Minder hinder na een epileptische aanval

Rationale: Postictal phenomena, such as sensory, motor or memory deficits, headache, delirium, and psychosis, are common manifestations after epileptic and electroconvulsive therapy (ECT) induced seizures and add to the burden of disease. The pathophysiology of these phenomena is poorly understood and specific treatments are not available. Recently, seizure-induced postictal vasoconstriction with hypoperfusion was observed in experimentally induced seizures in rats. Treatment with acetaminophen or calcium antagonists decreased hypoperfusion and postictal phenomena.

Objective: To study the influence of acetaminophen and nimodipine on postictal phenomena after ECT induced seizures.

Study design: A prospective, three conditions cross-over trial, with randomized condition allocation, open-label, and blinded end-point evaluation (PROBE design).

Study population: Thirty-three adult (age >17 years) patients referred to treatment with ECT for a depressive episode will be included.

Intervention: A single dose of nimodipine (60 mg) or acetaminophen (1000 mg) or no additional treatment will be given prior to each ECT-session. Patients will be randomly assigned to predefined treatment sequences.
Main study parameters/endpoints: The primary outcome measure is the duration of the postictal phase as measured electrographically and expressed as ‘time to EEG normalization’. Secondary outcome measures include clinical ‘time to orientation’ and postictal cerebral perfusion as measured by perfusion weighted MRI.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Acetaminophen (Paracetamol) is a widely used analgesic drug. A single dose of 1000mg has no relevant side effects. Nimodipine in a dose of 60mg, 6 times daily during three weeks, is part of standard treatment for prevention of vasoconstriction in patients with subarachnoid haemorrhage and generally well tolerated. A single dose of 60mg may in a few cases cause a temporary reduction in blood pressure. Since this treatment is administered in the highly-controlled environment of an operation theatre, where ECT takes place, we consider this associated risk as negligible. MRI scanning and cognitive evaluation shortly after the ECT-session may be perceived as inconvenient by some patients, but we foresee no relevant additional risks. Important possible benefits include a reduction of postictal symptoms with acetaminophen or nimodipine treatment in the future.

We hypothesize that acetaminophen and nimodipine have a positive influence on postictal phenomena after ECT induced seizures and this is mediated by a reduction of postictal cerebral hypoperfusion.

Baseline: next to standard structural MRI and EEG, the additional MRI scans will be performed, as well as the psychological inventory.

After each ECT-session: reorientation time (ROT) and VAS-scores of myalgia, headache and nausea.

After three of the ECT-sessions: MRI-scans (see secondary outcomes) within 1 hour of ECT.

End of ECT-course: psychological inventory.

3 months after ECT-course: psychological inventory next to common practice EEG and MRI.

A single dose of nimodipine (60 mg) or acetaminophen (1000 mg) or no additional treatment will be given prior to each ECT-session. Patients will be randomly assigned to predefined treatment sequences.