Table 1

Study characteristics

Study/year
(N)
Publication/countryStudy designStudy focus/populationInterventional arm/populationComparative arm/populationLocation at randomisationTiming from TBI at randomisationTBI description
1. Agitated behaviour as the presenting symptom
Brooke, et al 31/1992
(n=21)
Published
USA
RCT parallelAgitation
Mean age: 31
87 men and 13 women
Propranolol 60–420 mg/dayPlaceboLevel 1 trauma and rehabilitation centreN/ASevere blunt TBI
Mooney, Hass32/1993
(n=38)
Published
USA
Randomised
Pre–post
Anger
Mean age: 29±10
Male gender: 100%
Methylphenidate 30 mg/dayPlaceboOutpatient6 months or more (mean 27±21 months)Severe blunt TBI
Yablon, et al 33/2010
(n=79)
Abstract
USA
RCT parallelConfusion
Age and gender not reported
Amantadine
100 mg twice daily × 14 days
PlaceboInpatient brain injury unit of a rehabilitation hospital≤6 monthsTBI not further defined
Hammond, et al 34/2014
(n=76)
Published
USA
RCT parallelIrritability and aggressionAmantadine 100 mg twice daily
Mean age: 40±13
Male gender: 74.4%
Placebo
38±12
Male gender: 80.5%
Outpatient≥6 months following a TBIBlunt TBI
Beresford, et al 37/2015
(n=50)
Abstract
USA
RCT parallelAgitation
Mean age: 47±14
46 men and 4 women
Valproic acid for level 50–100 μg/mLPlaceboOutpatient>1 year following TBIMild and moderate TBI
Hammond, et al 35/2015
(n=168)
Published
USA
RCT parallelIrritability and aggressionAmantadine
100 mg twice daily
Mean age: 40±13
Male gender: 80.5%
Placebo
Mean age: 38±12
Male gender: 74.4%
Outpatient≥6 months following a TBIBlunt TBI
Maturana Waidele, Maturana Rodillo38/2009
(n=31)
Published
Chile
Prospective double-blindRestlessness, irritability, aggression, insomnia
Age and gender not reported
Olanzapine (dose not specified)PlaceboOutpatientN/ATBI not further defined
Gramish, et al 36/2017
(n=139)
Published
USA
Retrospective observationalAgitationAmantadine 100 mg twice daily
Mean age: 42±17
Male gender: 81.4%
No amantadine
Mean age: 48±21
Male gender: 76.8%
Adult trauma ICUAcute TBITBI not further defined
2. Agitated behaviour is not the presenting symptom
Study/year
(N)
Publication/countryStudy designStudy focusInterventional armComparative armLocation at randomisationTiming from TBI at randomisationTBI description
Schneider42/1999
(n=10)
Published
USA
RCT parallelCognitive function and behaviour
Mean age: 31
7 men and 3 women
Amantadine 50 mg twice daily increased to 150 mg twice dailyPlaceboOutpatientN/AModerate and severe TBI
Meythaler, et al 41/2001
(n=9)
Published
USA
RCT crossoverRecovery and arousal
Age and gender not reported
SertralinePlaceboInpatient rehabilitation<2 weeks of TBISevere TBI
Meythaler, et al 43/2002
(n=35)
Published
USA
RCT crossoverNeurological recovery
Mean age: 31
26 men and 9 women
AmantadinePlaceboEmergency departmentBetween 4 days and 6 weeks following TBISevere blunt TBI
Banos, et al 39/2010
(n=99)
Published
USA
RCT parallelCognitive function and behaviourSertraline
Mean age: 35±17
Male gender: 79%
Placebo
Mean age: 35±16
Male gender: 66%
Level 1 trauma centre inpatients<8 weeks of TBIModerate and severe TBI
Giacino, et al 40/2012
(n=184)
Published
USA, Denmark, Canada
RCT parallelFunctional recoveryAmantadine
Mean age: 35±15
Male gender: 74%
Placebo
Mean age: 37±15
Male gender: 71%
Inpatients4–16 weeks following TBIVegetative or minimally conscious TBI
Tramontana, et al 44/2014
(n=22 but 13 completed the study)
Published
USA
RCT crossoverAttention
Mean age: 29±9
Male gender: 69%
LisdexamfetaminePlaceboOutpatient6–34 months (mean 15.6+/-10 months) since TBIModerate and severe TBI
Johansson, et al 46 2014
(n=24)
Published
Sweden
RCT CrossoverMental fatigue and cognition
Mean age 39±11
Male gender: 50%
Methylphenidate
5 mg and 20 mg tid
PlaceboOutpatient>12 months following TBIMild or moderate TBI
Fann, et al 45/2017
(n=62)
Published
USA
RCT parallelMajor depressionSertraline
Mean age: 38±12
Male gender: 74%
Placebo
Mean age: 37±13
Male gender: 77%
Level 1 trauma centre<1 year of TBIModerate and severe TBI
Hart, et al 47/2017
(n=32)
Published
USA
RCT parallelCognitive functionDextroamphetamine
Mean age: 39±16
Male gender: 65%
Placebo
Mean age: 39±18
Male gender: 100%
TBI rehabilitation unit<6 months of TBIModerate and severe TBI
3. Studies assessing the safety of pharmacological agents used for agitated behaviours in TBI
Rao, et al 50/1985
(n=26)
Published
USA
Retrospective observationalRehabilitation outcomesHaloperidol
Median age: 34
Gender not reported
No haloperidol
Median age: 22
Gender not reported
Trauma and rehabilitation centreFrom admissionSevere closed head injury
Mysiw, et al 49/2006
(n=182)
Published
USA
Retrospective cohortCognitive and motor recovery
Mean age: 36
Male gender: 74%
Narcotics, benzodiazepines and neurolepticsNo CNS active medicationsLevel one trauma centre and rehabilitation centreFrom admissionTBI
Kooda, et al 51/2015
(n=195)
Abstract
USA
Retrospective observationalDuration of post-traumatic amnesia
Age and gender not reported
AntipsychoticsNo antipsychoticLevel one trauma centre and rehabilitation centreFrom admissionTBI
Anderson, et al 48/2016
(n=101)
Published
USA
Retrospective cohortSeizures, neuroleptic malignant syndrome, QTc prolongation, extrapyramidal symptoms, haematological disturbancesHaloperidol
Median age: 32
Male gender: 87%
No haloperidol
Median age: 47
Male gender: 61%
InpatientsFrom admissionModerate and severe TBI
  • CNS, Central Nervous System; RCT, Randomized controlled trial; TBI, traumatic brain injury.