Lithium Carbonate

Lithium carbonate has been used for many years in the treatment of mania and bipolar disorder (Kim 2002). It has been suggested that mood disorders, such as mania, occurring after TBI, may contribute to the development of aggression (Kim 2002; Wroblewski et al. 1997). In the search for a pharmacological agent that reduces aggression following TBI with limited side effects in comparison to antipsychotics and benzodiazepines, lithium has been tried. Lithium carbonate also functions as a mood stabilizer.

Table: Effects of Lithium Carbonate on Aggressive Behaviour


Lithium carbonate was used in a series of case reports with 10 individuals with either TBI or stroke (Glenn et al. 1989). The authors reported favourable outcomes for the majority of patients (i.e. a decrease in observed aggressive, combative, or self-destructive behaviour or severe affective instability). However, this study highlights that there is a high risk of potential neurotoxicity among individuals with brain injuries, specifically in combination with neuroleptic drugs. 


There is Level 4 evidence to suggest that an antimanic agent (lithium carbonate) reduces aggressive/agitated behaviour following a brain injury.


Lithium may reduce behavioural problems but is associated with a high risk of neurotoxicity.


Quetiapine (Seroquel)

Quetiapine has been used to reduce aggressive behaviour among those diagnosed with schizophrenia and Alzheimer’s disease (Volavka et al. 2004; Webb & Glueckauf 1994). A closer examination of its impact within a brain injury population is discussed below. 

Table: Effects of Quetiapine on Aggressive Behaviour


In one case series, quetiapine assisted in helping to reduce aggressive behaviour in seven individuals (Kim & Bijlani 2006). They also noted significant improvements in the Overt Aggression Scale-Modified (OAS-M), the CGI scores, and the overall scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Quetiapine may be considered as an alternative to haloperidol or chlorpromazine if additional research finds it is just as effective in treating aggressive behaviours without the side effects (Kim & Bijlani 2006).


There is Level 4 evidence to suggest that quetiapine helps reduce aggressive behaviour.


Although there is evidence to suggest that quetiapine does help reduce aggressive behaviour, more research is needed.



Ziprasidone has been approved for acute agitation in those diagnosed with schizophrenia. It has also been found to work in the treatment of acute mania, often associated with bipolar disorder. For those who sustain a TBI, the period of post traumatic amnesia (PTA) is defined as a period during which the individual is disorientated, have difficulty learning new concepts, and/or suffer from behaviour alterations (Brooke et al. 1992). Researchers believe that these behaviour alternations may result from the individual’s lack of self-awareness which may be related to memory alterations that appear after the injury (Noé et al. 2007).

Table: Effects of Ziprasidone on Agitation


Noe et al. (2007) studied individuals who were still in PTA stage at admission to rehabilitation. Within these participants, a decrease in agitation scores was reported during the first 2 weeks of ziprasidone administration. It was also noted that all who participated tolerated the medication with no clinical side effects observed. A larger RCT would be beneficial before any firm conclusions are made.


There is Level 4 evidence from one study to suggest that ziprasidone assists in the controlling of agitation post TBI.


Ziprasidone in one small study has been shown to assist in the controlling of agitation; however more research is needed.



Haloperidol is a psychotropic drug found to reduce agitation. It also blocks or disrupts dopamine receptors. Thus, while it improves agitation, there is a theoretical concern that it may impede recovery by reducing arousal.

Table: Effects of Haloperidol on Agitation


In a retrospective chart review, agitation was managed in 11 patients with haloperidol and in 15 patients without haloperidol (Rao et al. 1985). No significant differences were found between the two groups with regards to success of rehabilitation outcome; however, none of the patients in the treatment group obtained independence in intellectual skills (Rao et al. 1985).


There is Level 4 evidence that haloperidol does not have a negative effect on the success of rehabilitation.  


Haloperidol appears to have little negative effect on recovery following TBI.


Droperidol (Inapsine)

Droperidol is a butyrophenone antipsychotic agent that closely resembles haloperidol in structure. It has been used for the treatment of psychosis in Europe (Stanislav & Childs 2000).

Table: Effects of Droperidol on Improving Behaviour


When an individual is agitated, not only is the effectiveness of the medication administered important but also the time it takes to have a calming effect. One retrospective controlled trial found that a single-dose of droperidol calmed patients displaying agitated behaviour faster than other drugs (haloperidol, lorazepam, and diphenhydramine; Stanislav & Childs 2000). The study also found that droperidol calmed individuals without heavily sedating the patients like some of the comparative medications did. It is worth noting however that a large proportion of the sample had psychiatric co-morbidities; this should be kept in mind when generalizing the findings.


There is Level 4 evidence that administration of a single-dose droperidol calms agitated patients with ABI more quickly than other agents.


Droperidol may be an effective agent for calming agitated patients.