Pharmacological interventions for agitated behaviours in patients with traumatic brain injury: a systematic review

Objective The aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain injury (TBI).Methods We performed a search strategy in PubMed, OvidMEDLINE, Embase, CINAHL, PsycINFO, Cochrane Library, Googl...

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Main Authors: Sangeeta Mehta, David Williamson, Anne Julie Frenette, Lisa D Burry, Marc Perreault, Emmanuel Charbonney, Francois Lamontagne, Marie-Julie Potvin, Jean-Francois Giguère, Francis Bernard
Format: Article
Language:English
Published: BMJ Publishing Group 2019-07-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/9/7/e029604.full
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author Sangeeta Mehta
David Williamson
Anne Julie Frenette
Lisa D Burry
Marc Perreault
Emmanuel Charbonney
Francois Lamontagne
Marie-Julie Potvin
Jean-Francois Giguère
Francis Bernard
author_facet Sangeeta Mehta
David Williamson
Anne Julie Frenette
Lisa D Burry
Marc Perreault
Emmanuel Charbonney
Francois Lamontagne
Marie-Julie Potvin
Jean-Francois Giguère
Francis Bernard
author_sort Sangeeta Mehta
collection DOAJ
description Objective The aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain injury (TBI).Methods We performed a search strategy in PubMed, OvidMEDLINE, Embase, CINAHL, PsycINFO, Cochrane Library, Google Scholar, Directory of Open Access Journals, LILACS, Web of Science and Prospero (up to 10 December 2018) for published and unpublished evidence on the risks and benefits of 9 prespecified medications classes used to control agitated behaviours following TBI. We included all randomised controlled trials, quasi-experimental and observational studies examining the effects of medications administered to control agitated behaviours in TBI patients. Included studies were classified into three mutually exclusive categories: (1) agitated behaviour was the presenting symptom; (2) agitated behaviour was not the presenting symptom, but was measured as an outcome variable; and (3) safety of pharmacological interventions administered to control agitated behaviours was measured.Results Among the 181 articles assessed for eligibility, 21 studies were included. Of the studies suggesting possible benefits, propranolol reduced maximum intensities of agitation per week and physical restraint use, methylphenidate improved anger measures following 6 weeks of treatment, valproic acid reduced weekly agitated behaviour scale ratings and olanzapine reduced irritability, aggressiveness and insomnia between weeks 1 and 3 of treatment. Amantadine showed variable effects and may increase the risk of agitation in the critically ill. In three studies evaluating safety outcomes, antipsychotics were associated with an increased duration of post-traumatic amnesia (PTA) in unadjusted analyses. Small sample sizes, heterogeneity and an unclear risk of bias were limits.Conclusions Propranolol, methylphenidate, valproic acid and olanzapine may offer some benefit; however, they need to be further studied. Antipsychotics may increase the length of PTA. More studies on tailored interventions and continuous evaluation of safety and efficacy throughout acute, rehabilitation and outpatient settings are needed.PROSPERO registration number CRD42016033140
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spelling doaj-art-85ce86b298a448aba98a49b87fd84ef52024-11-28T10:30:10ZengBMJ Publishing GroupBMJ Open2044-60552019-07-019710.1136/bmjopen-2019-029604Pharmacological interventions for agitated behaviours in patients with traumatic brain injury: a systematic reviewSangeeta Mehta0David Williamson1Anne Julie Frenette2Lisa D Burry3Marc Perreault4Emmanuel Charbonney5Francois Lamontagne6Marie-Julie Potvin7Jean-Francois Giguère8Francis Bernard9Department of Medicine, Sinai Health System, Toronto, Ontario, Canada8 Pharmacy, Université de Montréal, Montreal, Quebec, Canada1 Pharmacy, Université de Montréal, Montreal, Quebec, Canada3 Pharmacy, Mount Sinai Hospital, Toronto, Ontario, CanadaFaculté de Pharmacie, Université de Montréal, Montreal, Quebec, CanadaCentre de recherche, Centre Hospitalier de l`Université de Montréal, Montreal, Quebec, CanadaDepartment of Medicine and Centre de recherche du CHU de Sherbrooke, Sherbrooke, Quebec, Canada8 Psychology, Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada9 Neurosurgery, Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, CanadaDepartment of Medicine, Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, CanadaObjective The aim of this systematic review was to assess the efficacy and safety of pharmacological agents in the management of agitated behaviours following traumatic brain injury (TBI).Methods We performed a search strategy in PubMed, OvidMEDLINE, Embase, CINAHL, PsycINFO, Cochrane Library, Google Scholar, Directory of Open Access Journals, LILACS, Web of Science and Prospero (up to 10 December 2018) for published and unpublished evidence on the risks and benefits of 9 prespecified medications classes used to control agitated behaviours following TBI. We included all randomised controlled trials, quasi-experimental and observational studies examining the effects of medications administered to control agitated behaviours in TBI patients. Included studies were classified into three mutually exclusive categories: (1) agitated behaviour was the presenting symptom; (2) agitated behaviour was not the presenting symptom, but was measured as an outcome variable; and (3) safety of pharmacological interventions administered to control agitated behaviours was measured.Results Among the 181 articles assessed for eligibility, 21 studies were included. Of the studies suggesting possible benefits, propranolol reduced maximum intensities of agitation per week and physical restraint use, methylphenidate improved anger measures following 6 weeks of treatment, valproic acid reduced weekly agitated behaviour scale ratings and olanzapine reduced irritability, aggressiveness and insomnia between weeks 1 and 3 of treatment. Amantadine showed variable effects and may increase the risk of agitation in the critically ill. In three studies evaluating safety outcomes, antipsychotics were associated with an increased duration of post-traumatic amnesia (PTA) in unadjusted analyses. Small sample sizes, heterogeneity and an unclear risk of bias were limits.Conclusions Propranolol, methylphenidate, valproic acid and olanzapine may offer some benefit; however, they need to be further studied. Antipsychotics may increase the length of PTA. More studies on tailored interventions and continuous evaluation of safety and efficacy throughout acute, rehabilitation and outpatient settings are needed.PROSPERO registration number CRD42016033140https://bmjopen.bmj.com/content/9/7/e029604.full
spellingShingle Sangeeta Mehta
David Williamson
Anne Julie Frenette
Lisa D Burry
Marc Perreault
Emmanuel Charbonney
Francois Lamontagne
Marie-Julie Potvin
Jean-Francois Giguère
Francis Bernard
Pharmacological interventions for agitated behaviours in patients with traumatic brain injury: a systematic review
BMJ Open
title Pharmacological interventions for agitated behaviours in patients with traumatic brain injury: a systematic review
title_full Pharmacological interventions for agitated behaviours in patients with traumatic brain injury: a systematic review
title_fullStr Pharmacological interventions for agitated behaviours in patients with traumatic brain injury: a systematic review
title_full_unstemmed Pharmacological interventions for agitated behaviours in patients with traumatic brain injury: a systematic review
title_short Pharmacological interventions for agitated behaviours in patients with traumatic brain injury: a systematic review
title_sort pharmacological interventions for agitated behaviours in patients with traumatic brain injury a systematic review
url https://bmjopen.bmj.com/content/9/7/e029604.full
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