Melatonin for Acute Insomnia in Adult Inpatients
Melatonin is not recommended as first-line pharmacotherapy for acute insomnia in adult inpatients, even those with low fall risk, because guideline societies explicitly state that melatonin lacks sufficient efficacy for primary insomnia and produces only minimal improvements in sleep latency (~9 minutes) with little effect on sleep maintenance. 1, 2
Guideline Position on Melatonin
The American Academy of Sleep Medicine recommends against using melatonin for chronic insomnia, stating that benefits are approximately equal to harms, with weak evidence supporting its use for primary sleep disorders. 1, 2
Melatonin produces only a 9-minute reduction in sleep-onset latency with small improvements in sleep quality and minimal effect on wake after sleep onset or total sleep time when used as a hypnotic rather than as a circadian rhythm regulator. 1, 2
The American Academy of Sleep Medicine explicitly states that herbal supplements and nutritional substances, including melatonin, are not recommended for insomnia due to insufficient evidence of efficacy. 1
When Melatonin May Be Appropriate
Melatonin is primarily indicated for circadian rhythm sleep disorders (delayed sleep-wake phase disorder, jet lag, shift-work disorder, non-24-hour sleep-wake rhythm disorder) rather than acute insomnia. 2, 3, 4
Melatonin Dosing (If Used Despite Guideline Recommendations)
Standard Adult Dosing
Start with 3 mg of immediate-release melatonin taken 1.5–2 hours before desired bedtime. 2
If ineffective after 1–2 weeks, titrate in 3-mg increments up to a maximum of 15 mg. 2
Lower doses (0.5–5 mg) are as effective as higher doses; doses above 5 mg increase adverse effects without improving efficacy. 2
Elderly Patient Adjustments
No specific dose reduction is required for elderly patients based on age alone, as melatonin has a favorable safety profile in older adults. 2, 5
However, the American Academy of Sleep Medicine recommends avoiding melatonin for irregular sleep-wake rhythm disorder in older adults with dementia due to lack of benefit and potential for detrimental effects on mood and daytime functioning. 2
Hepatic Impairment Adjustments
No specific dosing adjustments for hepatic impairment are provided in the guidelines, as melatonin is primarily metabolized via CYP1A2 and has a short half-life (~20–50 minutes). 2, 3
Use caution in patients with severe liver disease, as melatonin clearance may be reduced, though clinical data are limited. 2
Safety Considerations
Common adverse effects include daytime sleepiness (1.66%), headache (0.74%), dizziness (0.74%), and nausea, which are more frequent at higher doses. 2
Melatonin is regulated as a dietary supplement in the U.S., raising concerns about purity and reliability of stated doses; choose United States Pharmacopeial Convention Verified formulations when possible. 2
Use with caution in patients taking warfarin due to potential interactions, and exercise caution in patients with epilepsy based on case reports. 2
Long-term safety data beyond 3–4 months are limited for chronic insomnia, though melatonin appears reasonably safe for ongoing treatment of circadian rhythm disorders. 2
Ramelteon as an Alternative
Ramelteon 8 mg is a superior alternative to melatonin for acute insomnia because it is FDA-approved, has a longer half-life, higher receptor affinity, and demonstrated efficacy in reducing sleep-onset latency without abuse potential or withdrawal symptoms. 1, 6, 7, 8
Ramelteon Advantages Over Melatonin
Ramelteon is a highly selective MT1/MT2 receptor agonist with substantially longer half-life (1–2.6 hours) compared with melatonin (~20–50 minutes), providing more sustained receptor activation. 3, 6, 7
Ramelteon reduces latency to persistent sleep by 10–19 minutes and increases total sleep time by 8–22 minutes in clinical trials, with no evidence of cognitive impairment, rebound insomnia, withdrawal effects, or abuse potential. 7
Ramelteon is not a DEA-scheduled controlled substance, making it appropriate for patients with substance use history or concerns about dependence. 1, 6
Ramelteon has a favorable safety profile with no hangover effects, no next-day cognitive impairment, and no tolerance development, unlike benzodiazepines or Z-drugs. 3, 6, 4, 8
Ramelteon Dosing
Standard dose: 8 mg taken within 30 minutes of bedtime, with at least 7 hours remaining before planned awakening. 1
No dose adjustment is required for elderly patients, as ramelteon has been successfully used in elderly insomniacs without adverse effects. 3, 7
Reduce dose in patients with severe hepatic impairment (no specific dose provided in guidelines, but caution is advised). 1
Ramelteon Limitations
Ramelteon primarily improves sleep-onset latency and is less effective for sleep-maintenance insomnia (wake after sleep onset, early-morning awakenings). 1, 7
For sleep-maintenance problems, low-dose doxepin 3–6 mg is preferred over ramelteon, as it specifically targets nocturnal awakenings. 1, 5
Common Pitfalls to Avoid
Do not use melatonin as first-line therapy for acute insomnia when FDA-approved hypnotics (ramelteon, eszopiclone, zolpidem, low-dose doxepin) have stronger evidence. 1, 2
Do not assume higher melatonin doses are more effective; doses above 5 mg increase side effects without added benefit due to receptor saturation. 2
Do not use melatonin in the morning or afternoon, as this worsens circadian misalignment. 2
Do not rely on melatonin for sleep maintenance, as it has minimal effect on wake after sleep onset or total sleep time. 1, 2
Do not prescribe melatonin without concurrent Cognitive Behavioral Therapy for Insomnia (CBT-I), which provides superior long-term outcomes. 1
Recommended First-Line Pharmacotherapy for Acute Insomnia
Instead of melatonin, use FDA-approved hypnotics with stronger evidence: