Is daridorexant (Quviviq) effective for treating delirium?

Daridorexant for Delirium

Daridorexant is not currently recommended for routine treatment or prevention of delirium, as there is insufficient evidence to support its use, and established guidelines do not include dual orexin receptor antagonists (DORAs) in delirium management algorithms. 1

Current Evidence Base

Guideline-Based Recommendations

The most recent clinical practice guidelines for delirium management do not recommend any specific pharmacological agents for routine delirium treatment:

• Haloperidol and risperidone have no demonstrable benefit in symptomatic management of mild-to-moderate delirium and are not recommended 1
• Atypical antipsychotics (olanzapine, quetiapine, aripiprazole) may offer benefit but evidence remains limited 1
• No pharmacological prevention strategy is recommended based on current evidence 1

Emerging Research on Daridorexant

The evidence for daridorexant specifically is extremely limited and preliminary:

• One feasibility trial (n=11) demonstrated that daridorexant 50 mg given for three nights after heart surgery showed numerically lower delirium symptom burden, but this was not powered for efficacy 2
• One case report described successful management of subsyndromal delirium with daridorexant combined with low-dose quetiapine in a postoperative patient, noting reduced morning drowsiness compared to lemborexant 3
• A scoping review identified 30 reports on DORAs for delirium (mostly suvorexant from Japanese literature), but concluded the evidence remains inconclusive and calls for adequately powered efficacy trials 2

Recommended Management Approach

First-Line: Non-Pharmacological Interventions

Multicomponent non-pharmacological strategies should be the primary approach to delirium prevention and treatment:

• Early mobilization reduces delirium incidence and duration 1, 4
• Sleep optimization through controlling light/noise, clustering care activities, and reducing nighttime stimuli 1, 4
• Cognitive stimulation and reorientation using familiar objects and clocks 1, 4
• Environmental modifications ensuring adequate daytime lighting and reducing sensory deprivation 4

Pharmacological Considerations When Necessary

If pharmacological intervention is required for severe distress, agitation, or safety concerns:

• Dexmedetomidine is preferred for mechanically ventilated patients with agitation precluding extubation 1, 4
• Short-term antipsychotics (haloperidol or atypical agents) may be warranted for patients with significant distress from hallucinations, delusions, or dangerous agitation, but should be discontinued immediately after symptom resolution 1
• Avoid benzodiazepines as they may be a risk factor for developing delirium 1, 4

Address Underlying Causes

Comprehensive assessment of precipitating factors is essential:

• Opioid rotation to fentanyl or methadone for opioid-induced neurotoxicity 1
• Treat hypercalcemia with bisphosphonates (pamidronate or zoledronic acid) 1
• Manage infections, hypomagnesemia, and SIADH according to goals of care 1
• Discontinue implicated medications including anticholinergics and unnecessary sedatives 1

Critical Caveats

Why Daridorexant Cannot Be Recommended

• No guideline support: Major delirium guidelines (ESMO 2018, Society of Critical Care Medicine 2018) do not mention DORAs 1
• Insufficient efficacy data: Only one small feasibility study exists, not powered to demonstrate clinical benefit 2
• Pharmacokinetic concerns: Risk of next-morning sedation must be carefully considered, which could worsen delirium or interfere with rehabilitation 2, 3
• No FDA approval: Daridorexant is approved only for insomnia, not delirium 2

Common Pitfalls to Avoid

• Do not use antipsychotics prophylactically to prevent delirium, as this has no demonstrated benefit 1, 4
• Avoid antipsychotics in patients with QT prolongation or risk factors for torsades de pointes 1, 4
• Do not rely solely on pharmacological interventions without addressing modifiable environmental factors and underlying medical causes 4
• Failure to systematically screen for delirium using validated tools (CAM-ICU, ICDSC) delays intervention 4

Clinical Bottom Line

Until adequately powered randomized controlled trials demonstrate efficacy and safety, daridorexant should not be used for delirium treatment or prevention. 2 Focus instead on evidence-based multicomponent non-pharmacological interventions, identification and treatment of underlying causes, and judicious short-term use of established agents (dexmedetomidine, atypical antipsychotics) only when necessary for severe distress or safety concerns. 1, 4