Sleep maintenance insomnia: strengths and weaknesses of current pharmacologic therapies.
BACKGROUND
Although insomnia is highly prevalent, sleep disturbances often go unrecognized and untreated. When insomnia is recognized, considerable emphasis has been placed on improving sleep onset; however, there is growing evidence that improving sleep maintenance is an equally important treatment goal.


METHODS
A MEDLINE literature search was performed using the search parameters "insomnia," "zolpidem," "zaleplon," "flurazepam," "estazolam," "quazepam," "triazolam," and "temazepam," as these agents are FDA-approved for the treatment of insomnia. Per reviewer comments, the search criteria was later expanded to include lorazepam. A literature search using the terms "trazodone" and "insomnia" was also performed, as this is the second-most commonly prescribed agent for treating insomnia. Sleep efficacy endpoints from randomized, placebo-controlled clinical trials in adult populations and key review articles published between 1975 and 2004 were included in this review. As only one randomized placebo-controlled trial evaluated trazodone use in primary insomnia, the trazodone search was expanded to include all clinical trials that evaluated trazodone use in insomnia. Relevant texts and other articles that evaluated side effect profiles of these agents were also included, one of which was published in January of 2005. In all publications, impact of treatment on sleep maintenance parameters (wake time after sleep onset, number of awakenings) and measures of next-day functioning were evaluated, in addition to sleep onset parameters (sleep latency, time to sleep onset/induction) and sleep duration data (total sleep time).


RESULTS
Many of the currently available agents used to treat insomnia, including the antidepressant trazodone, the non-benzodiazepine hypnotics zolpidem and zaleplon, and some of the benzodiazepines, have not consistently demonstrated effectiveness in promoting sleep maintenance. Furthermore, the benzodiazepines with established sleep maintenance efficacy are associated with next-day sedation, the risk of tolerance and dependence, or both.


CONCLUSIONS
New agents that offer relief of sleep maintenance insomnia without residual next day impairment while improving next day function are needed. Several compounds currently under development may offer clinicians a more effective and safer treatment for this common disorder.
Rosenberg
Russell P
RP
Northside Hospital Sleep Medicine Institute, Atlanta, GA, USA. rosenberg@mindspring.com
D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use; D001143:Arousal / Q000187:drug effects; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012890:Sleep / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D014196:Trazodone / Q000009:adverse effects / Q000627:therapeutic use; D014851:Wakefulness / Q000187:drug effects; D000077334:Zolpidem
D000081:Acetamides; D006993:Hypnotics and Sedatives; D011725:Pyridines; D011743:Pyrimidines; D001569:Benzodiazepines; D000077334:Zolpidem; C085665:zaleplon; D014196:Trazodone