Suvorexant for the treatment of insomnia in patients with Alzheimer’s disease

To the Editor

Orexin, a neuropeptide produced by the lateral hypothalamic neurons, contributes to the regulation of the sleep–wake cycle by increasing arousal levels and maintaining wakefulness. Suvorexant is the newest orexin-receptor antagonist (Sakurai et al., 1998). It has been reported that patients with moderate to severe Alzheimer’s disease (AD) present with higher mean orexin levels and more impaired nocturnal sleep (Liguori et al., 2014). We conducted a 4-week, prospective, structured clinical trial to determine the efficacy, side effects and tolerability of suvorexant for the treatment of insomnia in patients with AD.

In total, six consecutive patients with AD (five females and one male, mean age, 87.5 ± 7.09 years) presenting with insomnia, monologue and screaming were enrolled. Patients were not allowed to have changed drugs within 2 weeks before inclusion in the study. Dementia due to AD was diagnosed using the criteria of the International Classification of Diseases, Tenth Revision (Code F00.1). Insomnia was defined as the difficulty in sleeping more than 4 hours continuously in one night and on more than three nights a week. After explaining the study to patients and caregivers, written informed consent was obtained.

Treatment was initiated with a suvorexant dose starting at 15 mg, and the dose was increased to 20 mg as needed. The patients were evaluated at baseline and in weeks 1, 2, 3 and 4. Cognitive functions, activities of daily living scores, and behavioral and psychological symptoms of dementia were determined by the Mini Mental State Examination (MMSE), Physical Self-Maintenance Scale (PSMS) (Lawton and Brody, 1969) and Neuropsychiatric Inventory (NPI). With regard to side effects, we specifically monitored patients for somnolence, headache and weakness during the follow-up period.

All patients completed the clinical trial, and by completion, all of them were able to sleep continuously for 6 hours per night. The suvorexant dose at the end-point was 15 mg in one patient and 20 mg in five patients. The mean baseline scores (with the overall changes by the study end-point) for the MMSE and PSMS were 5.7 ± 5.89 (−0.8 ± 1.17) and 10.8 ± 5.53 (−0.33 ± 0.82), respectively. The mean changes in NPI scores ranged from −1.17 to 1.0 points. The improvements without insomnia were not observed. No side effects were observed during the follow-up period.

The results of this study indicate that suvorexant has adequate efficacy for the treatment of insomnia in patients with AD.