Lemborexant in insomnia patients with psychiatric comorbidities: Real-world experience
Insomnia is commonly comorbid with psychiatric conditions, including depressive and anxiety disorders. This bidirectional relationship highlights the importance of appropriate and comprehensive management to improve patients’ outcomes. In an interview with MIMS Doctor, Dr Hidenobu Suzuki of the Department of Psychiatry, Suzuki Clinic, Tokyo, Japan, shared real-world experience with the use of lemborexant (Dayvigo®, Eisai) for insomnia management in 150 patients with psychiatric comorbidities treated at his clinic.
Insomnia and psychiatric comorbidities: A bidirectional relationship
“More than 90 percent of patients with insomnia have psychiatric comorbidities, including depression, anxiety disorders, and schizophrenia,” said Suzuki. [SAGE Open Med 2021;doi:10.1177/20503121211039098]
“Insomnia often precedes the development of depressive and anxiety disorders, and also contributes to exacerbation or recurrence of their symptoms,” explained Suzuki. “It is also associated with cognitive dysfunction, and sleep-onset symptoms may persist in patients with schizophrenia who are in remission.”
“The close bidirectional relationship between insomnia and psychiatric comorbidities highlights the importance of comprehensive evaluation of sleep, mood and psychotic symptoms for holistic management,” he advised. “Effective management of insomnia may contribute to improved response to treatment of psychiatric comorbidities and, hence, better long-term prognosis.”
Lemborexant for insomnia
“Conventional hypnotics are notorious for their risk of dependence, tolerance and withdrawal symptoms, making downtitration or treatment discontinuation difficult. They are also at risk of causing cognitive dysfunction,” said Suzuki. [J Am Geriatr Soc 2012;60:616-631; Nat Rev Drug Discov 2011;10:685-697; Trends Neurosci 2011;34:188-197] “As a result, patients may be reluctant to use them.”
“Lemborexant, a dual orexin receptor antagonist [DORA], induces physiological sleep and has a low risk of the above issues,” he highlighted. [Nat Med 2007;13:150-155]
In pivotal phase III trials (SUNRISE 1 in 1,006 adults aged ≥55 years, and SUNRISE 2 in 949 adults aged ≥18 years), lemborexant has demonstrated efficacy in sleep onset, maintenance and efficiency, with a favourable safety and tolerability profile. [JAMA Netw Open 2019;2:e1918243; Sleep 2020;43:1-11]
“Lemborexant’s favourable safety and tolerability profile makes it suitable for long-term use and contributes to improved adherence. In addition, its flexible and wide range of dosing [2.5–10 mg] facilitates titration and allows planning of an exit strategy,” said Suzuki.
Lemborexant in patients with psychiatric comorbidities
The SUNRISE 2 trial allowed inclusion of patients with sufficiently treated psychiatric comorbidities, including those concomitantly treated with an antidepressant. [Nierenberg AA, et al, Psych Congress 2020, poster 189]
In a subgroup of 112 patients with a history of depression (concomitant antidepressant use, 51.3 percent and 38.5 percent in the lemborexant 5 mg and 10 mg groups, respectively), lemborexant improved sleep outcomes over 6 months of follow-up. The improvements were at least comparable to those seen in patients without a history of depression, with similar treatment-emergent adverse events (AEs) between the two subgroups, which were mostly of mild or moderate intensity.
Real-world study in Japanese patients
Suzuki and his colleagues conducted a real-world retrospective study on the efficacy of lemborexant in Japanese patients with insomnia (n=150; mean age, 47.8 years; female, 62.0 percent). The patients’ most common psychiatric comorbidity was depression (n=59; 39.3 percent), followed by anxiety (n=53; 35.3 percent), bipolar disorder (n=24; 16.0 percent), dementia (n=12; 8.0 percent), and schizophrenia (n=2; 1.3 percent). The mean duration of illness was 4.2 years. [SAGE Open Med 2021;doi:10.1177/20503121211039098]
At baseline, concomitant antidepressants were used by 35.3 percent of patients (n=53). Concomitant benzodiazepine anxiolytics were used by 29.3 percent of patients (n=44), while concomitant mood stabilizers and antipsychotics were used by 12.0 percent (n=18) and 10.7 percent of patients (n=16), respectively. The average lemborexant dose was 5.9 mg, and follow-up duration was 6 months between July and December 2020.
“The patients’ mean Athens Insomnia Scale [AIS] score significantly improved from 6.6 at baseline to 3.9 after 6 months of treatment [p<0.01]. The mean Clinical Global Impressions–Improvement [CGI-I] score was 3.2,” Suzuki reported.
“Twenty-one patients stopped taking lemborexant due to improved insomnia,” he continued. “Treatment continuation rate at 6 months among the remaining 129 patients was 86.7 percent.” (Figure)
Among 13 of 129 patients who discontinued lemborexant treatment after 6 months, the most common reason was sleepiness (n=5), followed by lack of efficacy (n=4), patients’ decision (n=2), fatigue (n=1), and nightmares (n=1). All AEs were mild, transient, and resolved after treatment discontinuation.
“These results support the efficacy and safety of lemborexant in insomnia treatment in real-world clinical practice,” Suzuki commented.
Practical advice on lemborexant use
“In patients with insomnia and mild psychiatric comorbidities, I would start lemborexant at 5 mg nocte, or 2.5 mg nocte for the elderly. For those with moderate psychiatric comorbidities, I would add lemborexant 5 mg, or 2.5 mg for the elderly, to the patients’ existing antidepressants such as selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors, while benzodiazepine anxiolytics may be prescribed temporarily, if needed,” said Suzuki. “Patients are followed up every 2 weeks to evaluate treatment efficacy, tolerability and adherence, based on which doses are titrated, while other concomitant insomnia medications are downtitrated until discontinued.”
Expectation setting and patient education are important. “We should explain to patients that the sensation of falling asleep with lemborexant may differ from that with previously used insomnia medications. Thus, some patients may perceive a temporary worsening of insomnia symptoms,” Suzuki advised.
“It is also important to mitigate patients’ concerns and anxiety related to sleep,” he continued. “In addition to sleep hygiene education, we specifically advise patients not to worry about sleep duration as long as their sleep pattern does not adversely affect their social or professional life.”