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... Show moreObjective: 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. Show less
Hebbrecht, K.; Giltay, E.J.; Birkenhager, T.K.; Sabbe, B.; Verwijk, E.; Obbels, J.; ... ; Diermen, L. van 2020
Objective The Montreal Cognitive Assessment (MoCA) is a sensitive and clinically practical test but its usefulness in measuring long-term cognitive effects of ECT is unclear. Using the MoCA, we... Show moreObjective The Montreal Cognitive Assessment (MoCA) is a sensitive and clinically practical test but its usefulness in measuring long-term cognitive effects of ECT is unclear. Using the MoCA, we investigated short- and long-term global cognitive change in ECT-treated patients with a Major Depressive Episode (MDE). Method We included 65 consecutive ECT-treated patients with MDE, in whom global cognitive functioning was assessed at baseline (T0); during ECT (before the third session; T1); and 1 week (T2), 3 months (T3), and 6 months (T4) after completion of the index course. Changes in MoCA (sub)scores were analyzed using linear mixed models and reliable change indices were computed to investigate individual changes in MoCA total scores. Results There was a significant effect of time on MoCA scores (F(4, 230.5) = 4.14,P = 0.003), with an improvement in global cognitive functioning from T3 compared to T1 and T2. At the individual level, 26% (n = 17) of patients showed a significantly worse cognitive functioning at T2 and 12% (n = 8) an improved cognitive functioning compared to T0. For T4, these percentages ameliorated to 8% and 18% respectively. Conclusion No persistent global cognitive impairment induced by ECT was found at the group level using the MoCA. At the individual level, however, there was clear heterogeneity in the effects of ECT on cognitive functioning. The MoCA is a suitable tool to monitor short- and long-term global cognitive functioning in ECT-treated patients with MDE but in younger patients, potential ceiling effects must be taken into account. Show less
Baeten, R.F.; Rossum, E.F.C. van; Rijke, Y.B. de; Sabbe, B.G.C.; Mast, R.C. van der; Belge, J.B.; ... ; Diermen, L. van 2020
Background: There is substantial evidence showing changes in hypothalamic pituitary adrenal (HPA)-axis ac-tivity in patients with major depressive disorder (MDD). Also, there seem to be differences... Show moreBackground: There is substantial evidence showing changes in hypothalamic pituitary adrenal (HPA)-axis ac-tivity in patients with major depressive disorder (MDD). Also, there seem to be differences in HPA-axis func-tioning between MDD subgroups. It is however unclear whether hair cortisol concentrations (HCC), which are a stable marker of long-term cortisol levels, are suitable as a biomarker for identifying subgroups in MDD. Methods: We were able to attain valid HCC from a scalp hair sample of sixty-two patients with a major de-pressive episode right before electroconvulsive therapy (ECT). HCC were our main biological outcome measure. We created subgroups using depression severity as defined by the Hamilton Depression Rating Scale, the pre-sence/absence of psychotic symptoms, the presence of melancholia as defined by the CORE and catatonia as defined by the Bush-Francis Catatonia Rating Scale. Results: Our analyses of the total group showed a median HCC of 4.4 pg/mg. We found patients with catatonia (N = 10) to have substantially higher median HCC (8.3 pg/mg) than patients without catatonia (3.8 pg/mg). Although presence of melancholia and depression severity were not significantly associated with HCC, more severe psychomotor agitation was associated with higher HCC. Pre-treatment HCC was not associated with ECT outcome. Strengths and limitations: A complicating factor in interpretation of our results was the large variability in HCC. This could be related to potential confounders such as cardiometabolic and other comorbidities, that were however addressed to the extent possible. Conclusions: HCC is a potential biomarker for MDD patients with severe agitation and/or catatonia. ClinicalTrials.gov: Identifier: NCT02562846. Show less
Vermeulen, T.; Lauwers, T.; Diermen, L. van; Sabbe, B.G.; Mast, R.C. van der; Giltay, E.J. 2019
A major depressive disorder with psychotic features, that is, psychotic depression (PD), is often accompanied by cognitive deficits, particularly in older patients. We aimed to assess to what... Show moreA major depressive disorder with psychotic features, that is, psychotic depression (PD), is often accompanied by cognitive deficits, particularly in older patients. We aimed to assess to what extent various cognitive domains are affected in older patients with PD compared to those with nonpsychotic depression (NPD). Therefore, a systematic search was conducted in Medline, Embase, Web of Science, the Cumulative Index to Nursing and Allied Literature CINAHL), Google Scholar, and Cochrane for all relevant studies. Hereafter, we conducted a meta-analysis of seven studies on cognitive deficits in older adults 55+ years), comparing patients with PD and patients with NPD. Compared to patients with NPD, those with PD not only showed a significantly poorer perfor- mance on overall cognitive function, with a Hedges' g effect size of -0.34 95% confidence interval: -0.56; -0.12; p = 0.003), but also on nearly all sepa- rate cognitive domains, with Hedges' g effect sizes ranging from -0.26 to -0.64 (all p's <0.003), of which attention was most adversely affected. Verbal fluency showed no significant effect, although this analysis may have been underpowered. The funnel plot suggested no significant publication bias (Egger test intercept: -2.47; 95% confidence interval: -5.50; 0.55; p = 0.09). We conclude that older patients with PD show more cognitive deficits on all cognitive domains, except for verbal fluency, compared to patients with NPD. It is crucial that clinicians and researchers take cognitive deficits into consideration in older adults with PD. Show less
Diermen, L. van; Versyck, P.; Ameele, S. van den; Madani, Y.; Vermeulen, T.; Fransen, E.; ... ; Schrijvers, D. 2019
Objectives The presence of psychotic symptoms is an important predictor of responsiveness to electroconvulsive therapy (ECT). This study investigates whether a continuous severity measure, the... Show moreObjectives The presence of psychotic symptoms is an important predictor of responsiveness to electroconvulsive therapy (ECT). This study investigates whether a continuous severity measure, the Psychotic Depression Assessment Scale (PDAS), is a more accurate predictor. Methods Depression severity was assessed before and after the ECT course using the Montgomery-Asberg Depression Rating Scale (MADRS) in 31 patients with psychotic depression and 34 depressed patients without psychotic symptoms. Logistic regression models for MADRS response and remission were fitted, with either the PDAS total score or the dichotomous predictors "absence/presence of psychotic symptoms" as the independent variables. Age, episode duration, and treatment resistance were added as covariates. Results Both the asserted presence of psychotic symptoms and a higher PDAS total score reflected MADRS response (areas under the curve, 0.83 and 0.85, respectively), with MADRS remission also being predicted by the presence of psychotic symptoms and higher PDAS scores (areas under the curves, 0.86 and 0.84, respectively). Age was a contributor to these prediction models, with response and remission rates being highest in the older patients. Psychotic Depression Assessment Scale scores decreased significantly during ECT: at end point, 81.5% of the patients showed significant response and 63.9% had achieved remission. Conclusions The PDAS indeed accurately predicts response to and remission after ECT in (psychotic) depression and most pronouncedly so in older patients but seems to have no clear advantage over simply verifying the presence of psychotic symptoms. This could be the consequence of a ceiling effect, as ECT was extremely effective in patients with psychotic depression. ClinicalTrials.gov: Identifier: NCT02562846. Show less
Diermen, L. van; Vanmarcke, S.; Walther, S.; Moens, H.; Veltman, E.; Fransen, E.; ... ; Schrijvers, D. 2019
Psychomotor symptoms are core features of melancholic depression. This study investigates whether psychomotor disturbance predicts the outcome of electroconvulsive therapy (ECT) and how the... Show morePsychomotor 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. Show less
