Management of delirium in older adults: challenges and opportunities

Delirium is a vexing clinical problem in hospitalized older adults. Despite the established association between delirium and death, morbidity, institutionalization, and patient distress (Siddiqi et al., 2006), few high-quality studies examining the management of delirium in older adults exist. Delirium management strategies can be broadly divided into those addressing prevention or treatment, as well as pharmacological and non-pharmacological modalities. Additional considerations include peri-operative and post-operative delirium management and management of delirium in the intensive care unit (ICU). Among hospitalized older adults, multicomponent non-pharmacological interventions have the best evidence for primary prevention of delirium. Such strategies, ideally delivered by an interdisciplinary team, include early mobilization, pain management, infection prevention, use of vision and hearing aids, avoidance of sleep disruption, adequate hydration and nutrition, re-orientation, cognitive stimulation, and review of psychoactive medications. A meta-analysis of 14 interventional studies found that implementation of the Hospital Elder Life Program (Inouye et al., 1999), a multicomponent interdisciplinary intervention, reduced the risk of incident delirium by 53% (OR 0.47 [95% CI, 0.38–0.58]) among hospitalized, non-ICU patients age 65 years and older (Hshieh et al., 2015). On the other hand, there is no high-quality evidence supporting the use of multi-component interventions to treat deliriumonce it has developed. Despite widespread use of pharmacological treatments, particularly antipsychotics, to manage delirium in hospitalized patients, most studies show no benefit in the use of medications to either prevent or treat delirium in hospitalized older adults (outside of specific cases such as alcohol-withdrawal delirium) (Oh et al., 2017). Medications studied in randomized, placebo-controlled trials for either prevention or treatment of delirium in older adults include haloperidol, atypical antipsychotics (aripiprazole, risperidone, olanzapine, quetiapine), melatonin, ramelteon, gabapentin, pregabalin, ondansetron, donepezil, methylprednisolone (at anesthetic induction), and dexmedetomidine (in the ICU and peri-operatively) (Oh et al., 2017). Only the centrally acting alpha-2 agonist dexmedetomidine has shown benefit in reducing the incidence and duration of ICU delirium (Flükiger et al., 2018). The lack of evidence-based pharmacological treatment options presents a conundrum for clinicians managing patients with delirium, particularly those with hyperactive delirium who may have psychosis, severe agitation, and are distressed. In their systematic review published in this issue of International Psychogeriatrics, Gupta et al. (2022) note that anticonvulsants are used clinically to manage delirium, with observational studies suggesting some benefit in the use of valproic acid to treat delirium. However, as the authors note, these studies were conducted in adults across the lifespan and the findings may not generalize to older adults, the population at highest risk of delirium. In order to critically appraise the evidence for this class of medication in managing delirium in older adults, they performed a systematic review with the goal of identifying randomized controlled trials (RCTs) examining the use of anticonvulsants to prevent or treat delirium in this population. Gupta et al. (2022) identified findings from only four RCTs (two primary analyses and two post-hoc analyses) in their review, all involving gabapentinoids (pregabalin or gabapentin), and all in patients undergoing orthopedic or spinal surgeries. The putative mechanism of gabapentinoids in delirium prevention in this population is primarily via opioidsparing (Fabritius et al., 2017). This is in contrast to the hypothetical mechanism of valproic acid in preventing and treating delirium, which is not well elucidated, but is postulated to be through neuromodulatory effects resulting in reduced inflammation, oxidative stress, and transcriptional changes that are implicated in the pathophysiology of delirium (Sher et al., 2015). Of the four studies that Gupta et al. (2022) identified, only one has positive findings: a pilot double-blind, placebo-controlled RCT with the primary aim of examining the use of gabapentin versus placebo in addition to opioid medication for postoperative pain management in 21 patients aged 45 years and older undergoing spinal surgery. In this study, the authors found that zero out of nine participants receiving gabapentin experienced International Psychogeriatrics (2022), 34:10, 861–864 © International Psychogeriatric Association 2021