Ramelteon (Rozerem): A Novel Treatment Option for Patients with Insomnia

INTRODUCTION Over the past decade, drug companies have focused much of their attention on addressing the problem of insomnia. This effort should come as no surprise— insomnia is being reported at an alarmingly high rate. In 2005, the National Sleep Foundation, part of the National Institutes of Health, estimated that more than half (54%) of all Americans were reporting symptoms of insomnia a few nights a week, and one third (33%) were reporting symptoms nearly every night. Epidemiologists have suggested that 10% to 20% of people in the U.S. and in Western Europe experience chronic insom nia. These statistics clearly dem onstrate a need for sleep medications and an opportunity for the pharmaceutical industry to develop new and improved sleep aids with hopes of promising revenues while improving outcomes in patient health care and quality of life. Most medications available for insomnia focus on modulation of the GABA ergic system. Because of the properties of most currently prescribed medications, which act primarily by enhancing the neurotransmitter gamma-amino butyric acid (GABA) at its receptors through binding to benzodiazepine (BZD) receptors as allosteric modulators, they are classified as controlled substances and carr y some risk for dependence or abuse. These sleeppromoting agents include the older benzo diazepines: flurazepam (Dalmane, ICN), temazepam (Restoril, Malinckrodt), triazolam (Halcion, Pfizer), estazolam (ProSom, Abbott), and quazepam (Doral, Wallace) as well as newer agents, the non-benzodiazepines. The nonbenzo diazepines selectively act on the BZD1 receptors and include zolpidem tartrate (Ambien, Sanofi-Aventis), zaleplon (Son ata, King/Wyeth), and eszopiclone (Lunesta, Sepracor). The newer medications are fairly well tolerated, and their risk for abuse or dependenc e is lower than that of the older BZDs. Older sedative medications, like the BZDs, are still very effective but carry a higher risk for abuse and dependence when used over the long term. Barbiturates commonly have a high potential for abuse, dependence, and toxicity; generally, they are no longer recommended for sleep. In addition to the problems of abuse and dependence, drugs that act by modulating GABA are especially complicated in elderly people. According to the updated Beers criteria for potentially in appro priate medications used in older adults, benzo diazepines are of great concern. They have been reported to cause prolonged sedation; an increased risk of falls, possibly leading to fractures; cognitive impairmen t; dizziness; and de pressio n. These drugs are not usually recommended for patients 65 years of age or older unless they are considered ab solutely necessary. Similarly, barbiturates are contra indicated for insomnia in the elderly and carry an increased risk of side effects and toxicity. Even non-benzodiazepines, although much safer than barbiturates and benzodiazepines, can cause con fusion and increased falls in older adults. These concerns of drug abuse, dependence, and problematic side effects highlight the need and opportunities for the development of innovative therapies for insomnia. One agent, approved by the Food and Drug Administration (FDA) in 2005, is ramelteon (Rozerem, Takeda Pharmaceuticals). Ramelteon is the first FDA-approved medication that acts on melatonin receptors. As a result of this mechanism of action, the dependence and abuse potential are eliminated; therefore, ramelteon does not need to be restricted as a controlled substance. In addition, dose reductions are not required in the elderly. This drug may even be beneficial in blind or neurologically compromised patients for whom other insomnia treatments are in effective or contraindicated.