PHARMACOTHERAPY | SleepTech

Pharmacotherapy in Sleep Medicine

While behavioral interventions (like CBT-I for insomnia or PAP for OSA) are first-line, pharmacotherapy remains a critical tool for acute management, specific disorders (like Narcolepsy/RBD), and refractory cases.

Classes of Hypnotics

• Benzodiazepine Receptor Agonists (BZRAs or Z-drugs): Zolpidem, Eszopiclone, Zaleplon. Enhance GABAergic inhibition. Effective for acute insomnia but carry risks of tolerance, dependence, and complex sleep behaviors (parasomnias).
• Dual Orexin Receptor Antagonists (DORAs): Suvorexant, Lemborexant, Daridorexant. Block the wake-promoting neuropeptide orexin. They alter sleep architecture less than GABAergics and have a lower theoretical risk of physical dependence.
• Melatonin Receptor Agonists: Ramelteon. Specifically targets MT1/MT2 receptors. Useful for sleep onset insomnia and circadian rhythm shifts, with negligible abuse potential.
• Off-Label Use: Sedating antidepressants (Trazodone, Mirtazapine) are widely prescribed despite limited long-term efficacy data, primarily due to their perceived safety profile regarding dependency.

Pharmacotherapy for Hypersomnolence

For disorders like Narcolepsy or Idiopathic Hypersomnia, treatments focus on increasing daytime wakefulness via dopaminergic/noradrenergic pathways (Modafinil, Solriamfetol, Amphetamines) or targeting histamine H3 receptors (Pitolisant). Sodium Oxybate (a powerful GABA-B agonist) is unique in treating both daytime sleepiness and cataplexy by consolidating nighttime sleep.

Analysis of objective outcome data, adherence rates, and long-term viability based on recent clinical trials.