TY - JOUR
T1 - Study of effect of nimodipine and acetaminophen on postictal symptoms in depressed patients after electroconvulsive therapy (SYNAPSE)
AU - Verdijk, Joey P.A.J.
AU - Pottkämper, Julia C.M.
AU - Verwijk, Esmée
AU - van Wingen, Guido A.
AU - van Putten, Michel J.A.M.
AU - Hofmeijer, Jeannette
AU - van Waarde, Jeroen A.
N1 - Funding Information:
We thank all involved colleagues at Rijnstate hospital for the help and flexibility in this logistically complicated trial. Aside from the main contributing departments of Neurology and Psychiatry, special thanks go to the departments of Radiology and Anesthesiology. We also would like to thank Oscar Buno Heslinga BSc (research nurse), Sven Stuiver MSc and Eva Albrecht MSc (research assistants), and Arnoud and Marleen (volunteers) for coordinating patients, help with transfers, and their assistance in the neuropsychological assessments. MvP, JH, and JvW devised the main conceptual ideas and proof outline. JV wrote the study protocol with the help of MvP, JH, JvW, and JP. All authors revised the protocol. JP will perform EEG data acquisition and analyses. JV will perform analysis of secondary research questions. EV supervises neuropsychological testing. GvW supervises neuroimaging analyses. All authors read and approved the final manuscript. All psychiatrists of Rijnstate, including JvW, will treat the patients with ECT. JV is medical doctor and resident in psychiatry in Rijnstate Hospital, Arnhem, and PhD candidate at University of Twente, Enschede, The Netherlands. JP is PhD candidate at University of Twente, Enschede, The Netherlands. EV is clinical neuropsychologist at the Amsterdam University Medical Centres and assistant-professor at the University of Amsterdam, Amsterdam, The Netherlands. GvW is professor of Neuroimaging in psychiatry at Amsterdam University Medical Centres and the University of Amsterdam, Amsterdam, The Netherlands. MvP is neurologist in Medisch Spectrum Twente, Enschede, and professor of Clinical Neurophysiology at the Institute of Technical Medicine, University of Twente, Enschede, The Netherlands. JH is neurologist in Rijnstate Hospital and professor of Translational Neurophysiology at the Institute of Technical Medicine, University of Twente, Enschede, The Netherlands. JvW is principal investigator, psychiatrist and director of residence training in psychiatry at Rijnstate Hospital, Arnhem, The Netherlands. This study was funded by the Dutch Epilepsy Foundation. The funding party has no role in study management, analysis, interpretation of data, writing, and submission. The research group is independent from funding in the execution of the trial and has ultimate authority over all these activities. The datasets used and/or analysed during the current study will be available from the corresponding author on reasonable request.
Funding Information:
This study was funded by the Dutch Epilepsy Foundation. The funding party has no role in study management, analysis, interpretation of data, writing, and submission. The research group is independent from funding in the execution of the trial and has ultimate authority over all these activities.
Publisher Copyright:
© 2022, The Author(s).
Financial transaction number:
2500002804
PY - 2022/12
Y1 - 2022/12
N2 - Background: Postictal phenomena as delirium, headache, nausea, myalgia, and anterograde and retrograde amnesia are common manifestations after seizures induced by electroconvulsive therapy (ECT). Comparable postictal phenomena also contribute to the burden of patients with epilepsy. The pathophysiology of postictal phenomena is poorly understood and effective treatments are not available. Recently, seizure-induced cyclooxygenase (COX)-mediated postictal vasoconstriction, accompanied by cerebral hypoperfusion and hypoxia, has been identified as a candidate mechanism in experimentally induced seizures in rats. Vasodilatory treatment with acetaminophen or calcium antagonists reduced postictal hypoxia and postictal symptoms. The aim of this clinical trial is to study the effects of acetaminophen and nimodipine on postictal phenomena after ECT-induced seizures in patients suffering major depressive disorder. We hypothesize that (1) acetaminophen and nimodipine will reduce postictal electroencephalographic (EEG) phenomena, (2) acetaminophen and nimodipine will reduce magnetic resonance imaging (MRI) measures of postictal cerebral hypoperfusion, (3) acetaminophen and nimodipine will reduce clinical postictal phenomena, and (4) postictal phenomena will correlate with measures of postictal hypoperfusion. Methods: We propose a prospective, three-condition cross-over design trial with randomized condition allocation, open-label treatment, and blinded end-point evaluation (PROBE design). Thirty-three patients (age > 17 years) suffering from a depressive episode treated with ECT will be included. Randomly and alternately, single doses of nimodipine (60 mg), acetaminophen (1000 mg), or water will be given two hours prior to each ECT session with a maximum of twelve sessions per patient. The primary outcome measure is ‘postictal EEG recovery time’, expressed and quantified as an adapted version of the temporal brain symmetry index, yielding a time constant for the duration of the postictal state on EEG. Secondary outcome measures include postictal cerebral perfusion, measured by arterial spin labelling MRI, and the postictal clinical ‘time to orientation’. Discussion: With this clinical trial, we will systematically study postictal EEG, MRI and clinical phenomena after ECT-induced seizures and will test the effects of vasodilatory treatment intending to reduce postictal symptoms. If an effect is established, this will provide a novel treatment of postictal symptoms in ECT patients. Ultimately, these findings may be generalized to patients with epilepsy. Trial registration: Inclusion in SYNAPSE started in December 2019. Prospective trial registration number is NCT04028596 on the international clinical trial register on July 22, 2019.
AB - Background: Postictal phenomena as delirium, headache, nausea, myalgia, and anterograde and retrograde amnesia are common manifestations after seizures induced by electroconvulsive therapy (ECT). Comparable postictal phenomena also contribute to the burden of patients with epilepsy. The pathophysiology of postictal phenomena is poorly understood and effective treatments are not available. Recently, seizure-induced cyclooxygenase (COX)-mediated postictal vasoconstriction, accompanied by cerebral hypoperfusion and hypoxia, has been identified as a candidate mechanism in experimentally induced seizures in rats. Vasodilatory treatment with acetaminophen or calcium antagonists reduced postictal hypoxia and postictal symptoms. The aim of this clinical trial is to study the effects of acetaminophen and nimodipine on postictal phenomena after ECT-induced seizures in patients suffering major depressive disorder. We hypothesize that (1) acetaminophen and nimodipine will reduce postictal electroencephalographic (EEG) phenomena, (2) acetaminophen and nimodipine will reduce magnetic resonance imaging (MRI) measures of postictal cerebral hypoperfusion, (3) acetaminophen and nimodipine will reduce clinical postictal phenomena, and (4) postictal phenomena will correlate with measures of postictal hypoperfusion. Methods: We propose a prospective, three-condition cross-over design trial with randomized condition allocation, open-label treatment, and blinded end-point evaluation (PROBE design). Thirty-three patients (age > 17 years) suffering from a depressive episode treated with ECT will be included. Randomly and alternately, single doses of nimodipine (60 mg), acetaminophen (1000 mg), or water will be given two hours prior to each ECT session with a maximum of twelve sessions per patient. The primary outcome measure is ‘postictal EEG recovery time’, expressed and quantified as an adapted version of the temporal brain symmetry index, yielding a time constant for the duration of the postictal state on EEG. Secondary outcome measures include postictal cerebral perfusion, measured by arterial spin labelling MRI, and the postictal clinical ‘time to orientation’. Discussion: With this clinical trial, we will systematically study postictal EEG, MRI and clinical phenomena after ECT-induced seizures and will test the effects of vasodilatory treatment intending to reduce postictal symptoms. If an effect is established, this will provide a novel treatment of postictal symptoms in ECT patients. Ultimately, these findings may be generalized to patients with epilepsy. Trial registration: Inclusion in SYNAPSE started in December 2019. Prospective trial registration number is NCT04028596 on the international clinical trial register on July 22, 2019.
KW - Acetaminophen
KW - Arterial spin labelling (or perfusion weighted imaging)
KW - Cerebral perfusion
KW - Depression
KW - Electroconvulsive therapy
KW - Electroencephalography
KW - Epilepsy
KW - Nimodipine
KW - Postictal
KW - PROBE design
UR - http://www.scopus.com/inward/record.url?scp=85128544516&partnerID=8YFLogxK
U2 - 10.1186/s13063-022-06206-y
DO - 10.1186/s13063-022-06206-y
M3 - Article
C2 - 35436940
AN - SCOPUS:85128544516
SN - 1745-6215
VL - 23
JO - Trials
JF - Trials
IS - 1
M1 - 324
ER -