Ketamine or ECT? What Have We Learned From the KetECT and ELEKT-D Trials?

1. Two recent clinical trials, KetECT and ELEKT-D, compared the effectiveness of ketamine and electroconvulsive therapy (ECT) for major depressive disorder. Notably, these trials reported marked differences in ECT's clinical outcomes of, with remission rates of 63% for KetECT and a strikingly lower rate of 22% for ELEKT-D, while the remission rates for ketamine were 46% and 38%, respectively. Considering that the primary objective of both trials was to compare the standard treatment (ECT) with an experimental intervention (ketamine), it is crucial to highlight the pronounced disparities in ECT's clinical outcomes. This article offers a comprehensive comparison of these trials while also exploring how patient characteristics, treatment protocols, and study designs may contribute to such pronounced outcome discrepancies. These differences highlight the heterogeneous nature of depression and underscore the need for personalized treatments. These studies also provide valuable insights into identifying the most suitable candidates for ketamine and ECT.

Electroconvulsive therapy related anxiety in patients with depression: The influence of cognitive coping styles.

INTRODUCTION: Electroconvulsive therapy (ECT) related anxiety (ERA) is a common phenomenon with high individual variability. The way patients cognitively cope with the prospects of receiving ECT could be a mechanism explaining individual differences in ERA. Cognitive coping like monitoring (information seeking, paying attention to consequences) and blunting (seeking distraction and reassurance) has been linked to anxiety in various medical settings, with monitoring leading to more and blunting to less anxiety. How cognitive coping is related to ERA, is unknown. METHODS: The sample consisted of 71 patients with unipolar or bipolar depression referred for ECT. Cognitive coping was assessed at baseline, while ERA was measured each morning before the ECT session. Using a Linear Mixed Model, the influence of cognitive coping styles on ERA was investigated. RESULTS: Blunting was associated with lower levels of ERA (p = 0.037) and monitoring tended to be associated with higher levels of ERA (p = 0.057) throughout the ECT course. Patients with a depression with psychotic features scored significantly higher on monitoring, but even after controlling for monitoring they showed a stronger decline in ERA during treatment compared to patients without psychotic features. CONCLUSION: Cognitive coping style contributes to individual differences in ERA. Blunting is a protective factor, leading to lower levels of ERA throughout the ECT course. On the contrary, patients with a higher monitoring style tend to experience higher levels of ERA. Further insights in these coping mechanisms may help to tailor future treatment to individual patients and reduce ERA before and during ECT treatment.

Vagus Nerve Stimulation as an Alternative to Maintenance Electroconvulsive Therapy for Difficult-to-Treat Depression.

ABSTRACT: Vagus nerve stimulation (VNS), an implantable neurostimulator, provides a valuable long-term treatment option for patients with difficult-to-treat depression. It has been reported that previous response to electroconvulsive therapy (ECT) might predict a better response to VNS and that VNS could reduce or eliminate the need for maintenance ECT in some patients. We present the case of a patient who received a total of more than 120 sessions of ECT over the course of 13 years because of a major depressive disorder, with favorable response but without achieving full remission. After implantation of VNS, ECT was discontinued, and her depressive symptoms improved, achieving remission within 12 months. This case supports VNS as an alternative to maintenance ECT in patients with difficult-to-treat depression who have shown previous response to ECT treatment.

The Cortisol Awakening Response as a Biomarker for Cognitive Side-Effects of Electroconvulsive Therapy.

OBJECTIVE: To test whether the cortisol awakening response (CAR) could be a biomarker for cognitive decline during electroconvulsive therapy (ECT). METHODS: We studied 50 older patients with depression who were treated with ECT from the MODECT cohort. We used linear regression analyses to examine the association between CAR and cognitive change, assessed by the change in Mini Mental State Examination scores between baseline and 1 week after ECT course. CAR was assessed by the area under the curve of cortisol levels, according to Pruessner's-formula. Associations were adjusted for putative confounders, based on previous literature and availability. RESULTS: We found no significant associations between the CAR and cognitive change during the ECT course in (un)adjusted models. CONCLUSION: Our results indicate that the CAR is not usable as a biomarker for ECT-induced cognitive decline during ECT course. Further research in cohorts with larger samples is needed.

Asystole During Electroconvulsive Therapy: Does Electrode Placement Matter? A Systematic Review.

ABSTRACT: Asystole presenting at the start of electrical stimulus application during electroconvulsive therapy (ECT) is a relatively common occurrence. It is most likely caused by vagal nerve stimulation, affecting autonomic cardiac tone. This article reviews the effect of the electrode placement (EP) on the incidence and severity of bradycardia and asystole. A systematic literature review was conducted using the Embase and PubMed databases, up to September 2021, searching for studies evaluating the effect of EP on bradycardia and/or asystole during ECT. Nine case reports describing asystole in patients receiving ECT almost exclusively reported the association with bitemporal (BT) EP. One small descriptive study found no significant effect of EP on cardiac pauses. The results from 4 cohort studies, however, suggest that a right unilateral placement bears a higher risk for developing bradycardia and asystole than BT and bifrontal ECT. The available evidence suggests that right unilateral ECT holds a greater risk for the development of bradycardia and asystole than BT and bifrontal EP.

Borderline Personality Disorder and Outcome of Electroconvulsive Therapy in Patients With Depression: A Systematic Review.

ABSTRACT: Major depressive disorder (MDD) commonly coincides with borderline personality disorder (BPD), aggravating depressive symptom severity and reducing the odds of responding to antidepressant treatments. In this systematic review, we summarize the available evidence assessing the question whether the presence of BPD reduces the response to electroconvulsive therapy (ECT) in individuals with MDD.We conducted a systematic literature search (up to December 2021) without language restriction, using the PubMed/MEDLINE, Web of Science (Core Collection), Embase, and Cochrane Library databases, for prospective and retrospective studies, which assessed the efficacy of ECT in patients with MDD and comorbid BPD.Of the 2548 records screened, 6 articles were selected, 2 of which were based on the same population, leading to 5 included articles. The included studies are reporting on 3465 patients with MDD, of which 1206 had a comorbid BPD. Five of the 6 studies found a less robust response to ECT in patients with MDD and BPD compared with those without BPD.Our results suggest that, in patients with MDD, the presence of BPD is associated with a less robust acute response to ECT. Patients with BPD, however, showed a significant response to ECT in all of the included studies. More longitudinal studies with higher accuracy in BPD diagnosis are needed. Although a comorbid BPD seems to decrease the efficacy of ECT for MDD, ECT remains an effective treatment option in this severely ill patient group.

Knowledge and Attitudes of First- and Final-Year Medical Students about Electroconvulsive Therapy: The Impact of Media.

OBJECTIVE: The aim of this study is to evaluate medical students' knowledge about and attitudes towards electroconvulsive therapy (ECT) and to assess the impact of information sources (including those within and outside the curriculum) on knowledge and attitudes by comparing first- and final-year medical students. METHODS: Two hundred and ninety-five first-year and one hundred forty-nine final-year medical students of the University of Leuven (KU Leuven) in Belgium responded to an anonymous self-administered survey which consisted of questions about sociodemographic background, self-perceived knowledge about medicine, psychiatry and ECT, interest in psychiatry, experience with psychiatric disorders, information sources of ECT, and knowledge about and attitudes towards ECT. RESULTS: Compared to first-year medical students, final-year students had better knowledge about and more positive attitudes towards ECT, partially explained by differences in information sources. Nevertheless, both student groups showed an average knowledge score below 50%. Whereas freshmen attributed their knowledge to movies or documentaries, senior students gained knowledge mainly at university courses, scientific journals, and attending live ECT sessions. A significant positive correlation was found between knowledge about and positive attitudes towards ECT. CONCLUSIONS: The knowledge of first- and final-year medical students remains limited, potentially due to limited instruction about ECT in medical courses. The use of media as an information source predicted negative attitudes towards ECT. Therefore, the stigma and misinformation provided in the media need to be addressed in the medical curriculum.

Impact of Inflammation on Cognitive Functioning After Electroconvulsive Therapy in Older Patients with Depression with and Without White Matter Hyperintensities.

OBJECTIVE: Should we treat older, patients with depression with white matter hyperintensities (WMH) with electroconvulsive therapy (ECT)? WMH, inflammation, depression and cognitive functioning are suggested to be intertwined. Hence, this study investigates whether the association between inflammation and cognition is different in patients with depression with or without WMH. METHODS: Cognitive functioning was assessed using the Mini-Mental State Examination during and after a course of ECT in 77 older patients with depression. Serum samples (C-reactive protein [CRP], interleukin-6 [IL-6], interleukin-10 [IL-10] and tumour necrosis factor-alpha [TNF-α]) and 3T magnetic resonance imaging were obtained prior to ECT. RESULTS: An interaction effect was found for IL-10, but not for CRP, IL-6 or TNF-α. CONCLUSION: In general, the association between inflammatory markers and cognition in patients with depression treated with ECT is not different in patients with WMH compared to patients without WMH.

Long-term Outcome Following Electroconvulsive Therapy for Late-Life Depression: Five-Year Follow-up Data From the MODECT Study.

OBJECTIVE: Electroconvulsive therapy (ECT) is the most effective treatment for late-life depression (LLD). Research addressing long-term outcome following an acute course of ECT for LLD is limited. We aimed to describe relapse, cognitive impairment and survival 5 years after a treatment with ECT for severe LLD, and assess the association of clinical characteristics with all three outcome measures. METHODS: This cohort study was part of the Mood Disorders in Elderly treated with ECT (MODECT) study, which included patients aged 55 years and older with major depressive disorder. Data regarding clinical course, cognitive impairment and mortality were collected 5 years after the index ECT course. We used multivariable Cox proportional hazards models and logistic regression models to assess the association of clinical characteristics with relapse and survival, and cognitive impairment, respectively. RESULTS: We studied 110 patients with a mean age of 72.9 years. 67.1% of patients who showed response at the end of the index ECT course relapsed, and the included clinical characteristics were not significantly associated with the risk of relapse. 38.8% of patients with available data showed cognitive impairment at five-year follow-up. 27.5% were deceased; higher age and a higher number of previous psychiatric admissions were significantly associated with increased risk of mortality. CONCLUSIONS: Five-year outcome after a course of ECT for severe LLD seems to be in line with long-term outcome following other acute treatments for severe LLD in terms of relapse, cognitive impairment and survival. Additional studies aimed at improving long-term outcome in severe LLD are warranted.

ECT-related anxiety during maintenance ECT: A prospective study.

OBJECTIVE: Despite the established safety of electroconvulsive therapy (ECT), ECT-related anxiety (ERA) remains one of the most distressing complications of ECT. ERA is reported to diminish during an acute course of ECT, but it was never studied during maintenance ECT (M-ECT). Our aim was to study the trajectories of ERA during M-ECT and how they differ from trajectories during the acute course. METHODS: Thirty-nine patients with unipolar or bipolar depression, retained for M-ECT after an acute ECT course, were included. ERA was assessed the morning before each ECT session using the ECT-related Anxiety Questionnaire (ERAQ). RESULTS: ERA remained stable during M-ECT (RC = -0.05 (SE = 0.06), t(8.35) = -0.86, p = 0.42), while ERA declined significantly during the acute course (RC = -0.85 (SE = 0.30), t(33.6) = -2.81, p = 0.0082). During the acute course, patients with a psychotic depression were more anxious at baseline (t(32)= -2.42, p = 0.02), and showed a significant decline in ERAQ scores (RC = -1.65 (SE = 0.46), t(31.6) = -3.56, p = 0.0012), whereas patients with a non-psychotic depression were less anxious at baseline and retained stable ERAQ scores during the acute course (RC = -0.06 (SE = 0.41), t(32.1) = -0.14, p = 0.89). Whereas a correlation (r = 0.48) was noticed between the decline of depression severity and ERA during the acute course, this was not the case during M-ECT. CONCLUSION: ERA runs a stable course during M-ECT, after having decreased during the acute course. During the acute course, ERA trajectories differed significantly between patients with a psychotic and non-psychotic depression. Decline of depression severity and ERA are significantly connected during the acute course of ECT. Both depression severity and ERA remain stable during M-ECT.

Suicidal ideation and ECT, ECT and suicidal ideation: A register study.

OBJECTIVE: Although electroconvulsive therapy (ECT) is anti-suicidal, it is not known whether the presence of suicidal ideation (SI) at baseline predicts response and remission after ECT. The aim of the study was to analyze the impact of baseline SI on response and remission following ECT treatment in a large sample of patients with depression and to assess SI before and after ECT. METHODS: This population-based register study used data from the Swedish National Quality Register for ECT and the Swedish Patient Register. Patients aged 18 years or older who had received ECT for a unipolar or bipolar depressive episode between 2011 and 2018 were included in the study. SI was defined as a score of ≥4 on the last item of the Montgomery-Åsberg Depression Rating Scale - Self Assessment (MADRS-S). Using a logistic regression model, SI at baseline was used to predict response and remission following ECT, while controlling for depression severity, psychotic symptoms, presence of a comorbid personality disorder, age, sex, electrode position, unipolar or bipolar disorder, and number of previous suicide attempts at baseline. RESULTS: In patients who exhibited SI at baseline, 53.7% (N = 632) of cases showed a response to ECT, whereas 68.4% (N = 690) of patients without SI showed a response. In addition, 27.2% (N = 320) of cases with SI achieved remission, whereas 48.5% (N = 489) of cases without SI achieved remission. The odds of achieving response and remission for patients with SI were 0.75 and 0.58 times, respectively, those for patients without SI. Of the 1178 patients with pre-treatment SI, 75.64% (N = 891) exhibited no SI at the end of treatment. Moreover, in this subgroup, the presence of a personality disorder, higher MADRS-S-score, and younger age were associated with persistent SI. CONCLUSION: The presence of SI was associated with lower ECT response and remission rates. Nevertheless, depressive symptoms and SI were reduced in a large proportion of patients across both patient groups. Clinicians should be aware of the lower likelihood of achieving a successful outcome following ECT in younger patients who present with a non-psychotic depressive episode, SI, and (suspected) personality disorders. More research is warranted regarding if these patients can achieve similar or better results with other treatments.

The Effect of Electroconvulsive Therapy on Positive Affect and Hedonism in Patients With Depression: A Prospective Study.

OBJECTIVES: The outcome of antidepressant treatments is generally assessed with standardized symptom scales such as the Quick Inventory of Depressive Symptomatology-Clinician Rating (QIDS-C). These scales, however, might not reflect patients' expectations for treatment, including a recovery of positive affect (PA) and hedonism. The Leuven Affect and Pleasure Scale (LAPS) was developed to better reflect patients' expectations for treatment. We used the LAPS to investigate changes in PA and hedonism alongside depressive symptoms during electroconvulsive therapy (ECT) and over 12 weeks after treatment. METHODS: Fifty-three patients with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, depressive episode, referred for ECT, were included in this prospective study. The LAPS and QIDS-C were administered before and 1 and 12 weeks after the ECT course. LAPS normative levels were obtained in 149 healthy controls. RESULTS: Pearson correlations revealed only moderate overlap of the QIDS-C with PA and hedonism. Piecewise linear mixed models indicated significant improvements in depressive symptoms (QIDS-C and LAPS negative affect), PA, and hedonism during ECT. In the 12 weeks after ECT treatment, negative affect and QIDS-C further improved, but PA and hedonism plateaued. Exploratory analyses indicated that only fully remitted patients (QIDS-C) attained normative levels on PA and hedonism at 12 weeks after ECT. CONCLUSIONS: Standardized symptom scales (QIDS-C) may incompletely reflect clinical change in ECT treatment for depression. Although ECT improved depressive symptoms, PA, and hedonism in patients with depression, only fully remitted patients attained normative levels of PA and hedonism, due to plateaus in improvement. These plateaus were not observed for depressive symptoms, which further improved after ECT discontinuation.

Preliminary Assessment of Pre-Electroconvulsive Therapy Evaluation Practices in European Countries: The Need for Guidelines.

OBJECTIVES: Pre-electroconvulsive therapy (ECT) evaluation is an essential part of ECT preparation, a standard treatment in the psychiatric field. However, no routine pre-ECT evaluation has been published so far. This preliminary study aimed to explore different practices in pre-ECT evaluation across European countries. METHODS: The data were collected as a snowball sample approach using an online survey from September 2019 to April 2020. The final analysis included data from 18 clinics placed in 16 European countries. RESULTS: Regulations on the pre-ECT evaluation were found in 9 countries. All clinics reported doing complete blood count, serum electrolytes, and renal function analysis as a part of regular laboratory testing, alongside with a cardiovascular assessment. Ten clinics reported using psychiatric scales. Six clinics reported doing a cognitive assessment, of which all had regulations on the pre-ECT evaluation. Not one evaluation had the same sets of procedures and diagnostics. CONCLUSIONS: The differences in assessment approaches mirror high variability of the pre-ECT evaluation practice across Europe. Cognitive assessment and objectification of psychiatric symptoms should be a regular part of the pre-ECT evaluation because of the monitoring of the most common adverse effect and observing the clinical response to ECT. Standardization of the pre-ECT evaluation and ECT in general would remove criticisms and opposition to the treatment, make it based on the best of our knowledge, and provide a method respectful of patients' best interests and rights.

Electroconvulsive therapy for depression: 80 years of progress.

Electroconvulsive therapy is the most effective treatment for severe, psychotic or treatment-resistant depression. However, its effectiveness continues to be questioned, both in mainstream media and narratives within the scientific literature. In this analysis, we use an evidence-based approach to demonstrate the efficacy and safety of modern electroconvulsive therapy.

Elevated body weight modulates subcortical volume change and associated clinical response following electroconvulsive therapy.

Background: Obesity is a frequent somatic comorbidity of major depression, and it has been associated with worse clinical outcomes and brain structural abnormalities. Converging evidence suggests that electroconvulsive therapy (ECT) induces both clinical improvements and increased subcortical grey matter volume in patients with depression. However, it remains unknown whether increased body weight modulates the clinical response and structural neuroplasticity that occur with ECT. Methods: To address this question, we conducted a longitudinal investigation of structural MRI data from the Global ECT-MRI Research Collaboration (GEMRIC) in 223 patients who were experiencing a major depressive episode (10 scanning sites). Structural MRI data were acquired before and after ECT, and we assessed change in subcortical grey matter volume using FreeSurfer and Quarc. Results: Higher body mass index (BMI) was associated with a significantly lower increase in subcortical grey matter volume following ECT. We observed significant negative associations between BMI and change in subcortical grey matter volume, with pronounced effects in the thalamus and putamen, where obese participants showed increases in grey matter volume that were 43.3% and 49.6%, respectively, of the increases found in participants with normal weight. As well, BMI significantly moderated the association between subcortical grey matter volume change and clinical response to ECT. We observed no significant association between BMI and clinical response to ECT. Limitations: Because only baseline BMI values were available, we were unable to study BMI changes during ECT and their potential association with clinical and grey matter volume change. Conclusion: Future studies should take into account the relevance of body weight as a modulator of structural neuroplasticity during ECT treatment and aim to further explore the functional relevance of this novel finding.

Transient Cognitive Impairment and White Matter Hyperintensities in Severely Depressed Older Patients Treated With Electroconvulsive Therapy.

BACKGROUND: Although electroconvulsive therapy (ECT) is a safe and effective treatment for patients with severe late life depression (LLD), transient cognitive impairment can be a reason to discontinue the treatment. The aim of the current study was to evaluate the association between structural brain characteristics and general cognitive function during and after ECT. METHODS: A total of 80 patients with LLD from the prospective naturalistic follow-up Mood Disorders in Elderly treated with Electroconvulsive Therapy study were examined. Magnetic resonance imaging scans were acquired before ECT. Overall brain morphology (white and grey matter) was evaluated using visual rating scales. Cognitive functioning before, during, and after ECT was measured using the Mini Mental State Examination (MMSE). A linear mixed-model analysis was performed to analyze the association between structural brain alterations and cognitive functioning over time. RESULTS: Patients with moderate to severe white matter hyperintensities (WMH) showed significantly lower MMSE scores than patients without severe WMH (F(1,75.54) = 5.42, p = 0.02) before, during, and post-ECT, however their trajectory of cognitive functioning was similar as no time × WMH interaction effect was observed (F(4,65.85) = 1.9, p = 0.25). Transient cognitive impairment was not associated with medial temporal or global cortical atrophy (MTA, GCA). CONCLUSION: All patients showed a significant drop in cognitive functioning during ECT, which however recovered above baseline levels post-ECT and remained stable until at least 6 months post-ECT, independently of severity of WMH, GCA, or MTA. Therefore, clinicians should not be reluctant to start or continue ECT in patients with severe structural brain alterations.

Does lithium prevent relapse following successful electroconvulsive therapy for major depression? A systematic review and meta-analysis.

OBJECTIVE: The risk of relapse following successful antidepressant treatment, including electroconvulsive therapy (ECT), is substantial. Lithium has been suggested to effectively prevent relapse, yet data remain limited and inconclusive. We performed a systematic review and meta-analysis to examine the efficacy of continuation treatment with lithium in preventing relapse following a successful acute course of ECT in patients with major depression, in comparison to continuation treatment without lithium. We also assessed the role of several study characteristics, possibly impacting the treatment effect. METHODS: A systematic literature search, using the PubMed, Embase, Web of Science, and Cochrane Library databases (up to June 2020), was conducted for prospective and retrospective studies, including patients with unipolar or bipolar depression, that assessed the efficacy of lithium for post-ECT depressive relapse prevention. RESULTS: Of 2556 records screened, 14 articles reporting on 9748 participants who received continuation treatment either with (N = 1571) or without lithium (N = 8177) were included in the meta-analysis. Patients receiving lithium were less likely to experience depressive relapse after a successful acute course of ECT, compared to patients receiving post-ECT prophylaxis without lithium (weighted odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.34, 0.82), with a number needed to treat (NNT) of 7 (95% CI = 4, 21). We found some limited evidence that older patients may benefit more from continuation treatment with lithium, compared to younger patients. Using the GRADE criteria, the quality of evidence for our outcome measure (i.e., relapse rate) was rated as very low. CONCLUSION: Continuation treatment with lithium may have superior efficacy in reducing the risk of relapse after a successful acute ECT course for major depression, in comparison to continuation treatment without lithium. High-quality studies are needed to confirm this finding.

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

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

Relapse after abrupt discontinuation of maintenance electroconvulsive therapy during the COVID-19 pandemic.

OBJECTIVE: Maintenance electroconvulsive therapy (M-ECT) is considered an effective relapse prevention strategy in severe mood and psychotic disorders. How long M-ECT should be continued, and what the outcome is after its discontinuation has not been adequately studied. In our tertiary psychiatric hospital, M-ECT treatments were suspended at the start of the COVID-19 pandemic. We aimed to determine the 6-month relapse rate and time to relapse after abrupt discontinuation of M-ECT and to assess the impact of patient and treatment characteristics on the risk of relapse. METHODS: Eighty-one patients whose M-ECT was discontinued abruptly were followed up prospectively for 6 months, or until relapse (i.e., hospital admission, restart of ECT, change of pharmacotherapy, or suicide (attempt)). We used multivariable Cox proportional hazards models to assess the impact of patient and treatment characteristics on the risk of relapse. RESULTS: Thirty-six patients (44.44%) relapsed within 6 months following abrupt discontinuation of M-ECT. A greater number of previous acute ECT courses, a diagnosis of psychotic disorder (compared with major depressive disorder or bipolar disorder), and a shorter interval between M-ECT treatments at the time of discontinuation were significantly associated with increased risk of relapse. CONCLUSION: Almost half of the patients relapsed, similar to the relapse rate after a successful acute course of ECT. Patients with a shorter interval between M-ECT treatments at the time of discontinuation seem to be at increased risk, as well as patients with a diagnosis of psychotic disorder, compared to patients with mood disorders.

Inflammatory Markers May Inform the Effects of Electroconvulsive Therapy on Cognition in Patients with Depression.

INTRODUCTION: The neurobiological mechanisms underlying the acute cognitive effects of electroconvulsive therapy (ECT) remain poorly understood. Prior research has shown that proinflammatory cytokines such as IL-6, TNF-α, IL1-ß, and IL-10 may interfere with cognitive functioning. Interestingly, immunomodulation is one of the proposed modes of action of ECT. This study investigates whether changes of peripheral levels of IL-6, TNF-α, IL1-ß, and IL-10 are related to changes in cognitive functioning following ECT. METHODS: In the week before and 1 week after an acute course of ECT, 62 patients suffering from depression underwent a neuropsychological evaluation to assess their processing speed using the Symbol Digit Substitution Test (SDST), verbal episodic memory using the Hopkins Verbal Learning Test-Revised (HVLT-R), and their retrospective autobiographic memory using the Autobiographical Memory Interview (AMI) with the peripheral inflammatory markers being measured at the same 2 time points. RESULTS: Patients improved drastically following ECT, while their main performance on both the HVLT-R and AMI declined and their SDST scores remained stable. The levels of IL-6 and IL1-ß had both decreased, where the decrease in IL-6 was related to the decrease in HVLT-R scores. Higher baseline IL-10 levels were associated with a more limited decrease of the HVLT-R scores. CONCLUSION: Our findings tentatively suggest that the effects of ECT on verbal episodic memory may be related to the treatment's immunomodulatory properties, most notably due to decreased IL-6 levels. Moreover, baseline IL-10 appears to be a potential biomarker to predict the effects of ECT on verbal episodic memory. Whilst compelling, the results of this study should be interpreted with caution as, due to its exploratory nature, no correction for multiple comparisons was made. Further, a replication in larger cohorts is warranted.