quetiapine-fumarate and Brain-Injuries--Traumatic

Quetiapine is an atypical antipsychotic commonly used in critical care. Cellular and animal models demonstrated its novel anti-inflammatory properties in traumatic brain injury (TBI). Our study aimed to assess the effect of quetiapine on outcomes in critically ill TBI patients. We hypothesize that quetiapine improves neurological outcomes.. The Multiparameter Intelligent Monitoring in Intensive Care database was queried, and all adult (age, ≥18 years) isolated TBI patients (extracranial Abbreviated Injury Scale, < 2) admitted to the intensive care unit for a period of >48 hours. Patients were stratified into quetiapine (+) and no-quetiapine (-) groups. Propensity score matching was performed (1:2 ratio). Outcome measures were intensive care unit length of stay, discharge Glasgow Coma Scale (GCS), and mortality. A subanalysis was performed for patients who underwent intracranial pressure (ICP) monitoring to ascertain the effect of quetiapine dose on ICP, and cerebral perfusion pressure (CPP). Survival curves and regression analyses were performed.. A matched cohort of (quetiapine, 116 vs. no-quetiapine, 232) patients was obtained. Mean ± SD age was 65 ± 21 years, median head Abbreviated Injury Scale was 3 (3-4), and median GCS was 10 (9-16). The median quetiapine dose given was 50 (25-125) mg. Patients who received quetiapine had lower mortality (17.2% vs. 27.6%; p = 0.03) and a higher median GCS at discharge (12 [11-14] vs. 11 [10-13]; p < 0.04) but no difference in intensive care unit length of stay (4.1 days vs. 4.7 days; p = 0.75) or discharge to skilled nursing facility (34.5% vs. 31.9%; p = 0.63). On subanalysis of patients who received quetiapine, 40% had ICP monitoring. Higher doses of quetiapine were independently associated with progressively lower ICP (β = -0.022 mm Hg/mg of quetiapine; p = 0.01) and higher CPP (β = 0.031 mm Hg/mg quetiapine; p = 0.01).. Quetiapine may decrease mortality and improve neurological outcomes in critically ill TBI patients. It has a dose-dependent effect to decrease ICP and increase CPP. Quetiapine may be a potential therapeutic modality in critically ill TBI patients, but further studies are required to explore these mechanisms.. Systematic Review, level III.

Topics: Adult; Aged; Aged, 80 and over; Brain Injuries, Traumatic; Cerebrovascular Circulation; Critical Illness; Female; Glasgow Coma Scale; Humans; Intensive Care Units; Intracranial Pressure; Length of Stay; Male; Massachusetts; Middle Aged; Monitoring, Physiologic; Neuroprotective Agents; Propensity Score; Quetiapine Fumarate; Retrospective Studies; Survival Analysis

Topics: Antipsychotic Agents; Brain Injuries, Traumatic; Critical Illness; Humans; Neuroprotective Agents; Quetiapine Fumarate

Topics: Antipsychotic Agents; Brain Injuries, Traumatic; Critical Illness; Humans; Neuroprotective Agents; Quetiapine Fumarate

Schizophrenia is a chronic psychotic disorder in which patients experience positive and negative symptoms for over six months. Schizophrenia is associated with early mortality, with 40% of this excess mortality due to suicide. This is a case of patient with schizophrenia who was treated with quetiapine after suffering a traumatic brain injury and recovered enough to be discharged to a rehabilitation unit. This case illustrates the neuroprotective effects of quetiapine in treating neurologic deficits in a patient who recently suffered a traumatic brain injury.. This is a case report of a patient with schizophrenia treated in the hospital setting. He was placed on quetiapine after suffering a traumatic brain injury due to a suicide attempt in which he shot himself with a nail gun.. The patient initially presented with neurologic deficits suggestive of traumatic brain injury (inattention, memory loss, muscle weakness) and psychosis from schizophrenia. He was treated with quetiapine and recovered enough to be discharged to a rehabilitation unit.. Quetiapine, a second-generation antipsychotic, has been shown to significantly decrease blood–brain barrier hyperpermeability by preserving tight junction integrity in small animal models. This anti-inflammatory effect may also help to preserve neurogenesis in patients with traumatic brain injury, as shown in this case. This case may help elucidate the nature of quetiapine’s neuroprotective effects in patients who have suffered traumatic brain injury and also highlights the need to further investigate other atypical antipsychotics and their potential neuroprotective role in treating traumatic brain injury.

Topics: Adult; Antipsychotic Agents; Brain Injuries, Traumatic; Humans; Male; Neuroprotective Agents; Quetiapine Fumarate; Schizophrenia; Suicide, Attempted

The integrity of the blood-brain barrier (BBB) is paramount in limiting vasogenic edema following traumatic brain injury (TBI). The purpose of this study was to ascertain if quetiapine, an atypical antipsychotic commonly used in trauma/critical care for delirium, protects the BBB and attenuates hyperpermeability in TBI.. The effect of quetiapine on hyperpermeability was examined through molecular modeling, cellular models in vitro and small animal models in vivo. Molecular docking was performed with AutoDock Vina to matrix metalloproteinase-9. Rat brain microvascular endothelial cells (BMECs) were pretreated with quetiapine (20 μM; 1 hour) followed by an inflammatory activator (20 μg/mL chitosan; 2 hours) and compared to controls. Immunofluorescence localization for tight junction proteins zonula occludens-1 and adherens junction protein β-catenin was performed. Human BMECs were grown as a monolayer and pretreated with quetiapine (20 μM; 1 hour) followed by chitosan (20 μg/mL; 2 hours), and transendothelial electrical resistance was measured. C57BL/6 mice (n = 5/group) underwent mild to moderate TBI (controlled cortical impactor) or sham craniotomy. The treatment group was given 10 mg/kg quetiapine intravenously 10 minutes after TBI. The difference in fluorescence intensity between intravascular and interstitium (ΔI) represented BBB hyperpermeability. A matrix metalloproteinase-9 activity assay was performed in brain tissue from animals in the experimental groups ex vivo.. In silico studies showed quetiapine thermodynamically favorable binding to MMP-9. Junctional localization of zonula occludens-1 and β-catenin showed retained integrity in quetiapine-treated cells as compared with the chitosan group in rat BMECs. Quetiapine attenuated monolayer permeability compared with chitosan group (p < 0.05) in human BMECs. In the animal studies, there was a significant decrease in BBB hyperpermeability and MMP-9 activity when compared between the TBI and TBI plus quetiapine groups (p < 0.05).. Quetiapine treatment may have novel anti-inflammatory properties to provide protection to the BBB by preserving tight junction integrity.. level IV.

Topics: Animals; Antipsychotic Agents; beta Catenin; Blood-Brain Barrier; Brain; Brain Injuries, Traumatic; Cells, Cultured; Chitosan; Computer Simulation; Disease Models, Animal; Electric Impedance; Endothelial Cells; Humans; Intravital Microscopy; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Microvessels; Models, Molecular; Permeability; Quetiapine Fumarate; Rats; Tight Junctions; Zonula Occludens-1 Protein

Topics: Animals; Antipsychotic Agents; Brain Injuries, Traumatic; Cognition; Drug Administration Schedule; Haloperidol; Hindlimb; Male; Maze Learning; Motor Activity; Quetiapine Fumarate; Random Allocation; Rats; Recovery of Function; Reflex; Spatial Memory