Is there evidence for using anticonvulsants in the prevention and/or treatment of delirium among older adults?

Abstract

<h3>Introduction</h3> Delirium is an acute neuropsychiatric syndrome characterized by impaired attention, awareness and cognition. It develops over a short period of time (hours to days), represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day. The highest prevalence of delirium is found in the older adults, being particularly high in the hospitalized older adults. The highest incidence rates for delirium among the older adults are observed in the intensive care units, and in postoperative and palliative care settings. Delirium is associated with poorer clinical outcomes including a worsening of nutritional status, cognition and medical co-morbidities. It is associated with greater lengths and costs of hospitalization, and greater burden of care on the nursing staff. Delirium also increases the risk for developing cognitive impairment, institutionalization and death. The average medical care cost for individuals with delirium is more than two-and-a half times the cost for individuals without. Both non-pharmacologic and pharmacologic treatments are used in the management of delirium. Non-pharmacologic treatments that benefit older adults with delirium include frequent reorientation, making eye contact, frequent touching and using clear verbal instructions when talking to patients. Additionally, minimizing of sensory impairments including vision and hearing loss by use of assistive devices, reducing the use of physical restraints, providing treatment in a non-stimulating environment and minimizing staff and room changes, have proven beneficial as well. Pharmacotherapy is often used to treat the underlying causes of delirium in older adults, especially in the management of behaviors that are not managed by non-pharmacological strategies. Agents that have shown benefit among older adults with delirium include antipsychotics, cholinesterase inhibitors and benzodiazepines. Valproic acid derivatives have been used in the treatment of delirium among younger adults with some success. Many different mechanisms have been proposed for this, including the actions of valproic acid derivatives on the glutamatergic system, dopaminergic system, GABAergic system, Kynurenine Pathway. Oral or intravenous valproic acid preparations appear to be efficacious in delirium when antipsychotics and/or benzodiazepines are ineffective, the management requires large and/or frequent dosing of medications, or the medications cause significant adverse effects. Valproic acid derivatives have been beneficial in over 70% of the cases, with benefits noted in the first week of treatment, and the medication was well tolerated. Given the emerging evidence for the efficacy of valproic acid preparations among individuals with delirium, we decided to conduct a systematic review that examined the current evidence for using anticonvulsants in the prevention and/or treatment of delirium among older adults from published randomized control trials (RCTs). If there is good evidence for their use in the older adult population, then it would broaden the pharmaceutic options available to manage this serious condition among a vulnerable group of individuals. <h3>Methods</h3> A comprehensive search of databases: MEDLINE ALL (Ovid), Embase (Ovid), PsycINFO (Ovid), Web of Science Core Collection and Cochrane Central Register of Controlled was conducted. <h3>Results</h3> The search identified four RCTs that evaluated the use of anticonvulsants among older adults with delirium. One RCT evaluated the perioperative use of gabapentin among patients undergoing spinal surgery and the development of postoperative delirium. One RCT evaluated the relationship between the use of perioperative gabapentin and the development of postoperative delirium among patients undergoing spinal surgery and hip and knee arthroplasty. Two post-hoc analyses of RCTs that evaluated the use of gabapentin and pregabalin among patients undergoing total knee replacement (TKA) and total hip replacement (THA). The perioperative use of gabapentin reduced the incidence of postoperative delirium among older adults undergoing spinal surgery. The perioperative use of gabapentin did not reduce the rates, severity or duration of postoperative delirium among older adults who were undergoing spine and hip and knee arthroplasty. The perioperative use of gabapentin did not reduce the incidence or duration of postoperative delirium among older adults undergoing elective TKA. The perioperative use of pregabalin did not reduce the incidence of postoperative delirium among older adults undergoing elective THA. Gabapentin and pregabalin were well tolerated among the patients enrolled in these trials. There were no RCTs identified that evaluated the use of other anticonvulsants for the prevention and/or treatment of delirium among older adults. <h3>Conclusions</h3> Based on current evidence, the routine use of anticonvulsants for the prevention and/or treatment of delirium among older adults cannot be recommended.