0.303). CONCLUSION: Adjunctive use of dexmedetomidine to S-ketamine anesthesia in ECT seems to be a promising tool for the management of intractable PIA syndrome.

The "Forgotten" Treatment of Alcohol Withdrawal Delirium With Electroconvulsive Therapy: Successful Use in a Very Prolonged and Severe Case.

OBJECTIVE: Alcohol withdrawal delirium (AWD) is a notorious complication in alcohol withdrawal. Usually, the symptomatic treatment is efficacious; however, some patients show treatment resistance or a prolonged course of AWD. METHOD: We report the case of a patient with a prolonged and severest form of AWD. Even 11 weeks after admission, he received approximately 100 mg diazepam per week to manage the symptoms of withdrawal delirium. RESULTS: A treatment course of electroconvulsive therapy was initiated, which allowed a complete tapering off of benzodiazepines during electroconvulsive therapy without adverse effects. CONCLUSIONS: The reported case might contribute to alternative approaches reserved for severest forms of prolonged AWD.

Electroconvulsive therapy enhances endocannabinoids in the cerebrospinal fluid of patients with major depression: a preliminary prospective study.

Despite the lack of clinical data about the role of the endocannabinoid system (ECS) in affective disorders, preclinical work suggests that the ECS is relevant in both with regard to the etiology of depression as well as the mediation of antidepressant effects. We measured the intraindividual levels of the endocannabinoids N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) in the cerebrospinal fluid of 12 patients suffering from a major depressive episode before and after the antidepressant treatment by electroconvulsive therapy (ECT). AEA was significantly elevated after ECT as compared to baseline. The AEA increase positively correlated with the number of individually performed ECT sessions. Although the sample size was small and confounders were not rigorously controlled for, our finding corroborates preclinical work and should encourage further exploration of the involvement of the ECS in depressive disorder.

Next generation sequencing analysis of patients with familial cervical artery dissection.

BACKGROUND: The cause of cervical artery dissection is not well understood. We test the hypothesis that mutations in genes associated with known arterial connective tissue disorders are enriched in patients with familial cervical artery dissection. PATIENTS AND METHODS: Patient duos from nine pedigrees with familial cervical artery dissection were analyzed by whole exome sequencing. Single nucleotide variants in a panel of 11 candidate genes (ACTA2, MYH11, FBN1, TGFBR1, TGFBR2, TGFB2, COL3A1, COL4A1, SMAD3, MYLK and SLC2A10) were prioritized according to functionality (stop-loss, nonsense, and missense variants with polyphen-2 score ≥0.95). Variants classified as "benign" or "likely benign" in the ClinVar database were excluded from further analysis. For comparison, non-benign stop-loss, nonsense and missense variants with polyphen-2 score ≥0.95 in the same panel of candidate genes were identified in the European non-Finnish population of the ExAC database (n = 33,370). RESULTS: Non-benign Single nucleotide variants in both affected patients were identified in four of the nine cervical artery dissection families (COL3A1; Gly324Ser, FBN1: Arg2554Trp, COL4A1: Pro116Leu, and TGFBR2: Ala292Thr) yielding an allele frequency of 22.2% (4/18). In the comparison group, 1782 variants were present in 33,370 subjects from the ExAC database (allele frequency: 1782/66,740 = 2.7%; p = 0.0008; odds ratio = 14.2; 95% confidence interval = 3.8-52.9). CONCLUSION: Cervical artery dissection families showed enrichment for non-benign variants in genes associated with arterial connective tissue disorders. The observation that findings differed across families indicates genetic heterogeneity of familial cervical artery dissection.

Alcohol Use Disorder as a Possible Predictor of Electroconvulsive Therapy Response.

INTRODUCTION: Two rapidly acting antidepressive treatment forms, namely, electroconvulsive therapy (ECT) and ketamine, possibly share a common mechanism of action primarily involving alterations of neurotransmission (glutamate and γ-aminobutyric acid levels). Because patients receiving ketamine and with a coexistent family history of an alcohol use disorder (AUD) seem to benefit from consistent and longer lasting antidepressive effects, we hypothesized better treatment response in ECT patients with an own history or a family history of an AUD. METHOD: One hundred forty-one psychiatric inpatients with a major depressive episode, who were treated with ECT, were enrolled into this retrospective study. Age, sex, family or personal history of alcohol or benzodiazepine use disorder, ECT response data, and ECT treatment-related data were collected and analyzed with ordinal logistic regression and Fisher exact tests. RESULTS: Twenty-one percent of all patients had their own history of an AUD, 11% had their own history of a benzodiazepine use disorder, and 11% reported on a positive family history of alcohol or benzodiazepine use disorder. The logistic regression analyses revealed that only patient's own history of an AUD predicts a better ECT response (P = 0.031; odds ratio, 2.1; Fisher exact test, P = 0.006). CONCLUSIONS: Within the limitations of a retrospective study, a history of an AUD seems to be a positive predictor for an ECT response in patients experiencing a major depressive episode, which has not been found in 2 earlier studies. Findings are in line with neurobiological hypotheses of excitatory/inhibitory neurotransmitter changes with ketamine and ECT.

Electroconvulsive therapy selectively enhances amyloid ß 1-42 in the cerebrospinal fluid of patients with major depression: A prospective pilot study.

A complex interplay between ß-amyloid (Aß), Alzheimer׳s disease (AD) and major depression disorder (MDD) suggests that patients with MDD have an altered cerebral Aß metabolism and an increased risk of developing AD. In order to elucidate the relationship between antidepressant treatment and Aß metabolism in humans, we performed a study on Aß peptides in the cerebrospinal fluid (CSF) in patients with MDD during electroconvulsive therapy (ECT) as an effective antidepressant treatment. We measured the levels of Aß1-42, Aß1-40 and of tau proteins in the CSF in 12 patients with MDD before and after a course of ECT. Aß1-42 was significantly elevated after the ECT treatment compared to baseline, whereas no difference was found for other peptides and proteins such as Aß1-40, Aß ratio, total tau protein or its phosphorylated form. The most salient finding was, that the increase of Aß1-42 after ECT was found in all patients with clinical response to the treatment, but not in those who did not respond. The number of ECT sessions of each responding patient correlated with the increase of Aß1-42 in the CSF. Our data point towards to a specific antidepressant mechanism which is not based on a general increase of Aß, but seems to involve merely Aß1-42, the isoform with highest amyloidogenic potential. We present the first study in humans demonstrating an isolated mobilization of Aß1-42 in the CSF of patients with depression who respond to an ECT treatment.

Electroconvulsive therapy increases temporal gray matter volume and cortical thickness.

Electroconvulsive therapy (ECT) is a treatment of choice for severe and therapy resistant forms of major depressive episodes (MDE). Temporal brain volume alterations in MDE have been described for more than two decades. In our prospective study we aimed to investigate individual pre-post ECT treatment whole brain gray matter (GM) volume changes (quantified with voxel-based morphometry) in a sample of 18 patients with MDE. In addition, we studied the effect of ECT on voxel-based cortical thickness in cortical brain regions. The most prominent longitudinal GM increases (significant at a whole brain corrected level) occurred in temporal lobe regions. Within specific region of interest analyses we detected highly significant increases of GM in the hippocampus and the amygdala and to a lesser extent in the habenula (left p=0.003, right p=0.032). A voxel based cortical thickness analysis revealed an increase in cortical temporal regions (basically temporal pole and insula) further corroborating our cortical voxel-based morphometry results. Neither GM decreases or white matter increases nor correlations of GM changes with basic psychopathological parameters were detected. We corroborate earlier findings of hippocampal and amygdala GM volume increase following an acute ECT series in patients with MDE. Temporal GM volume increase was significant on a whole brain level and further corroborated by a cortical thickness analysis. Our data widely exclude white matter loss as an indirect cause of GM growth. Our data add further evidence to the hypothesis that ECT enables plasticity falsifying older ideas of ECT induced "brain damaging".

Serum lipid profile changes after successful treatment with electroconvulsive therapy in major depression: A prospective pilot trial.

BACKGROUND: Cholesterol is reduced in depressed patients, however, these patients have a higher risk for cardiovascular diseases. Electroconvulsive therapy (ECT) is a highly effective treatment option for specific forms of depression. Like for other non-pharmacological therapies targeting depression such as psychotherapy or sleep deprivation, there is a lack of evidence about the effects on peripheral lipid parameters. Our objective was to study the impact of ECT as a non-pharmacological treatment on the peripheral lipid pattern in depressive patients. METHOD: Peripheral lipid profile composition before and after a course of ECT was analysed in 27 non-fasting inpatients at a university psychiatric hospital with DSM-IV major depressive episode. For the impact of ECT treatment on each lipid parameter a multivariate repeated measurement regression analysis was performed and computed separately for every dependent variable. RESULTS: Total Cholesterol and the cholesterol subtypes HDL and LDL were increased after the treatment compared to baseline. Apolipoprotein A1 was also increased after ECT, whereas apolipoprotein B was not. Indices for the prediction of cardiovascular diseases were unchanged after successful treatment by ECT. The reduction of depressive psychopathology negatively correlated with increases of HDL cholesterol and apolipoprotein A1. LIMITATIONS: Subjects received several antidepressants and other psychotropic medication before and during the ECT. CONCLUSIONS: In our preliminary pilot study ECT as a non-pharmacological, effective treatment of depression led to distinct effects on the peripheral lipid pattern.

Focus on ECT seizure quality: serum BDNF as a peripheral biomarker in depressed patients.

Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment in severest or drug-resistant affective disorders. The potential relation between any peripheral biological marker and the seizure quality as a surrogate for treatment efficacy has not been investigated so far. We prospectively examined serum brain-derived neurotrophic factor (BDNF) levels in 20 patients with major depression before and after electroconvulsive therapy. A seizure quality sum score for every ECT session was build up on the basis of the seizure duration, seizure amplitude, central inhibition, interhemispheric coherence and sympathetic activation. Serum BDNF levels were significantly higher after ECT (P = 0.036). In the linear regression analysis, a significant correlation of the serum BDNF levels and the time between the last ECT and the blood withdrawal (P = 0.01) was observed. The ANOVA revealed a significant influence of the interval between the last ECT and the blood withdrawal (P = 0.0017) as well as the seizure quality (P = 0.038) on the variance of BDNF serum levels. Our data corroborate the neurotrophin hypothesis suggesting an ECT-induced central BDNF rise leading to a delayed (>6 days) and increased equilibrium of the peripheral BDNF. The association of seizure adequacy with a BDNF rise might underline the importance of monitoring seizure quality markers in daily practice.