title: Pharmacological interventions for agitation in patients with traumatic brain injury: protocol for a systematic review and meta-analysis.
abstract: Traumatic brain injury (TBI) is a worldwide leading cause of mortality and disability. Among TBI complications, agitation is a frequent behavioural problem. Agitation causes potential harm to patients and caregivers, interferes with treatments, leads to unnecessary chemical and physical restraints, increases hospital length of stay, delays rehabilitation, and impedes functional independence. Pharmacological treatments are often considered for agitation management following TBI. Several types of agents have been proposed for the treatment of agitation. However, the benefit and safety of these agents in TBI patients as well as their differential effects and interactions are uncertain. In addition, animal studies and observational studies have suggested impaired cognitive function with the use of certain antipsychotics and benzodiazepines. Hence, a safe and effective treatment for agitation, which does not interfere with neurological recovery, remains to be identified.
  
  
  
  With the help of Health Sciences librarian, we will design a search strategy in the following databases: PubMed, Ovid MEDLINE®, EMBASE, CINAHL, PsycINFO, Cochrane Library, Google Scholar, Directory of Open Access Journals, LILACS, Web of Science, and Prospero. A grey literature search will be performed using the resources suggested in CADTH's Grey Matters. We will include all randomized controlled, quasi-experimental, and observational studies with control groups. The population of interest is all patients, including children and adults, who have suffered a TBI. We will include studies in which agitation, not further defined, was the presenting symptom or one of the presenting symptoms. We will also include studies where agitation was not the presenting symptom but was measured as an outcome variable and studies assessing the safety of these pharmacological interventions in TBI patients. We will include studies evaluating all pharmacological interventions including beta-adrenergic blockers, typical and atypical antipsychotics, anticonvulsants, dopamine agonists, psychostimulants, antidepressants, alpha-2-adrenergic agonists, hypnotics, and anxiolytics.
  
  
  
  Although agitation is frequent following TBI and pharmacological agents that are often used, there is no consensus on the most efficacious and safest strategy to treat these complications. There is a need for an updated systematic review to summarize the evidence in order to inform practice and future research.
  
  
  
  PROSPERO CRD42016033140.
authors.affiliation: Pharmacy Department and Research Center, Hôpital du Sacré-Coeur de Montréal, 5400 Gouin West, Montreal, Quebec, H4J 1C5, Canada. david.williamson@umontreal.ca.|Faculté de pharmacie, Université de Montréal, Montréal, Canada. david.williamson@umontreal.ca.
authors.forename: David R
authors.initials: DR
authors.lastname: Williamson
authors.affiliation: Pharmacy Department and Research Center, Hôpital du Sacré-Coeur de Montréal, 5400 Gouin West, Montreal, Quebec, H4J 1C5, Canada.|Faculté de pharmacie, Université de Montréal, Montréal, Canada.
authors.forename: Anne Julie
authors.initials: AJ
authors.lastname: Frenette
authors.affiliation: Department of Pharmacy and Medicine, Mount Sinai Hospital, Toronto, Canada.|Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Burry
authors.affiliation: Faculté de pharmacie, Université de Montréal, Montréal, Canada.|Department of Pharmacy, McGill University Health Center, Montréal, Canada.
authors.forename: Marc M
authors.initials: MM
authors.lastname: Perreault
authors.affiliation: Department of Critical Care and Research Center, Hôpital du Sacré-Coeur de Montréal, Montréal, Canada.|Faculté de Médecine, Université de Montréal, Montréal, Canada.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Charbonney
authors.affiliation: Department of Medicine, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Canada.|Faculté de Médecine, Université de Sherbrooke, Sherbrooke, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Lamontagne
authors.affiliation: Department of Psychology, Hôpital du Sacré-Coeur de Montréal, Montréal, Canada.|Department of Psychology, Université du Québec à Montréal, Montréal, Canada.
authors.forename: Marie-Julie
authors.initials: MJ
authors.lastname: Potvin
authors.affiliation: Faculté de Médecine, Université de Montréal, Montréal, Canada.|Department of Neurosurgery, Hôpital du Sacré-Coeur de Montréal, Montréal, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Giguère
authors.affiliation: Department of Medicine, Interdepartmental Division of Critical Care Medicine, Mount Sinai Hospital, Toronto, Canada.|Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Mehta
authors.affiliation: Department of Critical Care and Research Center, Hôpital du Sacré-Coeur de Montréal, Montréal, Canada.|Faculté de Médecine, Université de Montréal, Montréal, Canada.
authors.forename: Francis
authors.initials: F
authors.lastname: Bernard
mesh_terms: D000293:Adolescent; D000328:Adult; D000070642:Brain Injuries, Traumatic / Q000150:complications* / Q000188:drug therapy; D002491:Central Nervous System Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D001523:Mental Disorders / Q000209:etiology / Q000517:prevention & control*; D000066553:Problem Behavior; D011595:Psychomotor Agitation / Q000188:drug therapy*; D012107:Research Design; D000078202:Systematic Reviews as Topic; D015201:Meta-Analysis as Topic
chemical_list: D002491:Central Nervous System Agents
keywords: Agitation; Pharmacological intervention; Traumatic brain injury