Sleep Strategies

The quest for a good night’s sleep: An update on pharmacologic therapy for insomnia


Current medications used to treat insomnia are listed in Tables 2 and 3, some of which carry an FDA approval to be used as a hypnotic, while others are used in an off-label manner.

FDA-approved medications

Cautions abound with use of many of these medications. Common concerns include safety, particularly for elderly patients and long-term use, and the potential for developing tolerance and dependence.

Off-label medications

Most medications that have been used for insomnia have been available for decades, but, in recent years, a new class of hypnotics has emerged. Dual orexin receptor antagonists (DORAs) are the newest class of FDA-approved medications (Table 4).

Dual orexin receptor antagonists

Orexin is a neuropeptide found primarily in the lateral hypothalamus and binds to the orexin 1 and orexin 2 receptors leading to a number of downstream effects, including stimulating wakefulness. Loss of orexin-generating neurons has been implicated as the cause of type 1 narcolepsy, and antagonism of their effects can facilitate sleep by suppressing wakefulness. The first medication in the DORA class to be FDA-approved was suvorexant in 2014, followed by lemborexant’s FDA approval in 2019. These are both indicated for treating sleep onset and sleep maintenance insomnia and have been shown to improve both subjective and objective measures of sleep. The most common side effects reported for both suvorexant and lemborexant are headache and somnolence, with morning-after sleepiness being a frequent complaint.

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