NCT05768126

Prediction of ECT Treatment Response and Reduction of Cognitive Side-effects Using EEG and Rivastigmine

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: UMC Utrecht · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to test the beneficial effects of rivastigmine administration, and predict the treatment outcome with electroencephalography (EEG), in patients with severe depression treated with electroconvulsive therapy (ECT). The study has two main objectives: * to study whether rivastigmine would ameliorate the side-effect profile of ECT * to develop an outcome prediction model based on resting state EEG for both the response to treatment as well as its side effect Participants will be assessed by: * Cognitive tests * Questionnaires of clinical symptoms * Questionnaires of depressive symptoms * Bloodsample * Resting state and task-based EEG Researchers will compare patients with a depressive disorder treated with ECT receiving rivastigmine to placebo patches to see if rivastigmine reduces cognitive side effects.

Detailed description

Electroconvulsive therapy (ECT) is the most potent psychiatric treatment, with an effect size of 1.5 for severe and refractory unipolar and bipolar depression. ECT convincingly outperforms pharmacotherapy such as tricyclic antidepressants and monoamine oxidase inhibitors and any form of psychotherapy. Despite its outstanding performance in reducing depressive symptoms up to the point of full remission, it is used only marginally. One reason for its infrequent use may be that the response to ECT is largely unpredictable, while cognitive side-effects occur frequently. In a previous study, the researchers found that multiple cognitive tests showed a significant decline immediately post-ECT, which resolved within 6 months after the last ECT session without further treatment. Even though cognitive side-effects are mostly short-lasting, both patients and doctors see this as a great drawback of ECT. If these disturbing side-effects could be prevented, more patients and psychiatrists would choose ECT as a treatment option. This would lead to a more effective treatment and hence shorter duration of chronic severe depression and improvement in quality of life, while costs for health care and loss of productivity would decrease. A potential way of ameliorating side effects, could be to add a cholinesterase inhibitor to ECT treatment. Rodent studies show that the loss of cholinergic fibers specifically correlated to the cognitive side effects of rodents after electroconvulsive stimulation (ECS). The researchers selected rivastigmine (a cholinesterase inhibitor) as a potential candidate in counteracting cognitive side effects induced by cholinergic fiber loss due to ECT. Rivastigmine patches are very well tolerated and widely used for Alzheimer's and Parkinson's dementia. Tailoring treatment to patients that are likely to respond while cognitive side-effects are unlikely to occur, would be another important improvement for depressed patients. Currently, ECT outcome is unpredictable. Factors that favor response include older age, psychotic depression, shorter duration of the depressive episode, and smaller volumes of the dentate gyrus (a part of the hippocampus). However, these predictors do not provide enough accuracy to make individual response profiles. Accurately classifying specifically non-responders will prevent application of ineffective treatment with potential iatrogenic damage, while more accurately predicted response will increase the applicability of ECT as treatment option. A potentially powerful way that is easy to implement in the clinic is prediction of ECT response using resting state EEG characteristics in addition to clinical information.

Conditions

• Depressive Disorder

Interventions

Type	Name	Description
DRUG	Rivastigmine Transdermal Product	The patches will be administered (first four weeks 4.6 mg and then 9.5. mg).
OTHER	Sham	The sham patches will be administered during the same period of time as the rivastigmine.

Timeline

• Start date: 2021-09-29
• Primary completion: 2025-12-01
• Completion: 2026-01-01
• First posted: 2023-03-14
• Last updated: 2024-05-10

Locations

1 site across 1 country: Netherlands