Pharmacological management for agitation and aggression in people with acquired brain injury
Abstract
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.
Objectives
To evaluate the effects of drugs for agitation and/or aggression following acquired brain injury (ABI).
Search 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.
Selection criteria
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.
Data collection and analysis
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.
Main 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.
Authors' 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.
Plain language summary
Beta‐blockers are the drugs with most evidence for relieving agitation and aggression in people with acquired brain injury, but more research is needed
People with brain injury often experience post‐traumatic amnesia that causes disorientation and agitation. This generally eases as amnesia recedes. However, agitation and aggression may occur or continue later, and cause great distress. A wide variety of drugs are used to try and ease these symptoms. However, the review found that there is no strong evidence about the effects of most of these drugs in people with brain injury. Adverse effects of these drugs may be particularly problematic for people with brain injury. Beta‐blockers are the drugs most supported by evidence of benefit at this stage, but more research is needed.
