Daridorexant in patients with insomnia and psychiatric comorbidity: long-term real-world clinical experience

Background

Insomnia is highly prevalent among patients with psychiatric disorders and often becomes chronic. Persistent insomnia is associated with impaired daytime functioning, worsening of psychiatric symptoms, and prolonged use of benzodiazepines or other GABAergic hypnotics, which may lead to tolerance, dependence, cognitive impairment, and increased risk of falls. Long-term management of insomnia in psychiatric populations therefore represents a major clinical challenge.

Daridorexant is a dual orexin receptor antagonist (DORA) that promotes sleep by selectively inhibiting wake-promoting orexin signaling, without direct GABAergic effects. This pharmacological profile may provide advantages in terms of tolerability**¹** and suitability for long-term use**²**. However, real-world evidence in patients with psychiatric comorbidity and prolonged exposure remains limited.

Objectives

The aim of this study was to evaluate the long-term effectiveness, tolerability, and impact on concomitant hypnotic treatment—particularly benzodiazepines—of daridorexant in a real-world psychiatric outpatient population.

Methods

This observational, multicenter, retrospective, descriptive, uncontrolled study was conducted in psychiatric outpatient settings. Adult patients with insomnia and psychiatric comorbidity who received daridorexant for more than six months were included. A total of 34 patients were analyzed.

Collected data included demographic variables, type and duration of insomnia, psychiatric comorbidities, duration and dose of daridorexant treatment, baseline and final Insomnia Severity Index (ISI) scores, self-reported sleep duration, daytime functioning, adverse events, and changes in concomitant hypnotic medication, particularly benzodiazepines. Descriptive statistics were used to summarize the data.

Results

The mean age of the patients was 54 years, and 64.7% were women. Insomnia was predominantly chronic, with a duration exceeding 12 months in most cases. Mixed and sleep-maintenance insomnia were the most frequent subtypes. Psychiatric comorbidity was heterogeneous and included depressive and anxiety disorders, bipolar disorder, personality disorders, attention-deficit/hyperactivity disorder, and substance use disorder.

The mean duration of treatment with daridorexant was 9.18 months (SD 3.67; 95% CI: 7.88–10.48). At baseline, the mean ISI score was 20.4 (SD 2.6; median 20), corresponding to moderate-to-severe insomnia. After treatment, the mean final ISI score decreased to 7.7 (SD 4.1; median 7). No patients had a total ISI score below 15 points at baseline, whereas at the end of follow-up, 90.9% of patients (30/33) achieved an ISI score <15, indicating subclinical or absent insomnia.

Self-reported sleep duration increased from approximately 4–5 hours at baseline to 7–9 hours during follow-up. Improvements in daytime functioning were commonly reported, with no clinically relevant increase in daytime sleepiness.

Among patients receiving benzodiazepines at baseline, 76.2% (16/21) achieved a reduction of at least 50% in benzodiazepine use during daridorexant treatment. Adverse events were infrequent, mild, and did not result in treatment discontinuation.

Conclusions

In routine clinical practice, daridorexant demonstrated sustained long-term effectiveness and good tolerability in patients with insomnia and psychiatric comorbidity. Treatment was associated with marked improvements in insomnia severity, sleep duration, and daytime functioning, as well as a substantial reduction in benzodiazepine use. These findings support daridorexant as a valuable long-term therapeutic option for insomnia in complex psychiatric populations.

References

Mignot E, et al. Lancet Neurol. 2022;21:125–39
Kunz D, et al. CNS Drugs. 2023;37:93–106.