Drugs for insomnia.
BACKGROUND
Sleep is a vital neurochemical process involving sleep-promoting and arousal centers in the brain. Insomnia is a pervasive disorder characterized by difficulties in initiating or maintaining or non-refreshing (poor quality) sleep and clinically significant daytime distress. Insomnia is more prevalent in women and old age and puts sufferers at significant physical and mental health risks. This review summarizes published data on the current and emerging insomnia drug classes, rationale for development and associated risks/benefits. (Summary of Product Characteristics and Medline search on "hypnotic" or specific drug names and "Insomnia").


METHODS
GABA(A) receptor modulators facilitate sleep onset and some improve maintenance but increase risk of dependence, memory, cognitive and psychomotor impairments, falls, accidents and mortality. Melatonin receptor agonists improve quality of sleep and/or sleep onset but response may develop over several days. They have more benign safety profiles and are indicated for milder insomnia, longer usage and (prolonged release melatonin) older patients. Histamine H-1 receptor antagonists improve sleep maintenance but their effects on cognition, memory and falls remain to be demonstrated. Late-stage pipeline orexin OX1/OX2 and serotonin 5HT2A receptor antagonists may hold the potential to address several unmet needs in insomnia pharmacotherapy but safety issues cast some doubts over their future.


CONCLUSIONS
Current and new insomnia drugs in the pipeline target different sleep regulating mechanisms and symptoms and have different tolerability profiles. Drug selection would ideally be based on improvement in the quality of patients' sleep, overall quality of life and functional status weighed against risk to the individual and public health.
Tel Aviv University, Department of Neurobiology, The George S. Wise Faculty of Life Sciences and Neurim Pharmaceuticals, Tel Aviv 69978, Israel. navazis@post.tau.ac.il
Nava
N
Zisapel
D002986:Clinical Trials as Topic; D055808:Drug Discovery; D018757:GABA Modulators / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D040541:Marketing; D009479:Neuropeptides / Q000037:antagonists & inhibitors; D000068797:Orexins; D011963:Receptors, GABA-A / Q000378:metabolism; D044094:Receptors, Melatonin / Q000819:agonists; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D016896:Treatment Outcome
D018757:GABA Modulators; D006634:Histamine H1 Antagonists; D006993:Hypnotics and Sedatives; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D011963:Receptors, GABA-A; D044094:Receptors, Melatonin; D058830:Serotonin 5-HT2 Receptor Antagonists