Recent Advances and Emerging Pharmacotherapeutic Approaches for Central Hypersomnolence Disorders

Pharmacological management has been the backbone of treatment for disorders of central hypersomnolence despite challenges in drug administration due to intolerable side effects, development of tolerance, and addiction potential. Recent advances in drug therapies for central hypersomnolence disorders, namely sodium oxybate and orexin agonists, have either changed or increased the potential to significantly improve the quality of life of individuals with narcolepsy and idiopathic hypersomnia. Mechanisms of action, pharmacodynamics and pharmacokinetics of previously and commonly used medications, along with the evidence behind their use, are discussed. In addition, oveporexton, an orexin receptor 2 agonist (OX2R) will be discussed as it marks an important first step in directly counteracting the pathology behind narcolepsy with cataplexy and has completed Phase 2 trials with Phase 3 underway. Early clinical data is promising; however, its long term efficacy and safety data is insufficient to garner US Food & Drug Administration approval, though additional trials are ongoing in narcolepsy with cataplexy, and non-orexin deficient central hypersomnolence disorders as well. Regardless, new drug developments may lead expanded treatment options and may have the potential to decrease or potentially eliminate the need for polypharmacy in the treatment algorithm for narcolepsy and idiopathic hypersomnia.