What medications are appropriate for insomnia?

Appropriate Medications for Insomnia

For chronic insomnia, use short-to-intermediate acting benzodiazepine receptor agonists (zolpidem 10 mg, eszopiclone 2-3 mg, zaleplon 10 mg, or temazepam 15 mg) or ramelteon 8 mg as first-line pharmacological agents, selecting based on whether the patient has sleep onset versus sleep maintenance problems. 1, 2

First-Line Pharmacological Treatment Algorithm

For Sleep Onset Insomnia (Difficulty Falling Asleep)

• Zaleplon 10 mg - shortest-acting option, ideal when only sleep initiation is problematic and at least 4 hours remain for sleep 1, 2
• Zolpidem 10 mg - effective for sleep onset with short-to-intermediate duration 1, 3
• Ramelteon 8 mg - melatonin receptor agonist with minimal cognitive risk, no GABA effects, particularly appropriate for patients concerned about dependence or cognitive side effects 1, 2, 4
• Triazolam 0.25 mg (0.125 mg in elderly) - traditional benzodiazepine option with short action 1

For Sleep Maintenance Insomnia (Difficulty Staying Asleep)

• Eszopiclone 2-3 mg - demonstrated efficacy for sleep maintenance with no short-term usage restrictions, reduces wake after sleep onset by 22-50 minutes 1, 2, 5
• Zolpidem 10 mg - effective for both onset and maintenance 1, 3
• Temazepam 15-30 mg (7.5 mg in elderly) - traditional benzodiazepine with intermediate duration 1, 2
• Suvorexant (orexin receptor antagonist) - specifically for sleep maintenance, reduces wake time after sleep onset by 16-28 minutes 1, 6
• Doxepin 3-6 mg - low-dose formulation specifically for sleep maintenance 1, 2

For Both Sleep Onset and Maintenance

• Eszopiclone 2-3 mg - most versatile option with long-term efficacy data up to 12 months without tolerance 1, 5, 7
• Zolpidem 10 mg - demonstrated superiority over placebo for both sleep latency and efficiency 1, 3
• Temazepam 15 mg - traditional option effective for both components 1, 2

Second-Line Approach When First-Line Fails

• Try an alternate agent from the same class (different BzRA or switch between BzRA and ramelteon) before moving to other drug categories 1, 2
• Consider sedating antidepressants only when:
  • Comorbid depression or anxiety is present 1, 2
  • Multiple first-line agents have failed 1
  • Patient has treatment-resistant insomnia 1

Sedating Antidepressant Options (Second-Line)

• Trazodone - has minimal anticholinergic activity but the American Academy of Sleep Medicine recommends against its use based on 50 mg dose trials, despite widespread clinical use 1
• Mirtazapine - associated with weight gain, consider when appetite stimulation is desired 1
• Doxepin (higher doses than 3-6 mg), amitriptyline, trimipramine - have anticholinergic effects, use cautiously in elderly 1

Important caveat: Low-dose sedating antidepressants do not constitute adequate treatment for major depression; full antidepressant doses are required for comorbid depression 1

Medications Explicitly NOT Recommended

The American Academy of Sleep Medicine provides strong guidance against several commonly used agents:

• Diphenhydramine (OTC antihistamine) - anticholinergic effects, lack of efficacy data, safety concerns especially in elderly 1, 2, 8
• Melatonin 2 mg - insufficient evidence for efficacy 1, 2, 8
• Trazodone 50 mg - negative recommendation despite common clinical use 1, 8
• Valerian and herbal supplements - lack efficacy and safety data 1, 8
• Tiagabine 4 mg - insufficient benefit 1
• L-tryptophan 250 mg - insufficient benefit 1, 8
• Barbiturates and chloral hydrate - unacceptable safety profiles 1, 8

Critical Safety Considerations

Cognitive and Dependence Risks

• All benzodiazepines and Z-drugs act on GABA receptors and carry risks of amnesia, cognitive impairment, and potential contribution to dementia with long-term use 2
• Ramelteon has minimal cognitive risk as it works via melatonin receptors without affecting GABA 2, 4
• Use the lowest effective dose for the shortest necessary duration 2

Behavioral Side Effects Warning

• BzRA hypnotics (zolpidem, eszopiclone, zaleplon) have been associated with complex sleep-related behaviors including sleepwalking, sleep-eating, sleep-driving, and sexual behavior 1
• Patients must be cautioned about allowing appropriate sleep time, using only prescribed doses, and avoiding combination with alcohol or other sedatives 1

Dosing Adjustments Required

• Elderly patients: Reduce doses (zolpidem 5 mg, temazepam 7.5 mg, triazolam 0.125 mg, eszopiclone 1 mg) 1
• Hepatic impairment: Reduce eszopiclone to maximum 2 mg, zolpidem to 5 mg 1
• Avoid in pregnancy, nursing, compromised respiratory function (asthma, COPD, sleep apnea), or hepatic heart failure 1

Prescribing Strategy to Minimize Dependence

• Consider intermittent dosing (e.g., three nights per week) rather than nightly use 2, 8
• Use as-needed dosing when appropriate to reduce tolerance 2
• Follow patients every few weeks initially to assess effectiveness, side effects, and ongoing need 2, 8
• Taper medication when conditions allow, ideally with concurrent cognitive behavioral therapy for insomnia (CBT-I) to facilitate successful discontinuation 2
• Long-term use may be indicated for severe/refractory insomnia or chronic comorbid illness, but requires consistent monitoring 2

Administration Guidance

• Take on an empty stomach to maximize effectiveness 1
• Avoid concomitant CNS depressants and alcohol due to additive psychomotor impairment 1
• Rapid dose decrease or abrupt discontinuation of benzodiazepines can produce withdrawal symptoms including rebound insomnia 1
• Reevaluate if insomnia persists after 7-10 days to rule out comorbid conditions 6

Patient Education Requirements

All pharmacological treatment must include education about: 2, 8

• Treatment goals and realistic expectations
• Safety concerns and potential side effects
• Drug interactions
• Availability of cognitive-behavioral treatments (CBT-I as first-line)
• Risk of dosage escalation
• Potential for rebound insomnia upon discontinuation