The impact of treatment resistance on outcome and course of electroconvulsive therapy in major depressive disorder.

INTRODUCTION: Major depressive disorder (MDD) is a common psychiatric disorder. Despite several treatment options, a subgroup of patients will not respond to the commonly used antidepressant treatments and thus express treatment resistance (TRD). TRD can be quantified with the Dutch Measure for Treatment Resistance in Depression (DM-TRD). Electroconvulsive therapy (ECT) is an effective treatment for MDD, also in TRD. Yet, the position of ECT as "treatment-of-last-resort" may decrease the likelihood of beneficial outcome. Our aim was to investigate the association between treatment resistance and outcome and course of ECT. METHODS: We performed a retrospective, multicenter cohort study with 440 patients of which data was retrieved from patient records as collected in the Dutch ECT Cohort database. Linear and logistic regression models were used to explore the association between level of treatment resistance and outcome of ECT. Median split was used to explore the differences between high and low level of TRD and course of treatment. RESULTS: A higher DM-TRD score was associated with significantly smaller reduction of depression symptoms (R2 = 0.160; ß = -2.968; p < 0.001) and lower chance of response (OR = 0.821 [95 CI: 0.760-0.888]; ß = -0.197; p < 0.001). Low level TRD patients underwent fewer ECT sessions (mean 13 ± 6 SD vs. 16 ± 7 SD; p < 0.001) and fewer switches from right unilateral tot bifrontotemporal electrode placement (29% vs. 40%; p = 0.032). CONCLUSION: Reserving ECT as "treatment-of-last-resort" in the treatment algorithm for MDD seems questionable, because in our study lower level of treatment resistance predicted more beneficial ECT-outcome. Moreover, providing ECT in less treatment resistant patients showed fewer needed ECT-sessions and less switches to BL electrode placement, which may decrease the risk for cognitive side-effects.

Multimodal multi-center analysis of electroconvulsive therapy effects in depression: Brainwide gray matter increase without functional changes.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for severe depression and induces gray matter (GM) increases in the brain. Small-scale studies suggest that ECT also leads to changes in brain functioning, but findings are inconsistent. In this study, we investigated the influence of ECT on changes in both brain structure and function and their relation to clinical improvement using multicenter neuroimaging data from the Global ECT-MRI Research Collaboration (GEMRIC). METHODS: We analyzed T1-weighted structural magnetic resonance imaging (MRI) and functional resting-state MRI data of 88 individuals (49 male) with depressive episodes before and within one week after ECT. We performed voxel-based morphometry on the structural data and calculated fractional amplitudes of low-frequency fluctuations, regional homogeneity, degree centrality, functional connectomics, and hippocampus connectivity for the functional data in both unimodal and multimodal analyses. Longitudinal effects in the ECT group were compared to repeated measures of healthy controls (n = 27). RESULTS: Wide-spread increases in GM volume were found in patients following ECT. In contrast, no changes in any of the functional measures were observed, and there were no significant differences in structural or functional changes between ECT responders and non-responders. Multimodal analysis revealed that volume increases in the striatum, supplementary motor area and fusiform gyrus were associated with local changes in brain function. CONCLUSION: These results confirm wide-spread increases in GM volume, but suggest that this is not accompanied by functional changes or associated with clinical response. Instead, focal changes in brain function appear related to individual differences in brain volume increases.