flumazenil and Recrudescence studies

Flumazenil: A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses.
flumazenil : An organic heterotricyclic compound that is 5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine which is substituted at positions 3, 5, 6, and 8 by ethoxycarbonyl, methyl, oxo, and fluoro groups, respectively. It is used as an antidote to benzodiazepine overdose.

Research Excerpts

Excerpt	Relevance	Reference
"Three cases of seizure recurrence after flumazenil use in this context are reported, and the pharmacology is discussed."	5.33	Danger of flumazenil use in pediatric status epilepticus. ( Brierley, J, 2006)
"To assess the efficacy, usefulness, safety, and dosages of flumazenil required when flumazenil is used in the diagnosis of benzodiazepine-induced coma (vs."	5.08	Use of flumazenil in the treatment of drug overdose: a double-blind and open clinical study in 110 patients. ( Geller, E; Halpern, P; Nevo, Y; Niv, D; Rudick, V; Sorkine, P; Weinbroum, A, 1996)
" Idiopathic recurring stupor (IRS) is a syndrome of spontaneous stupor or coma that is not associated with known metabolic, toxic, or structural abnormalities but can be reversed by flumazenil, a pure benzodiazepine antagonist."	3.68	Endogenous benzodiazepine receptor ligands in idiopathic recurring stupor. ( Avoni, P; Cortelli, P; Guidotti, A; Lugaresi, E; Montagna, P; Plazzi, G; Rothstein, JD; Schoch, P; Tinuper, P, 1992)
" Recurrent apnea was reversed after administration of flumazenil, a specific antagonist of benzodiazepines."	3.68	The use of flumazenil in a neonate. ( Autret, E; Barbier, P; Bardol, J; Jonville, AP; Ramponi, N; Richard, P; Soyez, C, 1991)
"Total sleep deprivation is the classic variant of its clinical use."	2.44	Sleep deprivation therapy. ( Svestka, J, 2008)
"Flumazenil is a competitive inhibitor of the benzodiazepines that is available for reversal at the end of such a procedure or when too much sedation has been achieved."	2.40	Reversal of midazolam-induced laryngospasm with flumazenil. ( Davis, DP; Hamilton, RS; Webster, TH, 1998)
"Flumazenil pretreatment of elderly ECT patients with declining seizure quality and inadequate clinical response in the setting of repeated treatments may represent a novel strategy for managing such patients."	1.38	Flumazenil pretreatment in benzodiazepine-free patients: a novel method for managing declining ECT seizure quality. ( Azner, Y; Reti, IM; Schiavi, A; Torres, J; Vaidya, P; Yi, J, 2012)
"Stupor is defined as a deep sleep or behaviourally similar unresponsiveness from which the subject can be aroused only by vigorous repeated stimuli."	1.35	Idiopathic recurrent stupor mimicking status epilepticus. ( Agrawal, S; Asthana, V; Goel, D; Sharma, JP, 2008)
"Three cases of seizure recurrence after flumazenil use in this context are reported, and the pharmacology is discussed."	1.33	Danger of flumazenil use in pediatric status epilepticus. ( Brierley, J, 2006)

Research

Studies (20)

Authors

Clinical Trials (3)

Trial Overview

Trial Outcomes

Percent Days Abstinent

Percent Subjects Completely Abstinent

Timeframe	Studies, this research(%)	All Research%
pre-1990	1 (5.00)	18.7374
1990's	11 (55.00)	18.2507
2000's	6 (30.00)	29.6817
2010's	2 (10.00)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Asthana, V	1
Agrawal, S	1
Goel, D	1
Sharma, JP	1
Svestka, J	1
Schacht, JP	1
Randall, PK	1
Waid, LR	1
Baros, AM	1
Latham, PK	1
Wright, TM	1
Myrick, H	1
Anton, RF	1
Yi, J	1
Torres, J	1
Azner, Y	1
Vaidya, P	1
Schiavi, A	1
Reti, IM	1
Huberfeld, G	1
Dupont, S	1
Hazemann, P	1
Adam, C	1
Baulac, M	1
Pierrot-Deseilligny, C	1
Cortelli, P	3
Avallone, R	1
Baraldi, M	1
Zeneroli, ML	1
Mandrioli, J	1
Corsi, L	1
Riva, R	1
Tinuper, P	4
Lugaresi, E	4
Baruzzi, A	1
Montagna, P	4
Brierley, J	1
Weinbroum, A	1
Rudick, V	1
Sorkine, P	1
Nevo, Y	1
Halpern, P	1
Geller, E	1
Niv, D	1
Shimoe, Y	1
Fukutake, T	1
Nakai, R	1
Hirayama, K	1
Macdonald, GA	1
Frey, KA	1
Agranoff, BW	1
Minoshima, S	1
Koeppe, RA	1
Kuhl, DE	1
Shulkin, BL	1
Lucey, MR	1
Plazzi, G	2
Gallassi, R	2
Wang, TC	1
Markey, SP	1
Rothstein, JD	2
Roberge, RJ	1
Atchley, B	1
Ryan, K	1
Krenzelok, EP	1
Davis, DP	1
Hamilton, RS	1
Webster, TH	1
Palmieri, MG	1
Iani, C	1
Scalise, A	1
Desiato, MT	1
Loberti, M	1
Telera, S	1
Caramia, MD	1
D'Alessandro, G	1
Corso, G	1
Bottacchi, E	1
Avoni, P	2
Lugaresi, A	1
Schoch, P	2
Bonetti, EP	1
Sforza, E	1
Guidotti, A	1
Richard, P	1
Autret, E	1
Bardol, J	1
Soyez, C	1
Barbier, P	1
Jonville, AP	1
Ramponi, N	1
Torres Ramirez, C	1
Fernández Morales, E	1
Zuluaga Gómez, A	1
Gálvez Alcaraz, L	1
Del Rio Samper, S	1
de la Calle-Martin, O	1
Hernandez, M	1
Ordi, J	1
Casamitjana, N	1
Arostegui, JI	1
Caragol, I	1
Ferrando, M	1
Labrador, M	1
Rodriguez-Sanchez, JL	1
Espanol, T	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Double Blind Evaluation of Flumazenil and Gabapentin for the Treatment of Alcohol Withdrawal and Relapse Prevention[NCT00262639]	Phase 2/Phase 3	60 participants (Actual)	Interventional	2005-12-31	Completed
Neurocognitive and Neurobehavioral Mechanisms of Change Following Psychological[NCT03842670]		140 participants (Anticipated)	Interventional	2018-11-14	Active, not recruiting
Effect of Flumazenil on Hypoactive Delirium in the ICU: A Double-Blind, Placebo-Controlled Pilot Study[NCT02899156]	Phase 4	22 participants (Actual)	Interventional	2016-03-31	Terminated (stopped due to A planned interim analysis led to the trial being stopped early based on the observed size effect and power analysis.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Intervention	percent days (Mean)
Low CIWA Flumazenil/Gabapentin	70.8
Low CIWAar Placebo	86.1
High CIWAar Placebo	75.9
High CIWAar Flumazenil/Gabapentin	95.9

percent of subjects completely abstinent during the six week medication study study (NCT00262639)
Timeframe: 6 week trial

Average Duration of Study Infusion

Intervention	percent of participants (Number)
Low CIWA Flumazenil/Gabapentin	44
Low CIWAar Placebo	19
High CIWAar Placebo	33
High CIWAar Flumazenil/Gabapentin	71

average duration of time patient was randomized to each infusion up to 72 hours (NCT02899156)
Timeframe: up to 72 hours after the start of the infusion

Average Maximum Rate of Study Infusion

Intervention	hours (Mean)
Flumazenil Group	54.8
Placebo Group	58.2

average maximum rate (ml/hr) during the 72 hours after study infusion (NCT02899156)
Timeframe: up to 72 hours after the start of the infusion

Intensive Care Unit Length of Stay

Intervention	milliliters per hour (Mean)
Flumazenil Group	5
Placebo Group	5.2

length of time that the patient was admitted to an intensive care unit service during the hospital stay (NCT02899156)
Timeframe: duration of admission to the intensive care unit

Number of Delirium-free Days

Intervention	days (Mean)
Flumazenil Group	7.8
Placebo Group	7

Defined by the number of days in the 14-day period after randomization that the patient was alive and not delirious (i.e. CAM-ICU negative). Zero delirium-free days will be observed for patients that die within the 14-day period. (NCT02899156)
Timeframe: up to 14 days after randomization

Number of Mechanical Ventilator Free Days

Intervention	days (Median)
Flumazenil Group	12.7
Placebo Group	9.2

number of days within the first 28 days after enrollment that the patient was free from needing mechanical ventilation (NCT02899156)
Timeframe: up to 28 days after randomization

Number of Participants With Delirium Resolution

Intervention	days (Mean)
Flumazenil Group	23.6
Placebo Group	24.9

defined by the proportion of patients who were delirium free at 14 days after randomization (NCT02899156)
Timeframe: up to 14 days after randomization

Occurrence of Agitation Requiring Use of Rescue Sedatives While on Study Infusion

Intervention	Participants (Count of Participants)
Flumazenil Group	9
Placebo Group	7

number of times that a RASS score of + 2 to +4 occurred that did not resolve with decreasing study infusion (NCT02899156)
Timeframe: up to 72 hours after the start of the infusion

Article	Year
Sleep deprivation therapy. Neuro endocrinology letters, 2008, Volume: 29 Suppl 1 Topics: Antipsychotic Agents; Circadian Rhythm; Clinical Trials as Topic; Combined Modality Therapy; Depress	2008
Endozepines in recurrent stupor. Sleep medicine reviews, 2005, Volume: 9, Issue:6 Topics: Coma; Diazepam Binding Inhibitor; Electroencephalography; Flumazenil; Hepatic Encephalopathy; Humans	2005
Reversal of midazolam-induced laryngospasm with flumazenil. Annals of emergency medicine, 1998, Volume: 32, Issue:2 Topics: Anti-Anxiety Agents; Antidotes; Conscious Sedation; Electric Countershock; Flumazenil; GABA Modulato	1998

Article	Year
Neurocognitive performance, alcohol withdrawal, and effects of a combination of flumazenil and gabapentin in alcohol dependence. Alcoholism, clinical and experimental research, 2011, Volume: 35, Issue:11 Topics: Adult; Alcohol Drinking; Alcoholism; Amines; Cognition; Cyclohexanecarboxylic Acids; Drug Therapy, C	2011
Neurocognitive performance, alcohol withdrawal, and effects of a combination of flumazenil and gabapentin in alcohol dependence. Alcoholism, clinical and experimental research, 2011, Volume: 35, Issue:11 Topics: Adult; Alcohol Drinking; Alcoholism; Amines; Cognition; Cyclohexanecarboxylic Acids; Drug Therapy, C	2011
Neurocognitive performance, alcohol withdrawal, and effects of a combination of flumazenil and gabapentin in alcohol dependence. Alcoholism, clinical and experimental research, 2011, Volume: 35, Issue:11 Topics: Adult; Alcohol Drinking; Alcoholism; Amines; Cognition; Cyclohexanecarboxylic Acids; Drug Therapy, C	2011
Neurocognitive performance, alcohol withdrawal, and effects of a combination of flumazenil and gabapentin in alcohol dependence. Alcoholism, clinical and experimental research, 2011, Volume: 35, Issue:11 Topics: Adult; Alcohol Drinking; Alcoholism; Amines; Cognition; Cyclohexanecarboxylic Acids; Drug Therapy, C	2011
Use of flumazenil in the treatment of drug overdose: a double-blind and open clinical study in 110 patients. Critical care medicine, 1996, Volume: 24, Issue:2 Topics: Adult; Aged; Antidepressive Agents, Tricyclic; Antidotes; Barbiturates; Benzodiazepines; Coma; Diagn	1996

Article	Year
Idiopathic recurrent stupor mimicking status epilepticus. Singapore medical journal, 2008, Volume: 49, Issue:10 Topics: Diagnosis, Differential; Electroencephalography; Flumazenil; GABA Modulators; Humans; Male; Middle A	2008
Flumazenil pretreatment in benzodiazepine-free patients: a novel method for managing declining ECT seizure quality. The journal of ECT, 2012, Volume: 28, Issue:3 Topics: Aged; Aged, 80 and over; Benzodiazepines; Combined Modality Therapy; Depressive Disorder, Major; Dos	2012
[Recurrent idiopathic stupor in a patient: responsibility of exogenous or endogenous benzodiazepines?]. Revue neurologique, 2002, Volume: 158, Issue:8-9 Topics: Benzodiazepines; Coma; Flumazenil; GABA Modulators; Humans; Middle Aged; Recurrence	2002
Danger of flumazenil use in pediatric status epilepticus. Pediatric emergency care, 2006, Volume: 22, Issue:3 Topics: Benzodiazepines; Child, Preschool; Female; Flumazenil; Humans; Infant; Male; Recurrence; Respiratory	2006
[Recurring consciousness disturbance with elevation of endogenous benzodiazepine-like activity]. Rinsho shinkeigaku = Clinical neurology, 1996, Volume: 36, Issue:3 Topics: Benzodiazepines; Consciousness Disorders; Flumazenil; GABA Modulators; Humans; Male; Middle Aged; Re	1996
Cerebral benzodiazepine receptor binding in vivo in patients with recurrent hepatic encephalopathy. Hepatology (Baltimore, Md.), 1997, Volume: 26, Issue:2 Topics: Adult; Brain; Carbon Radioisotopes; Female; Flumazenil; Hepatic Encephalopathy; Humans; Male; Middle	1997
Endozepine stupor. Recurring stupor linked to endozepine-4 accumulation. Brain : a journal of neurology, 1998, Volume: 121 ( Pt 1) Topics: Adult; Aged; Carrier Proteins; Coma; Diazepam Binding Inhibitor; Electroencephalography; Female; Flu	1998
Two chlorzoxazone (Parafon forte) overdoses and coma in one patient: reversal with flumazenil. The American journal of emergency medicine, 1998, Volume: 16, Issue:4 Topics: Antidotes; Chlorzoxazone; Coma; Drug Overdose; Emergency Treatment; Flumazenil; GABA Modulators; Hum	1998
The effect of benzodiazepines and flumazenil on motor cortical excitability in the human brain. Brain research, 1999, Jan-09, Volume: 815, Issue:2 Topics: Adolescent; Adult; Benzodiazepines; Coma; Electromagnetic Fields; Evoked Potentials, Motor; Female;	1999
Could flumazenil reverse neurological deficits in acute cerebral ischemia? Italian journal of neurological sciences, 1999, Volume: 20, Issue:1 Topics: Acute Disease; Brain Ischemia; Carotid Artery Thrombosis; Carotid Artery, Internal; Cerebral Angiogr	1999
Idiopathic recurring stupor: a case with possible involvement of the gamma-aminobutyric acid (GABA)ergic system. Annals of neurology, 1992, Volume: 31, Issue:5 Topics: Benzodiazepines; Coma; Electroencephalography; Flumazenil; GABA-A Receptor Antagonists; gamma-Aminob	1992
Endogenous benzodiazepine receptor ligands in idiopathic recurring stupor. Lancet (London, England), 1992, Oct-24, Volume: 340, Issue:8826 Topics: Adult; Aged; Chromatography, High Pressure Liquid; Coma; Diazepam Binding Inhibitor; Electroencephal	1992
The use of flumazenil in a neonate. Journal of toxicology. Clinical toxicology, 1991, Volume: 29, Issue:1 Topics: Apnea; Benzodiazepines; Flumazenil; Humans; Infant, Newborn; Recurrence	1991
An epidemiological study of renal lithiasis in gypsies and others in Spain. The Journal of urology, 1984, Volume: 131, Issue:5 Topics: Adolescent; Adult; Aged; Child; Dairy Products; Diet; Ethnicity; Female; Humans; Kidney Calculi; Mal	1984
Familial CD8 deficiency due to a mutation in the CD8 alpha gene. The Journal of clinical investigation, 2001, Volume: 108, Issue:1 Topics: Adult; Amino Acid Substitution; Animals; Antibody Formation; Bacterial Infections; CD8 Antigens; Chl	2001

flumazenil and Recrudescence