Oral Hypnotics in Common Use

Benzodiazepine receptor agonists: Benzodiazepines

TriazolamTriazolam

1.5−5.5

May cause anterograde amnesia; high likelihood of tolerance and rebound after repeated use

TemazepamTemazepam

9.5–12.4

Longest latency for sleep induction

EstazolamEstazolam

10–24

Effective for sleep induction and maintenance

QuazepamQuazepam

39–100

High lipophilicity, which may mitigate residual sedation in first 7–10 days of continuous use

FlurazepamFlurazepam

47–100

High risk of next-day residual sedation; not recommended for older adults

Benzodiazepine receptor agonists: Nonbenzodiazepines

ZaleplonZaleplon

1

Ultrashort-acting; can be given for sleep-onset insomnia or after nocturnal awakening (if patients can spend at least 4 hours in bed after taking the drug)

When given at normal bedtime, least likely to have residual effects

Zolpidem, tabletsZolpidem, tablets

2.5

Effective for sleep-onset insomnia only

Zolpidem oral sprayZolpidem oral spray

2.7

Used for sleep-onset insomnia; has a rapid onset of action

Zolpidem, extended-releaseZolpidem, extended-release

2.8

Effective for sleep-onset insomnia and sleep maintenance insomnia; no tolerance with up to 6 months of use 3 to 7 nights/week

Zolpidem, sublingualZolpidem, sublingual

2.9

More rapid onset of action than zolpidem tabletsMore rapid onset of action than zolpidem tablets

Higher doses used for sleep-onset insomnia

Lower doses used for early awakening (should not be taken unless patients can spend at least 4 hours in bed after taking the drug)

EszopicloneEszopiclone

6

Effective for sleep-onset insomnia and sleep maintenance insomnia; no tolerance with up to 6 months nightly use

Melatonin receptor agonistsMelatonin receptor agonists

TasimelteonTasimelteon

0.9–1.7

Can increase nighttime sleep duration and decrease daytime sleep duration in totally blind patients who have non–24-hour sleep-wake syndrome

Can cause headaches and abnormal dreams or nightmares (most common adverse effects); no apparent abuse liability

RamelteonRamelteon

1–5

Useful only for sleep-onset insomnia; one of a few hypnotics that are not associated with abuse liability

Can be safely given to patients with mild to moderate obstructive sleep apnea or chronic obstructive pulmonary disease (COPD)

No difficulties with long-term use

Orexin receptor antagonists

Daridorexant Daridorexant

About 8

Used for sleep-onset and/or sleep maintenance insomnia

Can cause headaches, somnolence, fatigue (most common), and suicidal ideation, worsening of depression, sleep paralysis, and complex sleep-related behaviors (eg, sleepwalking, sleep driving)

LemborexantLemborexant

17 (with 5 mg)

19 (with 10 mg)

Used for sleep-onset and/or sleep maintenance insomnia

Can cause somnolence (most common) and suicidal ideation, worsening of depression, sleep paralysis, and complex sleep-related behaviors (eg, sleepwalking, sleep driving)

Contraindicated in patients with narcolepsy

SuvorexantSuvorexant

12

Useful for sleep-onset and maintenance insomnia

Use lowest effective dose; may be increased to a maximum of 20 mg once a day if the 10-mg dose is well-tolerated but not effective

Tricyclic antidepressant

Doxepin, ultra low doseDoxepin, ultra low dose

15.3

Indicated for sleep maintenance insomnia; no abuse liability