Lemborexant-Associated Nightmares: Clinical Management and Guidelines

Understanding Drug-Induced Nightmares

The American Academy of Sleep Medicine guidelines state that nightmares can be induced by drugs affecting norepinephrine, serotonin, and dopamine neurotransmitters, as well as by withdrawal of REM-suppressing agents and drugs affecting GABA and acetylcholine, with the strength of evidence being based on clinical observations and case reports 1
Whether nightmares induced by drugs have long-term sequelae even after removing the offending agent is not known, and it is unclear if these drug-induced nightmares share a common pathophysiology with other nightmare types, highlighting the need for further research 1

When a patient on lemborexant reports nightmares, first confirm the temporal relationship between medication initiation and nightmare onset, as recommended by the American Academy of Sleep Medicine guidelines 1
Key diagnostic criteria to assess include recurrent awakenings from sleep with recall of intensely disturbing dream content involving fear, anxiety, anger, sadness, or disgust, with full alertness on awakening and immediate and clear recall, as well as delayed return to sleep after episodes or occurrence in the latter half of the sleep period 1

Rule out alternative causes before attributing nightmares solely to lemborexant, including underlying psychiatric conditions, other medications affecting neurotransmitter systems, and recent trauma or significant life stressors, as suggested by the American Academy of Sleep Medicine guidelines 1
Sleep deprivation or irregular sleep-wake schedules can also intensify nightmares, according to Praxis Medical Insights 2

If nightmares are clearly temporally related to lemborexant and no other cause is identified, consider dose reduction first, and if nightmares persist or are intolerable, discontinue lemborexant, as there is no evidence supporting spontaneous resolution with continued use, as stated by the American Academy of Sleep Medicine guidelines 1