The role of modified-release formulations in hypnotic therapy for insomnia

In addition to the psychological and medical health risks associated with lack of adequate sleep, effects of insomnia include impaired daytime functioning and decreased quality of life. Many patients experience delayed sleep onset, frequent awakenings, early waking, or nonrestorative sleep. Longitudinal data on insomnia indicate that the prevalence of persistent/chronic insomnia is high and appears to be characterized by multiple symptoms related to initiating or maintaining sleep. Physiologic studies indicate that short-term sleep restriction can cause physiologic problems that lead to long-term health consequences, such as high blood pressure, impaired glucose tolerance, and systemic inflammation. Epidemiologic studies have shown that sleep deprivation is independently associated with increased risk of cardiovascular disease, diabetes, obesity, and mortality. While the available agents are effective, those with a long half life may have carryover effects while short-acting agents may not provide enough sleep continuity. Pharmacologic therapies available for patients who suffer from insomnia include immediate-release nonbenzodiazepine hypnotics, which have a positive benefit/risk profile compared to the benzodiazepines. Modified-release (MR) formulations of these agents may offer the additional benefit of improving sleep continuity throughout the night without sacrificing the rapid elimination properties that minimize next-day residual effects. MR agents in development include zolpidem MR and indiplon MR.