Clinical practice guidelines for switching or deprescribing hypnotic medications for chronic insomnia: Results of European neuropsychopharmacology and sleep expert's consensus group

Abstract

Introduction: Current guidelines recommend cognitive behavioural therapy for insomnia (CBT-I) as the first-line treatment for chronic insomnia. Pharmacological recommendations by European guidelines for the treatment of insomnia disorder include positive GABAergic modulators such as short and medium acting benzodiazepines and "Z-drugs" (eszopiclone, zaleplon, zolpidem, zopiclone), dual orexin receptor antagonists (DORAs; daridorexant), melatonin receptor agonists (melatonin 2 mg prolonged release - PR). Given the chronic nature of insomnia, the presence of non-responders to some treatments it is often necessary switching between various therapeutic approaches and medications. However, clear guidance regarding safe and effective protocols for switching these medications currently lacks in Europe.

Method: To address this gap, we used the RAND/UCLA Appropriateness to evaluate the appropriateness of procedures for switching medications prescribed for insomnia disorder. Following a systematic review of the literature conducted in accordance with the PRISMA guidelines, we then formulated some recommendations.

Results: Twenty-one papers were selected.

Conclusions: Discontinuation of Hypnotic Benzodiazepines and Z-drugs should be gradual, with dose reductions of 10-25 % each week. Multi-component CBT-I, daridorexant, eszopiclone, and melatonin 2 mg PR were shown to facilitate the gradual discontinuation of hypnotic benzodiazepines/Z-drugs within a cross-tapered program, which can be delayed when necessary. Finally, daridorexant and melatonin 2 mg PR do not require special switching or deprescribing protocols. Several sedative-hypnotic dosage reduction algorithms are proposed in this work for clinical use in real world settings.

Keywords: CBT-I; Daridorexant; Eszopiclone; Hypnotics; Insomnia; Melatonin 2 mg.