Chronic administration of antipsychotics impede behavioral recovery after experimental traumatic brain injury

Abstract

Antipsychotics are often administered to traumatic brain injured (TBI) patients as a means of controlling agitation, albeit the rehabilitative consequences of this intervention are not well known. Hence, the goal of this study was to evaluate the effects of risperidone (RISP) and haloperidol (HAL) on behavioral outcome after experimental TBI. Anesthetized rats received either a cortical impact or sham injury and then were randomly assigned to five TBI (RISP 0.045 mg/kg, RISP 0.45 mg/kg, RISP 4.5 mg/kg, HAL 0.5 mg/kg, VEHicle 1 mL/kg) and three Sham (RISP 4.5 mg/kg, HAL 0.5 mg/kg, VEH 1 mL/kg) groups. Treatments began 24 hrs after surgery and were provided once daily for 19 days. Behavior was assessed with established motor (beambalance/walk) and cognitive (spatial learning/memory in a water maze) tasks on post-operative days 1-5 and 14-19, respectively. RISP and HAL delayed motor recovery, impaired the acquisition of spatial learning, and slowed swim speed relative to VEH in both TBI and sham groups. These data indicate that chronic administration of RISP and HAL impede behavioral recovery after TBI and impair performance in uninjured controls.

Traumatic Brain Injury-Induced Cognitive and Histological Deficits Are Attenuated by Delayed and Chronic Treatment with the 5-HT1A-Receptor Agonist Buspirone

“…In addition to 5-HT 1A -receptor agonist properties, BUS is also a partial D 2 antagonist (Coop and McNaughton, 1991;McMillen et al, 1983), which could explain, in part, the worsening effect seen with the higher BUS dose, if it surpassed its threshold for 5-HT 1A -receptor activation and instead antagonized D 2 receptors. Support for this notion derives from previous work in our laboratory demonstrating that the D 2 -receptor antagonist haloperidol impedes the ability of rats to successfully navigate a water maze task to find the escape platform Kline et al, 2007aKline et al, ,2008. Water maze performance is also impaired by haloperidol in a fluid percussion model of TBI (Wilson et al, 2003).…”

Virtual reality-based therapy for the treatment of balance deficits in patients receiving inpatient rehabilitation for traumatic brain injury

“…[12][13][14][15] Physical damage associated with TBI can involve trauma to any of the primary neurological centers of balance maintenance, including the motor cortex, parietal cortex, brain stem, vestibular system, basal ganglia and/or the cerebellum, [12,19,55] and can also include damage to other body systems that occur at the same time as the TBI, including contusions, bone fractures, and spinal cord injury. Sensory deficits include the reduction of information from the primary sensory systems involved in balance, including the visual, vestibular or proprioceptive systems, or an inability to appropriately utilize this sensory information.…”

“…[10] These impairments are often the result of diminished abilities of one of the many systems involved in balance and posture maintenance, [11] which can be attributed to physical damage to the brain and central nervous system, sensory disruption in receiving information from the body systems involved in balance, [12] muscle wasting from long periods of bed rest [10] and medications used to treat co-occurring issues. [12][13][14][15] Balance deficits are of particular importance in regards to the treatment of patients after TBI. Diminished balance ability has been shown to be associated with longer inpatient rehabilitation length of stay, [7,10] increased risk of falling, [16] slowed recovery, increased medical complications [10] and gait abnormalities.…”

Rehabilitation Considerations for Traumatic Brain Injury in the Geriatric Population: Epidemiology, Neurobiology, Prognosis, and Management

“…All patients with TBI, and elderly patients in particular, are also more likely to experience side effects from anticholinergic medications [82]. These include minimizing the use of anticholinergic, antidopaminergic, and antihistamine drugs, each of which are commonly used as agitation management, urinary, bowel and sleep maintenance medications [83]. Benzodiazepines for anxiety and atypical GABA agonists for sleep disturbances are also very commonly used in the elderly, and their use can negatively impact recovery following TBI [84].…”

“…Typical antipsychotics, commonly used to control insomnia and agitation, are often used in geriatric patients, and have been demonstrated to delay motor recovery and spatial learning following TBI [83,85]. Prolonged use of antiepileptic medications such as phenytoin also negatively impacts neurological recovery, and when possible, the duration should be reduced to the acute period when used for post-traumatic prophylaxis [86•, 87].…”