The dual orexin receptor antagonist lemborexant (Dayvigo) consistently helped patients with insomnia, including those with a history of depression, according to a phase III randomized study and a post-hoc analysis.
Using the self-report Patient Global Impression-Insomnia scale, more than 70% of participants said that 5-mg or 10-mg lemborexant helped them sleep at night at months 9 and 12 of the study, reported Margaret Moline, PhD, of Eisai in Woodcliff Lake, New Jersey, and colleagues in a poster at the Psych Congress, held virtually and in San Antonio.
More than 75% of patients also noted that the medication shortened the time it took to fall asleep, and more than 60% said it increased their total sleep time at months 9 and 12, the researchers added.
"The majority of subjects receiving lemborexant reported a positive medication effect that was sustained up to 12 months," Moline said during her presentation. "Since ratings of the drug being 'too weak' were also stable up to 12 months, this supports the view that tolerance to lemborexant did not occur."
Lemborexant became available last year after being approved by the FDA in late 2019 to treat insomnia with sleep onset or sleep maintenance difficulties.
Patients tolerated the drug well, with less than 10% in either dosage group reporting treatment-emergent adverse events (TEAEs) that led to study discontinuation over 12 months of treatment. Of the patients receiving 5-mg lemborexant, 72% experienced any TEAE, as did 69.7% of participants receiving the 10-mg dose. The most common among these events (>10%) were nasopharyngitis (13.7% and 13.4%, respectively), somnolence (9.6% and 14.3%), and headaches (11.1% and 9.2%).
All 949 study participants in this double-blind 12-month study were over the age of 18, met the DSM-5 criteria for insomnia disorder, had an Insomnia Severity Index (ISI) score of 15 or higher, and did not have any other sleep disorder diagnoses.
The first 6 months of the study were placebo-controlled, with 318 patients in the placebo group, and the next 6 months focused solely on those continuing their lemborexant dosages of either 5 mg (316 patients) or 10 mg (315 patients).
In another poster, Moline and colleagues presented a post-hoc analysis of the same study, highlighting how lemborexant affected sleep outcomes and insomnia severity in participants with a history of depression. Of the 949 patients in the full study, 112 had a history of depression: 34 in the placebo group, 39 in the 5-mg group, and 39 in the 10-mg group. They found that the drug was beneficial for these patients in measures of sleep onset, sleep maintenance, insomnia severity, and the impact of insomnia on daytime functioning according to the ISI questionnaire.
For example, median decreases from baseline in subjective sleep onset latency (sSOL) at the 6-month mark were significantly greater with the 10-mg dose compared with the placebo group, and numerically greater across all time points. When comparing the 5-mg group with the placebo group, decreases in sSOL were numerically greater during the first 7 nights and at the end of months 1, 5, and 6.
Decreases from baseline in sSOL with lemborexant 10 mg at months 1 to 6 were significantly greater (P<0.05 for all) for those with a history of depression compared with those without. Across all time points, the median change from baseline was approximately 9 to 17 minutes greater in participants with depression treated with the 10-mg dose than those without history of depression.
Least squares mean increases in subjective sleep efficiency (sSE) from baseline were numerically greater with lemborexant 5 mg compared with the placebo group during the first 7 nights and at the end of month 1 and months 3 to 6; in the 10-mg group, sSE increases from baseline were numerically greater across 6 months of treatment. No significant differences were found, however, in the decreases from baseline of subjective wake after sleep onset for either dosage group and the placebo group throughout the 6 months.
"The results of this subgroup analysis support the potential use of lemborexant in patients with insomnia and a history of depression," Moline concluded.
This research was supported by Eisai.
Several authors disclosed receiving consulting fees from various pharmaceutical companies.