Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial

Hypnotics cause insomnia: evidence from clinical trials

“…This study demonstrated a lasting "return of insomnia" [their words, that "Abrupt discontinuation of suvorexant under double-blind conditions was not associated with ... significant withdrawal or rebound insomnia." 4 In my opinion, these three placebo-controlled trials observed withdrawal insomnia throughout one, four, and eight weeks after hypnotic discontinuation, leaving patients who had received the hypnotic worse off than those randomized to placebo. The hypnotics CAUSED insomnia, principally by prolonging sleep latency, and the harm lasted as long as observation persisted.…”

“…In a one-year trial of suvorexant 30-40 mg. using subjective outcomes, 4 the investigators proposed a drug-rebound criterion requiring exacerbation worse than the insomnia at baseline.…”

Preventive Effects of Suvorexant on Delirium

“…Suvorexant, a potent and selective orexin receptor antagonist, recently approved by the US Food and Drug Administration for the treatment of insomnia, is noted for subjective measures of sleep onset and maintenance, 21 without major changes in the patient's neurophysiology as assessed by electroencephalographic power spectral density. 22 In practice, we experienced that a lot of acutely admitted patients with risk factors of delirium such as advanced age, dementia, and history of delirium did not develop delirium after suvorexant was given for insomnia, without obvious side effects.…”

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).…”