Making sleep easier: pharmacological interventions for insomnia

ABSTRACT

Introduction: The disorder insomnia represents a relevant and frequent condition in clinical care. Cognitive behavioral therapy of insomnia (CBT-I) is regarded as first line treatment. Pharmacotherapy can be considered if CBT-I is not available or effective. Therefore, pharmacological approaches for disturbed sleep are still among the most widely prescribed pharmacological treatments in clinical care.

Areas covered: In this review, the authors highlight basic physiological pathways of sleep regulation to understand fundamental pharmacological principles of sleep medicine. Available guidelines and reviews are summarized and recommendations formulated regarding the use of benzodiazepines and hypnotic benzodiazepine receptor agonists, melatonin and melatonin receptor agonists, sedating antidepressants, antipsychotics and antihistamines, and orexin receptor antagonists in insomnia disorder. Variations in the treatment of insomnia disorder in subpopulations with increased prevalence of sleep disorders – childhood, pregnancy and old age – are specified.

Expert opinion: The well-established off-label use of hypnotic drugs should evocate a debate about a better alignment of clinical practice and scientific evidence and guidelines. Better understanding of sleep regulation could help in the development of completely new substance classes. Focusing subjective sleep disturbances, such as superficial sleep perception might help identify novel pathways.

KEYWORDS:

• Hypnotics
• melatonin
• benzodiazepines
• medication
• antidepressants
• elderly
• pregnancy
• children

Article highlights

• Cognitive behavioral therapy of insomnia should be considered as first line treatment of insomnia disorder (ID) across all ages.

• Clear pharmacological recommendations for ID only exist for the short-term treatment of adults with some benzodiazepines (BZ), hypnotic benzodiazepine receptor agonists (HBRA) and sedating antidepressants, namely doxepin and trazodone, if CBT-I is not available or not effective.

• For ID in children and adolescents, BZ, HBRA and antihistamines are advised against, melatonin might be useful in children with sleep onset problems and sedating antidepressants and antipsychotics should be restricted to patients suffering from comorbid psychiatric diseases.

• During pregnancy, BZ and HBRA could be used in very severe cases of ID and zolpidem should be considered first, if treatment is needed. Limited data exists on trazodone or mirtazapine during pregnancy while antihistamines, antipsychotics, and melatonin should be avoided.

• In the elderly, BZ and HBRA are advised against without consideration of duration in patients aged 65 years or older. Melatonin and ramelteon might be more efficacious in older patients and suvorexant displays promising results. Antihistamines, antipsychotics and antidepressant medication should be used carefully due to anticholinergic side effects. Doxepin in doses from 3 to 6 mg per day might be a. feasible treatment option.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.