Scoping review maps how agitation after traumatic brain injury is managed

Agitation is one of the most disruptive complications facing patients recovering from moderate to severe traumatic brain injury, and a new scoping review published in the Chinese Neurosurgical Journal finds that clinicians still lack a standardised way to treat it. The review, led by Irrum Aneela, Priya Kadam and Chandrasekaran Kaliaperumal, evaluated a decade of research on pharmacological and non-pharmacological strategies for managing agitation after traumatic brain injury and concluded that the evidence base remains thin, dominated by observational studies, surveys and small trials rather than large randomised controlled studies.

The scale of the underlying problem is considerable. Traumatic brain injury, caused when an external force such as a fall or road traffic accident damages the brain, is a leading cause of disability, mortality and morbidity worldwide. In the United States alone there were approximately 214,110 TBI-related hospitalisations in 2020 and 68,663 TBI-related deaths in 2023, figures that translate to more than 586 hospitalisations and 190 deaths per day. These estimates exclude injuries treated only in emergency departments, primary care or urgent care settings, as well as those that go untreated entirely.

Agitation itself, comprising restlessness, disinhibition, impulsive behaviour, variable anger, irritability and aggression, has been reported in 20 to 41 percent of patients during the early stage of recovery in acute care units and in up to 70 percent of patients in rehabilitation units. On acute care wards it affects 11 to 70 percent of patients after TBI and typically persists for one to fourteen days, sometimes longer, before discharge. The International Psychogeriatric Association defines agitation formally through criteria including behaviours attributed to cognitive impairment, behaviours present for two weeks or more that differ from a person’s normal conduct, and verbal or physical aggression or excessive motor activity that causes distress or impairs social or daily functioning.

Certain patients appear more vulnerable. Possible pre-morbid risk factors include a history of substance use, mood and personality disorders, criminal record, dysregulated aggression and antisocial behaviour, while a longer duration of lost consciousness and co-existing medical conditions may also contribute. Potential triggers during recovery include infection, poor sleep, frontal lobe injury, environmental overstimulation, pain and age. There is a strong relationship between agitated behaviour and frontal lobe injury, which produces disinhibition and reduced awareness of consequences. Agitation also prolongs post-traumatic amnesia and impairs motor and cognitive functioning, and disoriented patients risk falls, restraints, longer hospital stays and delayed rehabilitation, while families report strained relationships and clinical staff face heavier workloads and burnout.

Methodologically, the review followed PRISMA guidelines with a protocol pre-registered on PROSPERO (ID 1295903). The authors searched PubMed using MeSH and Boolean terms, Embase via Ovid with free-text mapping to subject headings, and Cochrane with free-text searches, covering studies published between 1 January 2015 and 9 March 2026. From 65 identified records, 13 papers were selected for the review after screening, with 40 papers excluded as irrelevant topics, eight as duplicates, three as paediatric studies and one as a letter. Qualitative studies were appraised with the Critical Appraisal Skills Programme checklist, and two reviewers working at separate sites discussed and resolved inclusion disputes by consensus.

On the non-pharmacological side, the review highlighted the importance of orienting the patient and the supportive role of family during acute recovery. A qualitative survey of 33 clinicians from 16 countries found that proactively removing potential sources of agitation, both patient-related and environmental, and using consistent, simple behavioural management reduced agitation in practice. A cross-sectional anonymous online survey of 331 clinicians managing agitation during early recovery found that the most frequently used non-pharmacological strategies were reducing noise levels, cited by 80 percent of respondents, and managing patients in single rooms, cited by 81 percent. The authors caution, however, that these findings reflect clinician opinion rather than methods supported by comparative trials.

Sleep emerged as another recurring theme. Observational studies and conference extracts found that many clinicians consider sleep essential for recovery, noting that low sleep efficacy was associated with greater agitation. One retrospective observational study found that on day one after moderate to severe traumatic brain injury, patients with agitation had lower sleep efficacy, suggesting that sleep hygiene strategies may help reduce agitation, although the association does not establish causation. Families, meanwhile, reported in 20 qualitative semi-structured interviews that their involvement during early recovery was beneficial, describing comforting strategies such as holding the patient’s hand, stroking the head and physical touch that helped the patient feel safe, along with adding familiar belongings to the environment to create a place of calm.

The pharmacological picture is more fragmented but includes some notable signals. In a double-blind randomised clinical trial of just 11 participants, five receiving oral olanzapine and six placebo, the antipsychotic olanzapine was effective at managing agitation during the post-traumatic amnesia phase following TBI, though not for the remaining duration of agitation, at doses ranging from 5 to 20 milligrams, with the drug noted to possibly cause confusion. A small case series of three male patients found short-term valproic acid useful for managing agitation at doses of 250 milligrams to 1 gram daily over 7 to 20 days, assessed with the Richmond Agitation-Sedation Scale and liver function monitoring. A systematic review of pharmacological interventions found amantadine and olanzapine reduced aggression while valproic acid may reduce agitation, but judged the quality of the underlying studies weak. A conference abstract reported that dextromethorphan and quinidine reduced agitation, with adverse effects of cognitive impairment and QT prolongation noted on electrocardiograms.

Sedation with dexmedetomidine, an agent that stimulates alpha-2 adrenergic receptors in the locus coeruleus, has also been trialled. One study found that within 72 hours of dexmedetomidine initiation the proportion of agitated patients decreased from 100 to 63 percent, but bradycardia occurred in 76 percent of patients and hypotension in 54 percent, making the agent potentially unsuitable for TBI patients with existing bradycardia or hypotension. The authors of that study advised caution because agitation assessment frequency varied and there was no control group. Separately, a 42-item survey of 219 physicians across 18 level 1 trauma intensive care units found that 72 percent believed alpha-2 adrenergic agonists were effective in managing agitation.

The review’s overarching conclusion is sobering: there is currently no consensus on the most efficacious and safest strategy to treat agitation after TBI, many clinicians report dissatisfaction with existing guidelines and insufficient training, and only one original randomised controlled trial was included, an olanzapine study that itself acknowledged blurred lines between treatment and placebo allocation. Most included studies were observational or reviews rather than randomised trials, constituting a limitation the authors flag directly. They call for future research with larger sample sizes, extending beyond intensive care to neurosurgery and neurology units, more stratified recruitment by age and time since injury, evaluation of antipsychotic dosing safety in patients with psychiatric histories, and personalisation of medication to individual medical histories. Until such trials materialise, the review suggests olanzapine and valproic acid may have short-term, interim uses in the acute setting under supervision, while the widely practised non-pharmacological measures, though broadly endorsed by clinicians, still await quantifiable evidence.

Subject of Research: Pharmacological and non-pharmacological management of agitation after traumatic brain injury

Article Title: Scoping review of pharmacological and non-pharmacological management of agitation in post traumatic brain injury patients

Article References: Aneela, I., Kadam, P., & Kaliaperumal, C. (2026). Scoping review of pharmacological and non-pharmacological management of agitation in post traumatic brain injury patients. Chinese Neurosurgical Journal, 12(1), Article 25. https://doi.org/10.1186/s41016-026-00445-7

Image Credits: AI Generated

DOI: 10.1186/s41016-026-00445-7

Keywords: traumatic brain injury, agitation, scoping review, olanzapine, valproic acid, dexmedetomidine, post-traumatic amnesia, non-pharmacological management, sleep hygiene, family involvement, intensive care, PROSPERO