Pharmacological management for agitation and aggression in people with acquired brain injury.
BACKGROUND
Of the many psychiatric symptoms that may result from brain injury, agitation and/or aggression are often the most troublesome. It is therefore important to evaluate the efficacy of psychotropic medication used in its management.


OBJECTIVE
To evaluate the effects of drugs for agitation and/or aggression following acquired brain injury (ABI).


METHODS
We searched MEDLINE (1966-2002), EMBASE (1980-2002) and the Cochrane Controlled Trials Register (1996-2002), Web of Science Citation Index, reference lists of papers meeting the inclusion criteria and recent reviews. We handsearched Brain Injury and the Journal of Head Trauma Rehabilitation. There were no language restrictions.


METHODS
Randomised controlled trials (RCTs) that evaluated the efficacy of drugs acting on the central nervous system for agitation and/or aggression, secondary to ABI, in participants over 10 years of age. Studies using lower levels of evidence (i.e. case series studies, single case studies and controlled group comparison studies), were collated in an appendix.


METHODS
Two reviewers independently extracted data and assessed trial quality. Authors were contacted where necessary for additional information. Studies of patients within six months after brain injury and/or in a confusional state, were distinguished from those of patients more than six months post-injury, or who were not confused.


RESULTS
Six randomised controlled trials were identified. Four RCTs evaluated the beta-blockers, propranolol and pindolol, one RCT evaluated the central nervous system stimulant, methylphenidate and one RCT evaluated amantadine, a drug normally used in parkinsonism and related disorders. The best evidence of effectiveness in the management of agitation and/or aggression following ABI was for beta-blockers. Two RCTs found propranolol to be effective (one study early and one late after injury). However, these studies used relatively small numbers, have not been replicated, used large doses, and did not use a global outcome measure or long-term follow-up. Comparing early agitation to late aggression, there was no evidence for a differential drug response. Firm evidence that carbamazepine or valproate is effective in the management of agitation and/or aggression following ABI is lacking.


CONCLUSIONS
Numerous drugs have been tried in the management of aggression in ABI but without firm evidence of their efficacy. It is therefore important to choose drugs with few side effects and to monitor their effect. Beta-blockers have the best evidence for efficacy and deserve more attention. The lack of evidence highlights the need for better evaluations of drugs for this important problem.
Fleminger
S
S
Lishman Brain Injury Unit, Maudsley Hospital, Denmark Hill, London, UK, SE5 8AZ. s.fleminger@iop.kcl.ac.uk
Greenwood
R J
RJ
Oliver
D L
DL
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000374:Aggression; D000547:Amantadine / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy*; D001930:Brain Injuries / Q000523:psychology*; D006801:Humans; D008774:Methylphenidate / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010869:Pindolol / Q000627:therapeutic use; D011433:Propranolol / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
D000319:Adrenergic beta-Antagonists; D018696:Neuroprotective Agents; D008774:Methylphenidate; D011433:Propranolol; D000547:Amantadine; D010869:Pindolol