Cognitive and Motor Function Effects of Antipsychotics in Traumatic Brain Injury: A Systematic Review of Pre-Clinical Studies.

Traumatic brain injury (TBI) survivors often suffer from agitated behaviors and will most likely receive pharmacological treatments. Choosing an optimal and safe treatment that will not interfere with neurological recovery remains controversial. By interfering with dopaminergic circuits, antipsychotics may impede processes important to cognitive recovery. Despite their frequent use, there have been no large randomized controlled studies of antipsychotics for the management of agitated behaviors during the acute TBI recovery period. We conducted a systematic review and meta-analysis of pre-clinical studies evaluating the effects of antipsychotics post-TBI on both cognitive and motor recovery. MEDLINE and Embase databases were searched up to August 2, 2023. Pre-clinical studies evaluating the effects of antipsychotics on cognitive and motor functions post-TBI were considered. Risk of bias was evaluated with the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. We identified 15 studies including a total of 1188 rodents, mostly conducted in male Sprague-Dawley rats using cortical impact injury. The analysis revealed no consistent effect of haloperidol on motor functions, but risperidone was associated with a significant impairment in motor function on day 5 post-injury (7.05 sec; 95% confidence interval [CI]: 1.47, 12.62; I2 = 92%). Other atypical antipsychotics did not result in impaired motor function. When evaluating cognitive function, haloperidol- (23.00 sec; 95% CI: 17.42-28.59; I2 = 7%) and risperidone-treated rats (24.27 sec; 95% CI: 16.18-32.36; I2 = 0%) were consistently impaired when compared to controls. In studies evaluating atypical antipsychotics, no impairments were observed. Clinicians should avoid the regular use of haloperidol and risperidone, and future human studies should be conducted with atypical antipsychotics.

The negative influence of chronic alcohol abuse on acute cognitive recovery after a traumatic brain injury.

OBJECTIVE: Cognitive recovery after a traumatic brain injury (TBI) may be negatively affected by a prior alcohol use disorder (AUD). This study aims to compare the cognitive recovery of patients who had comorbid TBI and AUD relative to TBI alone and investigate the influence of blood alcohol level (BAL) at hospital admission on this recovery. METHOD: The sample consisted of 42 patients who had sustained a TBI (mild or moderate) and had an AUD diagnosis (TBI+AUD), and 42 patients who had sustained a TBI alone (TBI). The Brief Cognitive Exam in Traumatology (EXACT), designed to evaluate cognitive functions in the acute phase of TBI was administered (± 2 weeks post-injury). RESULTS: After controlling for BAL at admission, the TBI+AUD group had a lower EXACT total score compared to the TBI group. The negative influence of age on the results was more pronounced in the TBI+AUD group. The number of intoxicated patients at admission was also higher in this group, although there was no correlation between BAL at admission and cognitive outcome. CONCLUSION: The presence of an AUD diagnosis seems to exert a greater negative influence on cognitive recovery following a mild/moderate TBI than BAL at admission, especially in older patients.

Cognitive profiles in the acute phase of traumatic brain injury according to injury severity.

Although several studies have documented the chronic phase of traumatic brain injury (TBI), few verified the nature and severity of cognitive impairments during the acute phase. Among the studies carried out during the acute phase, instrumental functions were rarely examined compared to attention, memory, and executive functions. This study aimed to compare the nature and intensity of cognitive problems in the acute phase according to TBI severity and age. It was hypothesized that cognitive impairments would increase in line with TBI severity and age, and that instrumental functions would be less affected in victims of mild or moderate TBI than in those with severe TBI. The Brief Cognitive Exam in Traumatology (EXACT), a new and reliable test specifically designed and validated to briefly assess global cognitive functioning during the acute phase, was administered to 319 mild to severe TBI victims (aged 16 to 96 years), within three months post-accident. The EXACT evaluates five domains: Language, Instrumental functions (other than language), Attention and working memory, Episodic memory, and Executive functions and behavioral regulation. Results confirmed the negative influence of TBI severity and age on global cognitive functioning. Also, compared to victims with a mild or moderate TBI, a higher proportion of those with a severe TBI presented impaired instrumental functions (calculation, praxis, and gnosis). Thus, during the acute phase, the nature and severity of cognitive impairments vary according to TBI severity.