SEROTONIN 5-HT2A RECEPTOR ANTAGONISTS IN THE TREATMENT OF INSOMNIA: PRESENT STATUS AND FUTURE PROSPECTS

Benzodiazepine (BZD) and non-BZD hypnotics improve sleep induction and sleep maintenance. BZD induces a further reduction of slow wove sleep (SWS) and rapid eye movement (REM) sleep, whereas SWS and REM values remain decreased during non-BZD administration. There is evidence indicating that the nonselective serotonin 5-HT2A/2C receptor antagonists, ritanserin, ketanserin, seganserin and ICI-169369, the selective 5-HT2A receptor antagonist eplivanserin and the 5-HT2A receptor inverse agonist pimavanserin, increase SWS in subjects with normal sleep. In addition, it has been shown that prior administration of ritanserin prevents the nitrazepam-induced suppression of SWS in normal subjects. Of note, ritanserin also induced on increase of SWS in poor sleepers, patients with chronic primary insomnia and psychiatric patients with a generalized anxiety disorder or a mood disorder. The 5-HT2A receptor inverse agonist APD-125 gave rise to a similar effect in patients with chronic primary insomnia. Thus, presently available evidence tends to indicate that the association of a 5-HT2A receptor antagonist or a 5-HT2A receptor inverse agonist with a BZD or a non-BZD hypnotic could be a valid alternative to normalize SWS in patients with primary or comorbid insomnia.