Insomnia Pharmacotherapy

Abstract

Summary The benzodiazepine receptor agonists (BzRAs) a melatonin receptor agonist and a histamine antagonist have all been approved as hypnotics. Beyond their differing mechanisms of action, they have differences in pharmacokinetics, and among the BzRAs differences in receptor subtype affinity and formulations, which provides the physician with broad options for tailoring therapy to each patient's specific needs. Consistent with their specific pharmacokinetics and formulations, these Food and Drug Administration-approved hypnotics have been shown to improve sleep with no evidence of tolerance development in long-term use. In addition, emerging data indicate these drugs also improve aspects of daytime function. Their side effects are either associated with the direct sedating effects of the drugs, doses greater than clinical doses, or a combination with alcohol or other sedating drugs. Anxiolytic BzRAs, sedating antidepressants and antipsychotics have been used off-label as hypnotics. However, in the absence of information regarding their dose range for efficacy and safety, their use as hypnotics is ill-advised.

Sleep Disturbances: Implications for Cannabis Use, Cannabis Use Cessation, and Cannabis Use Treatment

“…A breadth of research has demonstrated the efficacy of both pharmacological (e.g., benzodiazepine hypnotics) and behavioral (cognitive behavioral therapy for insomnia, CBT-I) interventions for the treatment of insomnia and sleep disturbances [59][60][61]. Comparisons between pharmacotherapy and behavioral interventions have demonstrated comparable treatment effects, with pharmacotherapy offering a more immediate impact on sleep and behavioral interventions linked to greater long-term and sustained treatment gains [62][63][64].…”

“…Although treatment effectiveness exists for both forms of intervention, it is important to note that no study has examined comparative efficacy or effectiveness of these interventions among individuals with a history of substance use disorders. This limitation of existing work is likely due to the fact that pharmacotherapy for insomnia is typically not recommended for individuals with a history of substance use disorders owing to the risk of the development of dependence [61]. For this reason, additional research among substance use populations is needed.…”

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

“…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…”

Pharmacokinetics of Zolpidem from Sublingual Zolpidem Tartrate Tablets In Healthy Elderly Versus Non-Elderly Subjects

“…Insomnia and several other sleep disorders occur with disproportionate prevalence among the elderly, and as such hypnotic medications are commonly used by elderly individuals [1][2][3][4][5][6]. Extensive research data on hypnotic drug disposition and effects in the elderly population indicates that older persons may have reduced metabolic clearance of hypnotic medications (leading to higher plasma concentrations), increased intrinsic sensitivity to hypnotic drugs, or both [7][8][9].…”