Suvorexant in Patients With Insomnia: Results From Two 3-Month Randomized Controlled Clinical Trials

Suvorexant in Patients with Insomnia: Pooled Analyses of Three-Month Data from Phase-3 Randomized Controlled Clinical Trials

“…These prespecified analyses of pooled data from phase-3 trials 8 showed that 20/15 mg doses of suvorexant improved selfreport and PSG measures of sleep onset and sleep maintenance at the initiation of treatment and over 3 months of nightly use. Generally, effects were greater on objective than subjective measures.…”

“…1,2 Sixteen years later, in 2014, suvorexant became the first agent specifically targeting the orexin system (via orexin receptor antagonism) to be approved as a therapeutic agent, for the treatment of insomnia. [3][4][5][6][7][8] This relatively rapid progress reflects advances in understanding orexin biology. The orexin signaling system comprises of a restricted number (50,000-80,000) of orexin neurons which originate from the lateral hypothalamus and project widely throughout the central nervous system.…”

“…16 This approach is distinct from current insomnia drugs, most of which promote sleep by enhancing sleep signaling via gamma-aminobutyric acid (GABA) inhibitory effects. 17 The suvorexant phase-3 development program in insomnia patients was comprised of two 3-month pivotal trials, each of which evaluated two age-adjusted (non-elderly/elderly) dose regimes of 40/30 mg and 20/15 mg, 8 and a 1-year trial of 40/30 mg. 7 The primary objective of the trials was to establish the efficacy, safety, and tolerability of the 40/30 mg dose. By design, fewer…”

Mechanism of action of suvorexant

“…1-3 Reversible pharmacologic blockade of orexin receptors is now proven to be a novel hypnotic mechanism ( Figure 4). [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Other potential clinical applications, based on preclinical studies, could eventually include use for weight loss or drug abuse. 1,4,6,7,12 Dual orexin receptor antagonists (DORAs) that block both orexin 1 and 2 receptors, and single orexin receptor antagonists (SORA-1s and SORA-2s) that selectively block either orexin 1 receptors or orexin 2 receptors, have also been developed ( Figure 4) and are being extensively tested at this time.…”

“…[1][2][3] The novel DORA suvorexant is now an approved hypnotic that improves both the initiation and maintenance of sleep in human subjects, without the side effects expected of a benzodiazepine or Z drug hypnotic, namely, dependence, withdrawal, rebound, unsteady gait, falls, confusion, amnesia, or respiratory depression. [1][2][3][12][13][14][15][16] Figure 2. Hypocretin/orexin neurotransmission is mediated by 2 types of postsynaptic G-protein-coupled receptors, orexin 1 (Ox1R) and orexin 2 (Ox2R).…”