The Past, Present, and Future of Drug Development and Treatment in Sleep Disorders

Abstract

Sleep disorders are a group of medical conditions whose treatment has dramatically changed throughout history and recent years. In the past, drug treatment of these conditions was empirical and largely based on natural products such as herbal preparations to induce sleep whose real efficacy and safety, however, was mostly unknown or unproven. The first modern and scientifically based drugs such as chloral hydrate, bromide, and barbiturates to treat sleep disorders were developed around late nineteenth and early twentieth century. Subsequently, as more progresses were made in the understanding of this group of diseases, more specific, safer, and better drugs such as benzodiazepines were developed. However, the most important advancements in the area of drug treatment of sleep disorders were made in the recent years during which several and innovative drugs and drug products were developed. These drugs such as zolpidem, zolpidem sublingual formulations, doxepin, eszopiclone, ramelteon, melatonin slow release formulations, modafinil, and sodium oxybate have significantly improved the treatment of sleep disturbances. Nevertheless, there is still room for additional improvements in this area to address yet unmet medical needs and to further improve existing therapies. As scientific advancements in this area continue to be made, it is likely that in the future we will witness the development of new and better drugs and drug products to treat sleep disturbances. New molecules that are currently in the late phase of clinical development such as Lorediplon or orexin antagonists ¹ are likely to reach the market while other innovative molecules and perhaps biologic products may also be developed along with innovative formulations and drug products made of combination of different active ingredients. The goal, strategy, and the way these new therapeutic products will be developed will probably also change in the future. Re-profiling and extension of indications of existing drugs will perhaps become more common and more drugs will be developed for treatment of insomnia and especially for the other conditions that make up the group of sleep disorders. At the same time, new treatments developed for subset of patients suffering from a given sleep disturbance are also likely to become more common and finally, the design and parameters to be evaluated in regulatory clinical studies of future sleep disorder drugs will probably also change to reflect the scientific advances that will be made in this area.

After this book went to press, on Aug 13^th, 2014, the US Food and Drug Administration approved Suvorexant tablets (Belsomra) to treat difficulty in falling and staying asleep (insomnia). Suvorexant is the first approved drug of the orexin antagonists class.