Real-world experience with daridorexant for insomnia in adults with intellectual disabilities: a retrospective single-centre case series

Abstract

Chronic insomnia is common in adults with intellectual disabilities, yet evidence to guide pharmacological management is limited. We report a real-world case series of five adults with intellectual disabilities and multimorbidity treated with daridorexant, a dual orexin receptor antagonist approved in Europe for insomnia. Daridorexant was associated with marked improvements in sleep quality and quantity, despite complex comorbid sleep, physical, mental and neurodevelopmental disorders. Subject to the limitations of a small, uncontrolled case series, these gains were associated with other reported improvements, including a reduction in challenging behaviours, improved daytime functioning and substantial alleviation of parent and carer burden.

PLAIN LANGUAGE SUMMARY

Why is this case series being reported?

Many people with intellectual disabilities have long-term insomnia, but there is only limited evidence to guide which medicines might work best for them. Treating the insomnia is often complicated by the fact that many of these individuals have other sleep problems (such as obstructive sleep apnoea) as well as physical, mental, or neurodevelopmental conditions such as epilepsy, psychosis, autism, or attention-deficit hyperactivity disorder (ADHD). Since people with intellectual disabilities are usually left out of clinical trials, real-world clinical experience becomes especially important. This case series describes five adults (four of whom were non-verbal) with intellectual disabilities and multiple other health conditions who were treated with daridorexant at a Sleep Disorders Centre in the United Kingdom.

What is daridorexant and how does it work?

Daridorexant belongs to a newer group of sleep medicines called orexin receptor antagonists. These medicines work by blocking signals in the brain that keep people awake, helping to reduce overactive wakefulness. In clinical trials of adults with insomnia, daridorexant improved their nighttime sleep and their ability to function during the day compared with placebo. In studies lasting up to 12 months, daridorexant was found to be generally safe and well tolerated. People who stopped taking it showed no signs of dependence, tolerance or rebound insomnia.

What did the results show?

All five patients in this case series had major improvements in both the quality and amount of their sleep. They were able to sleep through the night or for long stretches at a time (such as 6 hours), regardless of their other health conditions. Along with better nighttime sleep and no signs of excessive daytime sleepiness, carers noticed a number of additional benefits. These included fewer challenging behaviours (such as aggression), better mood and daytime functioning, and a significant reduction in stress and workload for parents and carers.

Three patients had been taking daridorexant continuously for 6, 9 and 14 months at the time that the case series was prepared, and the benefits had not worn off. No side effects or safety concerns were identified. When carers were asked specifically about next-day sleepiness, balance problems, falls or unusual night-time behaviours, none were reported.

Takeaway message

Although this is a small report from a single sleep centre, it is the first to describe the use of daridorexant in people with intellectual disabilities. We believe that, when combined with behavioural sleep advice (sometimes referred to as ‘sleep hygiene’), daridorexant offers clinicians a useful option for managing long-term insomnia in this group of patients.

Introduction

Insomnia is more common in adults with intellectual disabilities relative to the general population and is typically chronic, complex and difficult to control.1,2 Its management is complicated by the frequent presence and contribution of co-occurring sleep disorders (e.g. obstructive sleep apnoea (OSA)),3 and various comorbid physical (e.g. epilepsy), mental (e.g. psychosis) and neurodevelopmental (e.g. autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD)) disorders.1,4,5 Chronic insomnia can have a profoundly negative impact on the physical and mental health and quality of life of affected individuals and their family or caregivers, increasing both the burden and cost of care. Associated consequences include increased risk of behavioural problems, impaired daily functioning, mood disturbances and exacerbation of comorbid conditions.2,3

Despite a clear need for guidance in treating chronic insomnia in individuals with intellectual disabilities, their exclusion from clinical research means that the evidence base is limited.2 In the absence of sleep medicine guidelines specific to this patient group, management recommendations tend to follow those for the general population.1,2 In the UK and Europe,6,7 first-line treatment for chronic insomnia is cognitive behavioural therapy for insomnia (CBTi), of which some aspects may be useful for individuals with intellectual disabilities.1,2 Pharmacological management of chronic insomnia consists mainly of melatonin and melatonin receptor agonists, benzodiazepines and hypnotic benzodiazepine receptor agonists, low-dose sedating antidepressants, and orexin receptor antagonists.7,8

No published data are currently available on the use of daridorexant in adults with intellectual disabilities. Daridorexant is an orally administered dual orexin type 1 and type 2 receptor antagonist approved in Europe for the treatment of adult patients with insomnia characterized by symptoms present for at least 3 months and considerable impact on daytime functioning.9 Daridorexant selectively blocks the activation of orexin receptors, thereby directly targeting the mechanism that controls overactive wakefulness and providing an alternative to conventional positive allosteric gamma-aminobutyric acid (GABA)-A receptor modulators.10 Pivotal 12-week phase III clinical trials in adults with insomnia disorder demonstrated that daridorexant improved sleep and daytime functioning whilst maintaining a favourable safety profile.11 In treatment for up to 12 months, daridorexant was generally safe and well tolerated with no physical signs of dependency, tolerance or rebound insomnia after its discontinuation.12 Meta-analyses concluded that the overall risk of adverse events with daridorexant was comparable to that of placebo.13,14 Currently, three dual orexin receptor antagonists are approved worldwide for insomnia; amongst these, daridorexant is the only agent authorized for use in Europe. Daridorexant is characterized by relatively rapid absorption (t_max of 1–2 hours) and a shorter elimination half-life (approximately 8 hours) than suvorexant or lemborexant, which may limit next-morning residual effects.15

Guidance issued by the UK’s National Institute for Health and Care Excellence (NICE) recommends daridorexant for treating insomnia in adults with symptoms lasting for 3 nights or more per week for at least 3 months, and whose daytime functioning is considerably affected. Daridorexant is to be prescribed if CBTi has been tried but is unsuccessful, is not available or is unsuitable.16 However, these recommendations are based on studies conducted in neurotypical patients treated under strictly controlled conditions. To be relevant to daily practice in the sleep disorders field, it is necessary to know whether daridorexant is effective in unselected, heterogeneous adults, including those with intellectual disabilities, a group characterized by multimorbidity and other vulnerabilities.

This article describes the use of daridorexant in five illustrative clinical cases of adults with intellectual disabilities and multiple comorbidities, thus initiating an understanding of its real-world effectiveness and safety for the management of chronic insomnia in this patient group.

Patients and methods

A structured search of the literature (PubMed and Embase) using search terms “daridorexant”, “orexin” and “intellectual disability”, and restricted to English-language publications up to March 2026, found no published reports of daridorexant use specifically in adults with intellectual disabilities.

The author retrospectively reviewed and compiled clinical cases of all consecutive adult patients with intellectual disabilities treated with daridorexant for chronic insomnia at the Sleep Disorders Centre at Guy’s and St Thomas’ NHS Foundation Trust between March 2024 and March 2025; no additional adult patients with intellectual disabilities received daridorexant for chronic insomnia at this centre during this period. Inclusion criteria were adults aged ≥18 years with established intellectual disability and clinician-diagnosed chronic insomnia (as per International Classification of Sleep Disorders-3 guidelines). Given the retrospective nature of the study and non-verbal status of most patients, only narrative caregiver-reported outcomes could be captured reliably. To our knowledge, no validated insomnia scales exist for this population.2 The similarity in narrative descriptions of each patient is intentional to facilitate comparison across cases. Table 1 provides a summary of the clinical cases.

Table 1.

Clinical characteristics and sleep outcomes in five adults with intellectual disabilities treated with daridorexant.

Case	Age (years)/ Sex (M:F)	ID severity	Sleep disorder(s)	Main co-morbidities	Daridorexant	Outcomes
1	29 / M	Severe (non-verbal)	Insomnia	ASD Psychosis (under MHID services; prescribed lurasidone 18.5 mg once daily)	25 mg (from April 2025)	Pre: – Waking at midnight, fragmented sleep until 2:30 AM, then fully awake until 8 AM – When awake, needed to have his mother and brother with him – Sleepy during the day; unable to engage in college activities; ‘more emotional’; increased challenging behaviours (aggression) – Family exhausted
						Post: – Sleeping through the night except for one awakening to use the bathroom – No residual daytime sleepiness; mood improved; challenging behaviours markedly reduced and were no longer a prominent concern – No side-effects – Caregivers reported ‘striking’ improvement in sleep and behaviour – Discharged back to MHID services
2	60 / M	Severe (non-verbal)	Insomnia	ASD Psychosis (prescribed aripiprazole) Migraine	25 mg (from April 2025) combined with sleep compression advice	Pre: – Very delayed sleep initiation – Going into other residents’ rooms, making noise, banging furniture – Accommodation at risk; MHID services stuck for solutions – Naps for 2 hours during the day
						Post: – Sleeping from 10 PM to 05:30 AM – Challenging behaviours markedly reduced and no longer a major issue in the residential setting – No residual daytime sleepiness – Accommodation no longer considered at risk – No apparent side-effects – Carers reported that improvements in sleep and behaviour exceeded their expectations
3	24 / F	Severe (non-verbal)	Insomnia	Ring chromosome 18 disorder Bone anchored hearing aid Surgically corrected cardiac and palate defects	50 mg (started on 25 mg in March 2024), combined with trazodone 200 mg once nightly	Pre: – Nights of no sleep (up to 96 hours in a row); followed by rebound excessive sleep – Other nights of very little and fragmented sleep, with excessive daytime sleepiness – Unable to engage in college activities; mood variable depending on sleep – Parents had not had a proper night’s sleep in years – Social services recommending supported residential accommodation, which the family does not want
						Post: – For the past ~14 months, has been sleeping for 6.5 hours consistently at night – No problematic daytime sleepiness – Able to engage in college – Mood stable – No apparent side-effects – Parents described the change in her sleep and functioning after years of severe insomnia as life-changing
4	19 / M	Severe (non-verbal)	Insomnia OSAS	ADHD General epilepsy with SCN1A mutation (includes nocturnal seizures). Seizures are treatment-resistant and patient at risk of SUDEP	50 mg (25 mg started in January 2025)	Pre: – Very poor nocturnal sleep – Uncontrolled OSA triggering seizures – Exhausted the next day and/or shows increase in challenging behaviours (aggression, headbutting) – Seizures increase after poor sleep – Family at the end of their tether – Referred by community paediatrics as patient facing residential care (family – “we don’t want this, if only we could fix his sleep”) – All involved in care are concerned about the increasing risk of SUDEP
						Post: – Sleeping 6–8 hours per night – CPAP concordance improved (aided by night-time carers) – Seizures have decreased; reduced risk of SUDEP – Challenging behaviours markedly reduced – Can attend a daytime college – No apparent side-effects – Parents described the combined impact on sleep, seizures and daily life as life-changing
5	47/ F	Mild (verbal)	CRSD not otherwise specified Insomnia	1. Smith–Magenis syndrome 2. Hydrocephalus 3. Hypomania with psychosis	50 mg (since September 2024); in conjunction with trazodone 150 mg once nightly and ½ a melatonin 2 mg tablet at 7 AM	Pre: – Previous community MHID services’ efforts to treat CRSD were unsuccessful – Some improvement with trazodone (night) and low-dose melatonin (morning) but did not adequately treat co-morbid insomnia – Bed at 11 PM; delayed sleep latency of 1 hour; waking at 3 AM for another hour; final awakening at 5 AM. – Engages in very loud shouting after waking in the night – Sleeping during the day – Increased psychotic symptoms - openly verbalising to dead relatives
						Post: – Sleeping 5–6 hours in one block – Falling asleep faster – No problematic excessive daytime sleepiness – Nighttime shouting resolved – Psychotic symptoms decreased without change in olanzapine dose – No apparent side-effects – Carers reported that her sleep and associated behaviours were much better controlled than before treatment

ADHD, attention deficit hyperactivity disorder; ASD, autism spectrum disorder; CPAP, continuous positive airway pressure; CRSD, circadian rhythm sleep wake disorder; ID, intellectual disability; MHID, Mental Health in Intellectual Disabilities; OSA, obstructive sleep apnoea; OSAS, obstructive sleep apnoea syndrome; SUDEP, sudden unexpected death in epilepsy.

Case review and compilation was performed in January 2026. In accordance with Guy’s and St. Thomas’ NHS Foundation Trust policies on case series and the UK Health Research Authority Guidance, this retrospective series of fully de-identified cases did not require formal research ethics committee approval nor individual patient/carer consent.

Case studies

Case 1

A 29-year-old male with severe (non-verbal) intellectual disability was referred to our centre with chronic insomnia. Main comorbidities were ASD and psychosis, for which he was under Mental Health and Intellectual Disability (MHID) services and prescribed lurasidone 18.5 mg once daily (unchanged during daridorexant treatment). Previously trialled unsuccessful sleep treatments included modified-release melatonin, diazepam, clonazepam and doxepin.

Prior to referral, the patient was waking at midnight with fragmented sleep until 2:30 AM, then fully awake until 8 AM. When awake, he needed to have his mother and brother with him. Daytime sleepiness interfered with his ability to engage in college activities. He was becoming more emotional, with increasing episodes of challenging behaviours such as aggression. His family was exhausted.

In April 2025, he began treatment with daridorexant 25 mg once nightly. Within approximately 4 weeks, caregivers reported initial consolidation of his nocturnal sleep with only a single brief awakening. By 2 months of treatment, these improvements were well established, with resolution of his daytime sleepiness, and were maintained until he was discharged back to MHID services. He had no residual daytime sleepiness, his mood improved and the challenging behaviours abated. No side-effects were reported. His mother commented that she could hardly believe the improvement.

Case 2

A 60-year-old male with severe (non-verbal) intellectual disability was referred to our centre with chronic insomnia. Main comorbidities were ASD, psychosis (prescribed aripiprazole 15 mg once daily in the morning, unchanged during daridorexant treatment), and migraine. Previously trialled unsuccessful sleep treatments included melatonin, promethazine 75 mg and clonazepam.

Before referral, the patient had delayed sleep initiation. He would wander into other residents’ rooms, making noise and banging furniture. He napped for around 2 hours during the day. As his residential accommodation was at risk, MHID services were uncertain as to how to proceed.

In April 2025, he began treatment with daridorexant 25 mg once nightly, together with sleep restriction advice: staff were asked to reduce his daytime napping and to limit his time in bed at night to approximately 6 hours (from 23:00 to 05:00), with medication taken within 30 minutes of bedtime.

After 2 months’ treatment with daridorexant, the patient was sleeping from 10 PM to 05:30 AM. Caregivers reported a marked reduction in challenging behaviours and perceived an improvement in daytime sleepiness. His accommodation was no longer considered at risk. Carers commented that they should not have waited so long to present to the sleep disorders clinic and were genuinely surprised to discover that the patient could actually sleep. No side-effects were reported with daridorexant.

Case 3

A 24-year-old female with severe (non-verbal) intellectual disability was referred to the sleep disorders clinic for chronic insomnia. Main comorbidities were ring chromosome 18 disorder, bone anchored hearing aid, and surgically corrected cardiac and palate defects. The patient had previously trialled numerous sleep treatments without success, including promethazine, melatonin (Circadin) up to 6 mg, zopiclone 7.5 mg, mirtazapine 15 mg, a sleep-focused psychological intervention under children’s services (as reported by her mother), clonazepam 0.5 mg (a mechanical fall during the trial resulted in temporary wheelchair use), quetiapine 50 mg, biomelatonin 3 mg, doxepin 10 mg, pregabalin 300 mg/olanzapine 2.5 mg, zolpidem 5 mg, chlorphenamine (Piriton), chloral hydrate 1.6 g, sertraline (caused bruising and epistaxis), and trazodone 200 mg (ineffective as monotherapy).

Prior to referral, the patient experienced nights of no sleep (up to 96 hours in a row), followed by rebound excessive sleep, and other nights of little and fragmented sleep. She had excessive daytime sleepiness and was unable to engage in college activities. Her mood was highly variable, depending on sleep. Her parents reported a long-term negative impact on their own sleep. Social services were recommending that the patient be placed in supported residential accommodation, which the family did not want.

In March 2024, she began treatment with daridorexant, initially at a dose of 25 mg once nightly for 2 weeks, during which no clear improvement was observed but the medication was well tolerated. The dose was escalated to 50 mg once nightly, in combination with trazodone 200 mg once nightly.

Since beginning treatment with daridorexant 50 mg approximately 14 months ago, the patient has been sleeping consistently for 6.5 hours at night, has no daytime sleepiness and is able to engage at college. Her mood is stable. She has no apparent side-effects. Her parents report a marked and sustained improvement and continued surprise at the persistence of the therapeutic effect. Although they are now able to sleep, they describe being profoundly affected by the period preceding the initiation of daridorexant.

Case 4

A 19-year-old male with severe (non-verbal) intellectual disability was referred to the sleep disorders clinic for chronic insomnia and OSA (apnoea–hypopnoea index 16–34 events/hour). Main comorbidities were ADHD and general epilepsy (with a SCN1A mutation), including nocturnal seizures. Seizures were uncontrolled with sodium valproate/lamotrigine, and the patient was at risk of sudden unexpected death in epilepsy (SUDEP). Previous unsuccessful sleep treatments included melatonin up to 10 mg, promethazine up to 50 mg and doxepin up to 9 mg.

Before referral, the patient had very poor nocturnal sleep, with uncontrolled OSA triggering seizures. His seizure rate increased after poor sleep. He would typically be exhausted the next day and showed an increase in challenging behaviours (aggression, headbutting). His family was at the end of their tether. He was referred to the sleep disorders clinic by community paediatrics as he was facing residential care, which the family did not want (‘if only we could fix his sleep’). Everyone involved in his care was concerned about the increasing risk of SUDEP.

In January 2025, he began treatment with daridorexant 25 mg once nightly. After approximately 4 weeks at 25 mg, caregivers reported possible early improvement in sleep, and the medication was well tolerated; the dose was increased to 50 mg once nightly. Sodium valproate/lamotrigine remained unchanged throughout treatment. Within about 1 week of increasing to 50 mg, caregivers reported that he was sleeping 6–8 hours per night.

After 6 months’ treatment with daridorexant, the patient continued to sleep 6–8 hours per night. Aided by night-time carers who ensured that he wore his mask, caregivers reported that his continuous positive airway pressure (CPAP) use had improved and that he was much more accepting of the mask. His seizure rate decreased for the first time, potentially reducing the risk of SUDEP. His challenging behaviours had markedly reduced, and he was able to attend a daytime college. His parents described the outcome as life-changing. No side-effects of treatment were reported.

Case 5

A 47-year-old female with mild (verbal) intellectual disability was referred to the sleep disorders clinic for circadian rhythm sleep–wake disorder (CRSD), not otherwise specified, and insomnia. Main comorbidities were Smith–Magenis syndrome, hydrocephalus, and hypomania with psychosis (prescribed olanzapine 15 mg, unchanged during treatment). Previous unsuccessful sleep treatments included cetirizine, clonazepam, hydroxyzine, lorazepam, haloperidol and propranolol.

Before referral, community MHID services efforts to treat CRSD had been unsuccessful. Initial prescription of trazodone and low-dose melatonin brought some improvement but did not adequately control the comorbid insomnia. After going to bed at 11 PM, she had a delayed sleep latency of about 1 hour, waking at 3 AM for approximately another hour, with a final awakening at 5 AM. Upon waking in the night, she engaged in loud shouting, which led to a special annex having to be built to separate her from the other residents. She was sleeping during the day and openly verbalising to deceased relatives, consistent with increased psychotic symptoms.

At the time of referral, she was taking trazodone 200 mg once nightly and low-dose melatonin (Circadin 2 mg, half a tablet) at 7 AM as a chronobiotic. In September 2024, she began treatment with daridorexant 25 mg once nightly. After 1 week at 25 mg, the medication was well tolerated and the dose was increased to 50 mg once nightly, in conjunction with ongoing trazodone and morning melatonin at the same doses.

Approximately 1 month after increasing daridorexant to 50 mg, her carer reported that she was sleeping much better, with sleep consolidated into a 5–6-hour nocturnal block, and that daridorexant was well tolerated with no obvious side-effects apart from mild morning drowsiness. In view of this improvement, trazodone was reduced from 200 mg to 150 mg once nightly, whilst morning melatonin and olanzapine 15 mg were continued unchanged.

After 9 months’ treatment with daridorexant 50 mg once nightly, the patient was able to fall asleep faster and was consistently sleeping for 5–6 hours in one block. She had no problematic excessive daytime sleepiness. She no longer shouted during the night. Psychotic symptoms decreased without any change to the olanzapine 15 mg dose, and she had no apparent side-effects from daridorexant. Carers considered her sleep and associated behaviours to be much better controlled than before treatment.

Discussion

This collection of clinical experience with daridorexant for chronic insomnia in five adults with intellectual disabilities managed at the Sleep Disorders Centre at Guy’s and St Thomas’ NHS Foundation Trust provides a first-of-its-kind real-world account of its use, tolerability and potential benefits in this challenging-to-treat patient group. Consistent with the clinical literature, the cases clearly highlight substantial inter-individual complexity in terms of co-occurring sleep disorders, comorbid conditions and treatment resistance.1–3,5 Despite such heterogeneity, daridorexant was associated with subjective improvements in each patient’s insomnia, with caregivers reporting better quality and quantity of nocturnal sleep accompanied by a reduction in excessive daytime sleepiness. Improved sleep was also associated with a reduction in challenging behaviours and psychotic symptoms, as well as improvements in mood and daily functioning. Daridorexant was well tolerated with no apparent side-effects observed in any patient. No adverse effects were reported when carers were systematically asked at follow-up consultations about next day sedation, balance problems, falls or unusual nocturnal behaviours. Alleviation of insomnia symptoms appeared to correlate with stabilisation of care arrangements in three patients, including a reduced risk of losing existing supported accommodation and a diminished perceived need for residential placement where this was against parents’ wishes. Not least, successful treatment of insomnia relieved carer burden by allowing parents to sleep. Collectively, the results emphasize the importance of normalized sleep to all aspects of functioning and quality of life in adults with intellectual disabilities and their carers. Although these uncontrolled observations in a small, selected cohort cannot establish causality, they are consistent with clinical trial data and clinical expectations of daridorexant.

Specific sleep disorders can cluster around comorbid neurodevelopmental disorders as well as genetic syndromes or disorders.17 Amongst the five cases described in this series, three had comorbid ASD or ADHD, three had comorbid psychosis, and three had genetic conditions. Ring chromosome 18 disorder is a rare autosomal anomaly characterized by global developmental delay and intellectual disability, microcephaly, hypotonia, and skeletal abnormalities such as dysmorphic facial features.18 Case 3 was exceptionally challenging given the severity of her insomnia (no sleep reported for up to 96 hours in a row) and extreme treatment resistance (previous unsuccessful trials of 15 medications for sleep). At the time of case compilation, she had been receiving daridorexant continuously for 14 months and was sleeping 6.5 hours at night. Case 4 had insomnia and co-occurring OSA which triggered his seizures (comorbid general epilepsy with SCN1A mutation). Although CPAP is the first-line treatment for OSA, it is often deemed unfeasible for use in individuals with intellectual disability on the basis that it would not be tolerated.3,19 In this patient, successful treatment of his insomnia facilitated CPAP concordance, which likely contributed to a reduction in seizure frequency and, by inference, to a lower risk of SUDEP. Case 5 had co-occurring insomnia and CRSD which is characteristic of Smith–Magenis syndrome.20 Restoring the patient’s nocturnal sleep pattern to 5–6 hours in one block was associated with a reduction in behavioural disturbances which are also a feature of this genetic neurodevelopmental disorder.

Melatonin is a key regulator of the sleep–wake cycle.21 Amongst recommended pharmacological treatments for chronic insomnia, melatonin has received the most attention likely because of its favourable safety profile, which is particularly important in the presence of multimorbidity and polypharmacy.1,2 A meta-analysis of placebo-controlled randomized trials (9 trials, 183 patients) of melatonin in individuals with intellectual disabilities and sleep problems found that melatonin treatment significantly decreased sleep latency (p<0.001) and number of wakes per night (p<0.05) and increased total sleep time (p<0.001).22 None of the four patients in our series who previously trialled melatonin had achieved a successful outcome. In contrast, treatment with daridorexant was associated with substantial and sustained improvements in sleep in all patients, including the four who had failed melatonin. Daridorexant offers a novel approach to treating chronic insomnia by specifically inhibiting the action of wake-promoting neuropeptides.10

Chronic insomnia typically requires a long-term solution. Our case series described three patients who had been treated continuously with daridorexant for 6 (Case 4), 9 (Case 5) and 14 (Case 3) months without waning of effect or any apparent safety issues. Albeit limited, such evidence for a prolonged treatment effect and good tolerability in these cases aligns with previous data regarding long-term use of daridorexant in the general population12 and may provide some reassurance when considering its use in adults with intellectual disabilities. As expected in a population with multiple comorbidities, daridorexant was used concurrently with other psychoactive medications (e.g. lurasidone, aripiprazole, sodium valproate/lamotrigine, trazodone and olanzapine). The absence of interactions between daridorexant and concomitant medications is particularly relevant in view of the usual approach of achieving adequate control of comorbid mental health conditions before considering an option to manage chronic insomnia.16 However, because daridorexant is metabolized primarily by CYP3A4, its dose should be reduced when coprescribed with moderate CYP3A4 inhibitors and its concomitant use with strong CYP3A4 inhibitors or with moderate or strong CYP3A4 inducers is not recommended.9

Although no other literature exists specific to daridorexant use in adults with intellectual disabilities, Italian investigators reported their experience of treating 66 patients with insomnia disorder and comorbid mental health disturbances (mainly unipolar/bipolar depression, anxiety disorders and substance use disorders) with daridorexant 50 mg in clinical practice. After 3 months’ treatment, significant improvements from baseline were measured across a range of instruments: Insomnia Severity Index, Beck Depression Inventory-II, Young Mania Rating Scale, Self-Reported Anxiety Scale, Suicidal Ideation Scale, Dysfunctional Beliefs About Sleep, and Pre-Sleep Arousal Scale. Similar to our experience, the authors inferred that, by targeting insomnia, it may be possible to improve not only insomnia but also comorbid symptoms.23

The combination of disturbed nocturnal sleep and increased challenging behaviours in adults with intellectual disability can result in higher social care and healthcare utilisation. Modelling in general insomnia populations suggests that daridorexant is likely to be cost-effective;24 whether similar benefits extend to adults with intellectual disabilities is unknown.

Available clinical evidence indicates that daridorexant is effective for insomnia disorder even in the presence of OSA. A post hoc analysis of the daridorexant phase III study evaluated its efficacy and safety based on insomnia variables and daytime functioning in the patient subgroup with untreated mild OSA (apnoea–hypopnoea index 5 to <15 events/hour). Compared with placebo, daridorexant 50 mg improved wake after sleep onset, latency to persistent sleep, self-reported total sleep time, and the Insomnia Daytime Symptoms and Impacts Questionnaire total score over time, and was well tolerated.25 A systematic review and meta-analysis of randomized controlled trials of dual orexin receptor antagonists (daridorexant, lemborexant and suvorexant) concluded that these agents improve sleep and do not impair nocturnal respiratory function in patients with OSA.26 In the present series, the observed clinical improvement in sleep and caregiver-reported CPAP use in the patient with comorbid OSA (Case 4) is consistent with, though cannot prove, these trial-based findings; CPAP monitoring in this case relied on routine clinical review and caregiver-reported use rather than formal quantitative adherence downloads.

This case series describes experience with daridorexant in a limited number of adult patients with intellectual disabilities treated at a single centre and, as such, the observations are best interpreted as hypothesis-generating. As a reflection of the challenges inherent in treating non-verbal patients with multiple comorbidities, the findings are entirely subjective and largely limited to caregiver observations. There is risk of recall and expectation bias in retrospective narrative reports, though this may have been mitigated to some extent by close patient follow-up. Given the communicative limitations, structured scales, such as the Epworth Sleepiness Scale, were not feasible and such data were not routinely collected; future prospective work should explore pragmatic caregiver-completed instruments where feasible. Notwithstanding these limitations, as a first-ever report of daridorexant use in adults with intellectual disabilities, we consider the article to be of value to healthcare professionals and the broader community involved in the care of these patients. Interesting aspects of the series include the complexity of each case, the extent to which improving nocturnal sleep can moderate the manifestations of comorbid conditions, and the marked clinical benefit observed in all five patients treated with daridorexant over the reported timeframe.

Conclusion

In the absence of clinical evidence specific to the management of chronic insomnia in adults with intellectual disabilities, recommendations are extrapolated from those for the general population. Here, we have shown that daridorexant may offer clinically meaningful benefit in this patient group by normalising nocturnal sleep with an associated reduction in excessive daytime sleepiness. Improving sleep quality and quantity was also associated with reductions in challenging behaviours and psychotic episodes, enhanced CPAP concordance in the presence of comorbid OSA, and alleviation of parent and carer burden. Given that CBTi for insomnia disorder may not be feasible in certain individuals with intellectual disabilities, we consider that daridorexant offers clinicians a valuable treatment option. In this series of patients, daridorexant was well tolerated and provided sustained improvement in insomnia symptoms, including during concomitant use with other psychoactive medications, with no apparent safety issues over the observed treatment periods. Aligning with NICE recommendations, we emphasize the need for health practitioners to reinforce behavioural sleep medicine advice alongside use of medicines in clinical practice.