Quazepam (Doral - Baker Cummins, Wallace) is a trifluoroethyl benzodiazepine made by Schering and approved in 1985 by the US Food and Drug Administration for treatment of insomnia. Like other benzodiazepines, it is a Schedule IV controlled substance.Quazepam (Doral - Baker Cummins, Wallace) is a trifluoroethyl benzodiazepine made by Schering and approved in 1985 by the US Food and Drug Administration for treatment of insomnia. Like other benzodiazepines, it is a Schedule IV controlled substance.

Estazolam (ProSom - Abbott), a triazolobenzodiazepine derivative similar in structure to alprazolam (Xanax) and triazolam (Halcion), was recently marketed in the USA for treatment of insomnia.

Three benzodiazepines and 16 other compounds are marketed in the USA for treatment of insomnia. Many authorities believe that insomnia is overdiagnosed and overtreated (MK Erman, ed, Sleep Disorders, Psychiatr Clin North Am, Volume 10, Dec 1987).

Since The Medical Letter last reviewed the choice of benzodiazepines (Volume 23, page 41, 1981), several new drugs have been marketed and some old ones are now available generically. Most of the benzodiazepines available for oral use in the USA are listed in the table on page 28.

Zolpidem (Ambien - Sanofi-Aventis), a nonbenzodiazepine benzodiazepine receptor agonist, is the most frequently prescribed hypnotic in the US. As its patent approaches expiration, its manufacturer has received FDA approval to market an extended-release formulation of the drug, Ambien CR. The pharmacological rationale for doing so is that short-acting hypnotics like zolpidem are more effective at inducing sleep than they are at maintaining it.

The FDA has approved daridorexant (Quviviq – Idorsia), an orexin receptor antagonist, for treatment of sleep-onset and/or sleep-maintenance insomnia in adults. Daridorexant is the third orexin receptor antagonist to be approved for this indication; suvorexant (Belsomra) and lemborexant (Dayvigo) were approved earlier.

Zaleplon, a pyrazolopyrimidine hypnotic, was recently approved by the FDA for short-term treatment of insomia. Zaleplon, like zolpidem, is a non-benzodiazepine that binds to benzodiazepine receptors.

The FDA now requires boxed warnings in the package inserts of benzodiazepines describing the potential for these drugs to be abused and misused and to cause addiction and physical dependence. Benzodiazepine labels have contained a boxed warning about a risk of serious drug interactions with opioids since 2016.

The physiologic changes that occur with aging can affect the pharmacokinetics and pharmacodynamics of many prescription and over-the-counter drugs, increasing the likelihood of adverse effects.

The FDA has approved lemborexant (Dayvigo – Eisai), an orexin receptor antagonist, for treatment of sleep-onset and/or sleep-maintenance insomnia in adults. It is the second orexin receptor antagonist to be approved for this indication; suvorexant (Belsomra) was the first.