Depression, Electroconvulsive Therapy, Epilepsy, Postictal Delirium
Conditions
Keywords
Epilepsy, Depression, Electroconvulsive Therapy, Postictal, Clinical Trial, Postictal hypoperfusion/hypoxia
Brief summary
In this clinical trial, postictal phenomena (i.e., headache, delirium) will be investigated after administration of acetaminophen and nimodipine in depressed patients receiving electroconvulsive therapy (ECT). Postictal phenomena are thought to result from decreased cerebral blood flow and decreased oxygen concentration in the brain. It is expected that acetaminophen and nimodipine will reduce these postictal phenomena, compared to no treatment, because they target these mechanisms.
Detailed description
Postictal phenomena, such as sensory, motor or memory deficits, headache, delirium, and psychosis, are common manifestations after electroconvulsive therapy (ECT) induced seizures. Also, postictal phenomena add to the burden of seizures in patients with epilepsy. The pathophysiology of these phenomena is poorly understood and effective treatments are not available (Fisher RS, 2000; Krauss & Theodore, 2010). Recently, seizure-induced postictal vasoconstriction with cerebral hypoperfusion was observed in experimentally induced seizures in rats. Treatment with acetaminophen or calcium antagonists decreased hypoperfusion and postictal phenomena (Farrell, 2016, 2017). The objective of this research is to study the effect of acetaminophen and nimodipine to reduce postictal phenomena after ECT induced seizures. A prospective, three conditions crossover trial will be conducted, with randomized condition allocation, open-label treatment, and blinded end-point evaluation (PROBE design; Hansson, Hedner, & Dahlof, 1992). Thirty-three adult (age \>17 years) patients referred to treatment with ECT for a depressive episode will be included to achieve a statistical power of .80. This will be feasible in one year. A single dose of nimodipine (60 mg) or acetaminophen (1000 mg) or no additional treatment will be given prior to a maximum of 12 ECT-sessions per patient. Patients will be randomly assigned to predefined treatment sequences. EEG and MRI measures will serve as main outcome measures, as well as psychometric tests. Data will be stored on two separate hard disks, one including patient sensitive information for identification, the other with anonymized data only (for the sponsor). Patients will be recruited by doctors at Rijnstate Hospital Arnhem. A mixed model with repeated measurements analysis will be conducted for the primary outcome measures.
Interventions
DRUGParacetamol
once, 1000mg, 2 h before ECT session
DRUGNimotop
once, 60mg, 2 h before ECT session
Sponsors
University of Twente
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Rijnstate Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Masking description
The PROBE design will be used in this study, in which the principal investigator will be blinded to the administration of drugs until the end of the study. The other principal investigator will know about administration, but will not be involved in testing patients.
Intervention model description
This study makes use of a 3 x 3 crossover design, in which patients receive a randomized sequence of interventions in pairs of 3 (acetaminophen, nimodipine, no intervention), with a maximum of 12 interventions/measurements.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adulthood (age \> 17 years); * Current clinical diagnosis of depressive episode (unipolar, bipolar, schizoaffective); * Willingness and ability to give written informed consent and willingness and ability to understand, to participate and to comply with the study requirements.
Exclusion criteria
* Known adverse or allergic reactions to acetaminophen or nimodipine; * Chronic use of acetaminophen, calcium-antagonists or NSAID's that cannot be interrupted for less than two days before the ECT-session;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to EEG normalization | Change from ictal to baseline EEG activity, up to 12 times per patient (across 6 weeks) | quantitative metric of EEG background evolution over time, in seconds (will be assessed at baseline, during electroconvulsive therapy, and immediately afterwards for approximately 1 hour) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postictal reorientation time (by Sobin, 1995) | immediately after each ECT session, up to 12 times per patient (across 6 weeks) | Five questions regarding reorientation will be asked in an interval of 5 minutes after electroconvulsive shock therapy has ended. If the patient can answer 4 out of the 5 questions correctly, this is determined as the final score (in minutes). The scale ranges from 5 to 100 minutes. These scores indicate the time frame a patient needs until he/she is fully conscious and reoriented. Higher values indicate that a patient needs more time to regain reorientation. |
| Structural MRI | baseline, in the first hour after 3 electroconvulsive therapy sessions, after approx. 3 months, after approx. 6 months, lasts approx. 5 min. | Isovoxel T1-weighted data (to make volumetric changes); is part of the MRI sequence (takes in total approximately 25 minutes) |
| Arterial Spin Labeling MRI | baseline, in the first hour after 3 electroconvulsive therapy sessions, after approx. 3 months, after approx. 6 months, lasts approx. 7 min. | measures cerebral perfusion levels |
| Resting state functional MRI | baseline, in the first hour after 3 electroconvulsive therapy sessions, after approx. 3 months, after approx. 6 months, lasts approx. 5 min. | used for brain mapping, measures functional organization (and connectivity) of certain brain areas |
| Diffusion Tensor Imaging | baseline, in the first hour after 3 electroconvulsive therapy sessions, after approx. 3 months, after approx. 6 months, lasts approx. 5 min. | measures diffusion in the brain to estimate the axonal organization of the brain |
Countries
Netherlands
Outcome results
None listed