Physician's Weekly Article - New Parameters for Treating Narcolepsy & Other Hypersomnias

       Significant advances in the treatment of narcolepsy and other hypersomnias of central origin have occurred since 2000. As such, practice parameters have been updated to further aid physicians in diagnosing and treating these burdensome conditions.

      Narcolepsy occurs in just one of every 2,000 Americans, but the prevalence of the disorder may be much higher. “Only 25% to 30% of people who have narcolepsy, cataplexy, or hypersomnia have been correctly diagnosed,” explains Todd J. Swick, MD, FAAN, FAASM. “Many patients are undiagnosed or will be misdiagnosed with depression, attention deficit disorder, or substance abuse problems.” The average narcoleptic patient sees six physicians during the course of their illness. After symptom onset, many go 10 to 12 years before receiving an appropriate diagnosis. This treatment gap must be addressed because narcolepsy and other sleep disorders such as hypersomnia can have a significant impact on patients’ quality of life. These disorders affect their ability to function in familial, social, and occupational settings.

      Narcolepsy is characterized largely by irresistible daytime sleepiness, but cataplexy (the sudden loss of muscle tone), vivid hallucinations during sleep onset or upon awakening, and brief episodes of total paralysis at the beginning or end of sleep also accompany this condition for many patients. Hypersomnia is different in that it is characterized by recurrent episodes of excessive daytime sleepiness or prolonged nighttime sleep. Unlike narcolepsy, patients with hypersomnia are compelled to nap repeatedly during the day, often at inappropriate times (eg, at work, during meals, or in conversation). These naps usually provide no relief from symptoms, which include difficulty waking, disorientation, anxiety, increased irritation, decreased energy, restlessness, slow thinking, slow speech, and memory difficulty.

      Practice Parameters Revisited

      The American Academy of Sleep Medicine (AASM) conducted an initial review of medical literature and released guidelines on stimulant therapies for narcolepsy in 1994. A second review was conducted in 2000 and included therapies other than stimulants for the condition. Since 2000, however, significant research has emerged addressing the safety and efficacy of the available therapies to treat narcolepsy. The AASM believed that these new drugs were so important to the clinical treatment paradigm that practice guidelines were revised yet again in 2007 to reflect the emergence of new pharmacologic treatments. The updated practice parameters were published in the December 2007 issue of Sleep.

      “The new agents for narcolepsy and hypersomnias are so effective that the AASM believed it was critical to include these drugs as standards of treatment,” says Dr. Swick, who co-authored the most recent AASM parameters. “This represents a breakthrough in therapies because many of the drugs being used to treat the condition had not been approved by the FDA in 2000.” Furthermore, the AASM published a revised coding manual in 2005, which included 12 disorders under the category of hypersomnia of central origin. For example, the new manual addresses disorders in which daytime sleepiness is the primary complaint, but the cause of this symptom is not due to disturbed nocturnal sleep or misaligned circadian rhythms. The newly released parameters update previous recommendations for using therapies for narcolepsy and address the treatment of other hypersomnias of central origin, including idiopathic hypersomnia, recurrent hypersomnia, and hypersomnia due to medical conditions.

      Weighing the Evidence

      For the new practice parameter, an AASM committee of board-certified sleep specialists, invited experts, and key opinion leaders in narcolepsy and hypersomnias evaluated what has changed in clinical practice and the new FDA-approved treatments over the past several years. Dr. Swick notes that each citation is graded by strength of evidence to determine if it should become a standard of treatment, a guideline, or a recommendation (Table 1). “Many treatment recommendations only applied to narcolepsy in previous publications,” he adds. “However, these therapies have also been used to treat hypersomnias of central origin. A key goal of the updated practice parameters is to address where each of these therapies fits into treatment protocols. The standards of treatment are accepted patient-care strategies (in general) that reflect a high degree of clinical certainty. Guideline items are patient-care strategies that reflect a moderate degree of clinical certainty, and other treatment options are provided to enhance patient-care strategies, which reflect uncertain clinical use.”

      A Bright Future

      Over the past decade, considerable progress has been made in understanding the pathogenesis of narcolepsy and in identifying genes that are strongly associated with the disorder. “Identifying the cause of narcolepsy was a critical first step in finding potential cures,” Dr. Swick says. “It has helped lead clinicians, researchers, and drug developers to dramatically improve our treatment armamentarium. The hope is that the new AASM parameters will increase physicians’ ability to adhere to recommended diagnostic and treatment options and to ultimately improve patient outcomes. Furthermore, there’s still hope that we can cure this disease in the long term with continued research efforts.”

      Todd J. Swick, MD, FAAN, FAASM, has indicated to Physician’s Weekly that he has worked as a consultant for Jazz Pharmaceuticals and as a paid speaker for GlaxoSmithKline, Jazz Pharmaceuticals, Sepracor, Cephalon, and Boehringer Ingelheim. He has also received grants/research aid from Sanofi-Aventis, Takeda North America, Merck, Jazz Pharmaceuticals, Pfizer, Somaxon, Astellas Pharmaceuticals, and Cephalon.