Non-Narcotic Sleep Medications
The American Academy of Sleep Medicine recommends benzodiazepine receptor agonists (BzRAs) such as eszopiclone, zolpidem, and zaleplon, along with the melatonin receptor agonist ramelteon, as first-line pharmacologic treatments for insomnia—none of these are narcotics (opioids). 1
First-Line Non-Narcotic Options
Benzodiazepine Receptor Agonists (Non-Benzodiazepine "Z-drugs")
These medications work on GABA receptors but are not classified as narcotics:
Eszopiclone (2-3 mg): Effective for both sleep onset and sleep maintenance insomnia, with a longer half-life that improves total sleep time by 28-57 minutes compared to placebo 1, 2
Zolpidem (10 mg): Treats both sleep onset and maintenance insomnia, though lower doses (5 mg) are recommended for elderly patients to minimize fall risk 1, 3
Zaleplon (10 mg): Very short half-life makes it ideal for sleep onset insomnia with minimal next-day residual effects, as it is unlikely to cause morning sedation 1
Melatonin Receptor Agonist
Ramelteon (8 mg): Works on melatonin receptors rather than GABA systems, making it particularly suitable for patients with substance use disorder history since it has no DEA scheduling and no dependence potential 1, 4
Ramelteon demonstrates reduced sleep latency in controlled trials and is specifically effective for sleep onset difficulties with no tolerance development 4, 5
Second-Line Non-Narcotic Options
Benzodiazepines (Not Narcotics, but Controlled Substances)
Temazepam (15 mg): Intermediate-acting benzodiazepine for both sleep onset and maintenance, though it carries higher risks of tolerance and dependence compared to Z-drugs 1
Triazolam (0.25 mg): Short-acting option for sleep onset, but associated with rebound anxiety and not considered first-line 1
Orexin Receptor Antagonist
Suvorexant (10-20 mg): Blocks the orexin pathway that promotes wakefulness, effective for sleep maintenance insomnia with less motor impairment than GABA-acting drugs 1, 6
This class shows no dependence or tolerance-inducing effects, making them viable for longer-term treatment 6
Low-Dose Antidepressant
Doxepin (3-6 mg): At low doses, works primarily as an H1 histamine antagonist rather than through antidepressant mechanisms, specifically effective for sleep maintenance insomnia with minimal anticholinergic effects 1, 2, 7
Improves total sleep time by 26-32 minutes and reduces wake after sleep onset by 22-23 minutes 2
Medications NOT Recommended
The American Academy of Sleep Medicine explicitly recommends against the following non-narcotic agents due to insufficient evidence or unfavorable risk-benefit profiles:
Trazodone (50 mg): Despite widespread off-label use, lacks robust efficacy data for primary insomnia 1, 8
Diphenhydramine: Over-the-counter antihistamine with anticholinergic side effects, particularly problematic in elderly patients 1
Melatonin supplements (2 mg): Insufficient evidence for treating insomnia, though the prescription melatonin agonist ramelteon is effective 1, 5
Valerian and L-tryptophan: Herbal supplements with inadequate evidence for efficacy 1
Critical Selection Factors
Symptom pattern determines medication choice:
Sleep onset only: Zaleplon or ramelteon (very short half-lives prevent morning sedation) 1
Sleep maintenance: Eszopiclone, temazepam, doxepin, or suvorexant (longer duration of action) 1, 2
Both onset and maintenance: Zolpidem or eszopiclone 1
Special populations require dose adjustments:
Elderly patients need lower doses of all sleep medications due to increased sensitivity and fall risk 3, 2
Patients with substance use history should preferentially receive ramelteon (non-scheduled) or suvorexant (lower abuse potential) 1, 3
Liver disease requires dose reduction, particularly for medications with hepatic metabolism 1
Important Safety Considerations
All BzRAs carry FDA warnings about complex sleep behaviors including sleep-walking, sleep-driving, and sleep-eating that patients may not remember 9
Patients must be counseled to:
- Take medication only when able to remain in bed for 7-8 hours 9
- Avoid alcohol and other CNS depressants 9, 8
- Not take medication after a meal, which delays absorption 9
Common pitfall: Combining multiple sedative medications increases risk of cognitive impairment, falls, and complex sleep behaviors without improving efficacy 7
Non-Pharmacologic Foundation
Cognitive Behavioral Therapy for Insomnia (CBT-I) should be considered first-line treatment before or alongside pharmacotherapy, as it provides sustained improvement without tolerance issues 1, 2, 7, 10