Positive behavioural disturbances in the rehabilitation phase after severe traumatic brain injury: an historic cohort study

Background Antipsychotic drugs (APDs) are used to manage traumatic brain injury (TBI)-induced behavioral disturbances, such as agitation and aggression. However, APDs exhibiting D2 receptor antagonism impede cognitive recovery after experimental TBI. Hence, empirical evaluation of APDs with different mechanistic actions is warranted. Aripiprazole (ARIP) is a D2 and 5-HT1A receptor agonist; pharmacotherapies with these properties enhance cognition after TBI. Objective To test the hypothesis that ARIP would increase behavioral performance and decrease histopathology after TBI. Methods Adult male rats were subjected to either a controlled cortical impact (CCI) or sham injury and then randomly assigned to ARIP (0.1 or 1.0 mg/kg) or VEH (1.0 mL/kg, saline vehicle) groups. Treatments began 24 hr after surgery and were administered once daily for 19 days. Motor (beam-balance/beam-walk) and cognitive (Morris water maze) performance was assessed on post-operative days 1-5 and 14-19, respectively, followed by quantification of hippocampal CA1/3 neuron survival and cortical lesion volume. Results Beam-balance was significantly improved in the CCI + ARIP (1.0 mg/kg) group vs. CCI + ARIP (0.1 mg/kg) and CCI + VEH [p<0.05]. Spatial learning and memory retention were significantly improved in the CCI + ARIP (0.1 mg/kg) group vs. the CCI + ARIP (1.0 mg/kg) and CCI + VEH groups [p<0.05]. Both doses of ARIP reduced lesion size and CA3 cell loss vs. VEH [p<0.05]. Importantly, neither dose of ARIP impeded functional recovery as previously reported with other APDs. Conclusion These findings support the hypothesis and endorse ARIP as a safer APD for alleviating behavioral disturbances after TBI.

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“…20 Antipsychotic drugs (APDs) are frequently used in the context of attenuating agitation and aggression during the recovery phase. 21-25…”

Section: Introductionmentioning

confidence: 99%

Relative to Typical Antipsychotic Drugs, Aripiprazole Is a Safer Alternative for Alleviating Behavioral Disturbances After Experimental Brain Trauma

Phelps

Bondi

Mattiola

et al. 2016

Neurorehabil Neural Repair

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“…También puede haber un proceso de aprendizaje en las tareas realizadas, aunque lo verdaderamente interesante es el cambio observado en el comportamiento del paciente. En este sentido es importante destacar que el entrenamiento y el refuerzo en las capacidades atencionales y de los procesos ejecutivos han ayudado, cuando menos, a compensar las dificultades conductuales (Prigatano y Wong, 1999;Harmsen, Geurts, Fasotti y Behart, 2004). Es interesante destacar la necesidad de trabajar las capacidades cognitivas alteradas a la vez que se llega a un acuerdo con el paciente sobre los objetivos a conseguir.…”

Section: Discussionunclassified

“…8. Se corrobora la eficacia de la rehabilitación cognitiva (Harmsen et al, 2004). De manera que se puede explicar las alteraciones funcionales por las dificultades cognitivas.…”

Section: Discussionunclassified

Tratamiento neuropsicológico de problemas de control de impulsos en un caso de traumatismo craneoencefélico frontal: estudio de un caso [Neuropsychological treatment of impulse control in traumatic frontal brain injury: a case study]

Blázquez¹,

Ríos-Lago

Paúl³

et al. 2004

Acción psicol.

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“…We have therefore chosen olanzapine as the active intervention for this placebo-controlled randomised controlled trial. Current evidence for the use of antipsychotics for the management of neurobehavioural symptoms during PTA is limited to case series with no formal comparison condition [19,32,42,43]. Selection of a placebo comparator minimises bias and allows for collection of a higher level of evidence than that presently available.…”

Section: Introductionmentioning

confidence: 99%

Use of olanzapine to treat agitation in traumatic brain injury: study protocol for a randomised controlled trial

Phyland

McKay

Olver

et al. 2020

Trials

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Background: Agitation is common in the early stages of recovery from traumatic brain injury (TBI), when patients are in post-traumatic amnesia (PTA). Agitation is associated with risk of harm to patients and caregivers. Recent guidelines recommend that agitation during PTA is managed using environmental modifications. Agitation is also frequently treated pharmacologically, with the use of atypical antipsychotics such as olanzapine among the most common. This is despite a lack of well-designed studies to support the use of antipsychotics within this context. This study will be a double-blind, placebo-controlled randomised controlled trial. We will examine the efficacy, safety, cost-effectiveness and outcomes associated with the use of olanzapine for reducing agitation in patients in PTA following TBI over and above recommended environmental management. Methods: Fifty-eight TBI rehabilitation inpatients who are in PTA and are agitated will receive olanzapine or placebo for the duration of PTA. All participants will additionally receive optimal environmental management for agitation. Measures of agitation, PTA and health will be undertaken at baseline. Treatment administration will begin at a dose of 5 mg daily and may be escalated to a maximum dose of 20 mg per day. Throughout the treatment period, agitation and PTA will be measured daily, and adverse events monitored weekly. Efficacy will be assessed by treatment group comparison of average Agitated Behaviour Scale scores during PTA. Participants will cease treatment upon emergence from PTA. Agitation levels will continue to be monitored for a further 2 weeks, posttreatment measures of health will be undertaken and cognitive and functional status will be assessed. Level of agitation and functional health will be assessed at hospital discharge. At 3 months post-discharge, functional outcomes and health service utilisation will be measured.

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Positive behavioural disturbances in the rehabilitation phase after severe traumatic brain injury: an historic cohort study

Cited by 27 publications

References 22 publications

Relative to Typical Antipsychotic Drugs, Aripiprazole Is a Safer Alternative for Alleviating Behavioral Disturbances After Experimental Brain Trauma

Relative to Typical Antipsychotic Drugs, Aripiprazole Is a Safer Alternative for Alleviating Behavioral Disturbances After Experimental Brain Trauma

Tratamiento neuropsicológico de problemas de control de impulsos en un caso de traumatismo craneoencefélico frontal: estudio de un caso [Neuropsychological treatment of impulse control in traumatic frontal brain injury: a case study]

Use of olanzapine to treat agitation in traumatic brain injury: study protocol for a randomised controlled trial

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