Pharmacologic Effectiveness of Dual Orexin Receptor Antagonists Compared to Atypical Antidepressants for Adult-Onset Primary Insomnia

Faculty Sponsor

Jana Stedman, PA-C




Physician Assistant Program

Presentation Type

Poster Presentation

Symposium Date

Summer 7-26-2023



Objectives: The objective of this research was to identify whether dual orexin receptor antagonist (DORA) medications are more effective than atypical antidepressants in the treatment of adult onset primary insomnia. Subjective sleep data and objective polysomnography (PSG) measures of sleep (sleep efficiency [SE], latency to persistent sleep [LPS] and wake after sleep onset [WASO]) were used to measure treatment efficiency.

Methods: Data from 4 randomized, double-blinded, placebo-controlled studies and 7 systematic reviews with network meta-analyses were collected to identify the effectiveness of DORA medications and antidepressants in treating primary insomnia in adults aged 18-64. Primary outcomes in this research included sleep efficiency (measured subjectively with sleep diaries and objectively with PSG data), treatment discontinuation due to medication side effects, and safety measurements (number of medication-induced adverse events overall).

Results: All primary outcomes of subjective sleep data, total sleep time (TST), latency to persistent sleep (LPS), and wake after sleep onset (WASO) were all significantly improved among subjects receiving DORA therapy versus placebo across 3 of the placebo-controlled studies. DORA medications also yielded higher risks of medication induced adverse effects including somnolence, fatigue, and dry mouth.

Conclusions: DORA medications showed significant improvement of objective and subjective sleep measurements when compared to placebo management. Atypical antidepressants did not significantly improve subjective and PSG sleep efficiency when compared to placebo and cognitive behavioral therapy (CBT) across all studies.

Keywords: atypical antidepressants, Suvorexant, Lemborexant, dual orexin receptor antagonists, cognitive behavioral therapy, Doxepin, primary insomnia.

Biographical Information about Author(s)

Tyler Bush has an interest in Internal Medicine and plans on working in Primary Care following graduation. He has participated as a member of professional organizations such as the American Academy of Physician Associates (AAPA), as well as the Valparaiso University Physician Assistant Student Society (VUPASS) working as the class treasurer during didactic year. Tyler has recently represented Valparaiso University at the 2023 national AAPA conference as a member of the Challenge Bowl team. He will be presenting on “Pharmacologic Effectiveness of Dual Orexin Receptor Antagonists in the Management of Adult-onset Primary Insomnia” after developing an interest in alternative methods of insomnia management following his behavioral health rotation.

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