Do nightmares caused by Lemborexant (lemboorexant, an orexin receptor antagonist) in an adult patient with no prior psychiatric history subside with time?

Lemborexant-Associated Nightmares: Natural History and Management

Nightmares caused by lemborexant occur in 2-5% of patients at the 10 mg dose, but there is no evidence that these drug-induced nightmares spontaneously resolve with continued use—discontinuation of the offending agent is the appropriate management strategy. 1

Understanding Drug-Induced Nightmares

The American Academy of Sleep Medicine guidelines explicitly 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. 2 Critically, 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. 2

Lemborexant-Specific Evidence

Incidence and Dose-Relationship

• Nightmares affect approximately 2-5% of patients taking lemborexant 10 mg, with adverse effects being higher at this dose compared to the 5 mg dose. 1
• The 10 mg dose shows roughly similar nightmare rates to suvorexant 40 mg (though the recommended suvorexant dose is 20 mg). 1
• In clinical trials, somnolence occurred in about 10% of patients at 10 mg, while headache and nightmares affected 2-5%. 1

Long-Term Safety Data

• Long-term studies extending up to 12 months show that most treatment-emergent adverse events with lemborexant are mild to moderate, with the most common being nasopharyngitis, somnolence, and headache—but these studies do not specifically address whether nightmares persist, worsen, or resolve with continued treatment. 3
• There is no evidence of tolerance development or withdrawal effects on discontinuation. 1

Clinical Management Algorithm

Immediate Assessment

When a patient on lemborexant reports nightmares, first confirm the temporal relationship between medication initiation and nightmare onset. 2 Key diagnostic criteria to assess include:

• Recurrent awakenings from sleep with recall of intensely disturbing dream content involving fear, anxiety, anger, sadness, or disgust 2
• Full alertness on awakening with immediate and clear recall 2
• Delayed return to sleep after episodes or occurrence in the latter half of the sleep period 2

Differential Diagnosis

Rule out alternative causes before attributing nightmares solely to lemborexant:

• Underlying psychiatric conditions (PTSD, depression, anxiety, borderline personality disorder, schizophrenia-spectrum disorders) 2
• Other medications affecting neurotransmitter systems 2
• Recent trauma or significant life stressors 2
• Sleep deprivation or irregular sleep-wake schedules, which can intensify nightmares 4

Management Decision Points

If nightmares are clearly temporally related to lemborexant and no other cause is identified:

1. Consider dose reduction first: Reduce from 10 mg to 5 mg, as adverse effects including nightmares are dose-dependent 1, 5

2. If nightmares persist at 5 mg or are intolerable: Discontinue lemborexant, as there is no evidence supporting spontaneous resolution with continued use 2

3. Monitor for withdrawal: Although lemborexant shows no evidence of withdrawal effects or rebound insomnia, monitor sleep patterns for 1-2 weeks post-discontinuation 3

Important Caveats

Lack of Resolution Data

The critical gap in the evidence is that no studies specifically track whether lemborexant-induced nightmares resolve with continued treatment. 2 The American Academy of Sleep Medicine guidelines acknowledge this uncertainty for all drug-induced nightmares, stating explicitly that whether these nightmares have long-term sequelae after removing the offending agent is unknown. 2

Other Concerning Adverse Effects

Beyond nightmares, lemborexant can cause sleep paralysis, hypnagogic/hypnopompic hallucinations, cataplexy-like symptoms, complex sleep behaviors, and emergence of depression or suicidal ideation—all of which warrant immediate clinical attention and potential discontinuation. 1

Monitoring Requirements

Until efficacy and safety are adequately investigated in patients with major mental disorders, clinicians need to monitor patient experience closely, particularly for psychiatric adverse effects. 1