Table 2

RCTs of pharmacological interventions of aggression in post-TBI adults

Author (year)Drug doseRCT designNo of participantsOutcome measureFindings
Psychostimulant
Mooney (1993)55Methylphenidate 30 mg dailyParallel single blind designTraetment:19
Placebo:19		POMS-Anger hostility scoreSignificantly effective in anger reduction
Speech (1993)56Methylphenidate 0.3 mg/kg two times a dayCross-over12 closed head injury patientsKAS-belligerence scoreNS
Dopaminergic
Schnieder (1999)57Amantadine 100–300 mg/dayCross-over10 patients with TBINeurobehavioural Rating ScaleNS
Hammond (2014)58Amantadine 100 mg two times a dayParallel design76NPI-I+NPI-ANS for the whole group but in a subgroup, amantadine was significantly better
Hammond (2015)59Amantadine 100 mg two times a dayParallel design168NPI-INS, both groups showed large improvements
Hammond (2017)60Amantadine 100 mg two times a dayParallel design118NPI-ITwo items out of many showed significantly better outcome in the amantadine group
Beta-blockers
Greendyke (1986a)61Propranolol 80–520 mg/dayCross-over9 patients with ABIObserved frequency of aggressive behaviourPropranolol significantly reduced assaultive behaviour
Greendyke (1986b)62Pindolol 10–60 mg/ dayCross-over11 patients with ABI (possible overlap with participants in 1986a study; not known)Observed frequency of aggressive behaviourPindolol significantly reduced assaultive behaviour
Greendyke (1989)63Pindolol 5–20 mg/dayCross-over10 patients with ABIOASNS
Brooke (1992)64Propranolol 60–420 mg/day (recommended maximum is 320 mg/day)Parallel designPropranolol:11
Placebo:10		OASPropranolol group showed less intense but same frequency of assaults compared to the placebo group received more physical restraints

  • ABI, acquired brain injury; KAS, Katz Adjustment Scale; NPI-A, Neuropsychiatry Inventory-Aggression; NPI-I, NPI-Irritability; NS, non-significant; OAS, Overt Aggression Scale; POMS, Profile of Mood States; RCT, randomised controlled trial; TBI, traumatic brain injury.