title: Pharmacotherapy of insomnia.
abstract: BACKGROUND
  Insomnia is one of the most prevalent sleep disorders in developed countries, being surpassed only by chronic sleep deprivation. Patients with insomnia tend to have an altered quality of life, impaired daytime functioning and an increased risk of work accidents and motor vehicle crashes. Insomnia is commonly associated with chronic medical conditions, metabolic illnesses and mental disorders (such as depression and anxiety), with which there is a dual, reciprocal relationship.
  
  
  METHODS
  This paper focuses on current pharmacotherapy options for the treatment of insomnia, particularly benzodiazepine receptor agonists, which nowadays represent the mainstay of hypnotic therapy. The melatonin receptor antagonist, ramelteon, is reviewed (an alternative for some patients with only sleep-onset difficulty), as are sedating antidepressants, which are commonly used 'off-label' to treat insomnia, despite limited efficacy data and potential significant safety concerns. Orexin (OX) antagonists are also discussed, especially those that block OX2 or both OX1 and OX2 receptors, as these are the most promising new agents for the treatment of insomnia, with encouraging results in preliminary clinical trials.
  
  
  CONCLUSIONS
  Research to evaluate and formulate treatments for insomnia is often complicated by the fact that insomnia is usually of multifactorial etiology. Understanding the molecular and receptor mechanisms involved in promoting sleep in varied disorders could provide future approaches in new drug development. In the long term, more randomized controlled trials are needed to assess both short-term and long-term effects of these medications and their efficacy in comorbid diseases that affect sleep quality or quantity.
authors.affiliation: Emory School of Medicine, Atlanta VA Medical Center, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Atlanta, GA, USA.
authors.forename: Octavian C
authors.initials: OC
authors.lastname: Ioachimescu
authors.forename: Ali A
authors.initials: AA
authors.lastname: El-Solh
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000627:therapeutic use*; D004366:Nonprescription Drugs / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D012890:Sleep / Q000187:drug effects*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D006993:Hypnotics and Sedatives; D004366:Nonprescription Drugs