Management of Subsyndromal Delirium With Daridorexant and Quetiapine: A Case Report

Subsyndromal delirium (SSD), characterized by subthreshold symptoms of delirium such as disturbances in attention and cognition, is prevalent in the intensive care unit (ICU) and is associated with prolonged hospitalization and delayed functional recovery. However, evidence-based treatment guidelines remain limited. Here, we present a postoperative patient with SSD successfully managed with daridorexant and quetiapine. A 76-year-old man with a history of pharyngeal cancer and tracheostomy developed acute insomnia in the ICU following surgery for esophageal cancer. Lemborexant was initiated on postoperative day (POD) 6 and titrated to the maximum dose of 10 mg on POD 8, but it caused morning drowsiness that interfered with participation in rehabilitation. On POD 10, he was referred to the Consultation-Liaison team. Based on his disrupted sleep-wake cycle and fluctuating mood following dyspnea due to aspiration pneumonia, he was diagnosed with SSD (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR)) with comorbid acute insomnia. We initiated daridorexant on POD 10 and increased the dose to 50 mg on POD 12, leading to reduced morning drowsiness and improved sleep initiation. Although these symptoms improved, fluctuating mood and poor appetite persisted slightly. Low-dose quetiapine (12.5 mg) was subsequently added, resulting in stabilization of psychiatric symptoms and steady rehabilitation progress. He was discharged on POD 31, and all psychotropic medications were successfully discontinued at discharge. Conclusions: Daridorexant, a dual orexin receptor antagonist (DORA) with a shorter half-life, appeared effective in reducing morning drowsiness. As the use of short-acting benzodiazepines has a potential risk of inducing delirium, the combination of daridorexant and low-dose quetiapine may present a therapeutic option for managing SSD with delayed awakening in the postoperative setting.