Measuring Blood Flow in the Brain After Epileptic Activity
Measuring Blood Flow in the Brain After Epileptic Activity
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.
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.
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;

 -  Contraindications for magnetic resonance imaging (e.g. ferromagnetic implants,
 pacemakers, claustrophobia)