What are the medications used to treat sleep disturbances?

Medications for Sleep Disturbances

The primary medications used to treat sleep disturbances include benzodiazepine receptor agonists (BzRAs), melatonin receptor agonists, orexin receptor antagonists, sedating antidepressants, and other agents selected based on the specific sleep disorder being treated. 1

Classification of Sleep Disorders

Sleep disorders can be broadly categorized into:

• Insomnia: Difficulty falling asleep and/or maintaining sleep at least 3 times per week for at least 4 weeks, accompanied by distress 2
• Sleep disturbance and/or excessive sleepiness: Including obstructive sleep apnea (OSA), narcolepsy, and restless legs syndrome (RLS) 2

First-Line Pharmacological Options for Insomnia

Benzodiazepine Receptor Agonists (BzRAs)

• Eszopiclone (2-3 mg): Recommended for both sleep onset and maintenance insomnia 1, 3
• Zolpidem (5-10 mg): Effective for both sleep onset and maintenance insomnia; lower dose (5 mg) recommended for elderly patients 1, 4
• Zaleplon (10 mg): Specifically for sleep onset insomnia 1
• Temazepam (15 mg): For both sleep onset and maintenance insomnia 1

Melatonin Receptor Agonists

• Ramelteon (8 mg): Recommended for sleep onset insomnia 1

Second-Line Pharmacological Options

Sedating Antidepressants

• Doxepin (3-6 mg): Recommended for sleep maintenance insomnia 1
• Trazodone (25-100 mg): Often used despite limited recommendation in guidelines 2, 1
• Mirtazapine (7.5-30 mg): Used particularly when comorbid depression is present 2, 1

Orexin Receptor Antagonists

• Suvorexant: Recommended for sleep maintenance insomnia 1

Other Medications

• For Restless Legs Syndrome (RLS):

  • Dopamine agonists (ropinirole, pramipexole) 2
  • Gabapentin 2
  • Benzodiazepines 2
  • Opioids (in selected cases) 2

• For specific palliative care situations:

  • Olanzapine (2.5-5 mg) 2
  • Chlorpromazine (25-50 mg) 2
  • Quetiapine (2.5-5 mg) 2
  • Lorazepam (0.5-1 mg) 2

Not Recommended Agents

• Over-the-counter antihistamines (e.g., diphenhydramine): Lack of efficacy data and risk of side effects, particularly daytime sedation and delirium in older adults 2, 1
• Herbal supplements (e.g., valerian) and nutritional substances (e.g., melatonin): Insufficient evidence of efficacy for chronic insomnia 2, 1, 5
• Barbiturates and chloral hydrate: Not recommended due to safety concerns 2, 1
• Antipsychotics: Not recommended as first-line for insomnia due to metabolic side effects 2

Medication Selection Algorithm

1. Identify the specific sleep problem:

   • For sleep onset difficulty: Consider zaleplon, ramelteon, zolpidem, or eszopiclone 1
   • For sleep maintenance: Consider eszopiclone, zolpidem, temazepam, doxepin, or suvorexant 1

2. Consider patient-specific factors:

   • Elderly patients: Start with lower doses (e.g., zolpidem 5 mg) 1, 4
   • Comorbid depression/anxiety: Consider sedating antidepressants 1
   • Cancer patients: May require specific approaches including trazodone, olanzapine, or zolpidem 2

3. For specific sleep disorders:

   • Obstructive Sleep Apnea: CPAP, surgery, or oral appliances (not primarily medication) 2
   • Restless Legs Syndrome: Dopamine agonists, gabapentin, benzodiazepines, or opioids 2

Important Clinical Considerations

• Short-term use: Most sleep medications are approved for short-term use only 2, 1
• Lowest effective dose: Use the minimum effective dose for the shortest period possible 2
• Combination with non-pharmacological approaches: Medications should be used alongside cognitive behavioral therapy for insomnia (CBT-I) and sleep hygiene education 2, 1
• Regular reassessment: Periodic evaluation of continued need for medication 1

Common Pitfalls to Avoid

• Long-term use without reassessment: Most hypnotics are not intended for extended use 2, 1
• Failing to address underlying causes: Sleep disturbances may be secondary to other medical or psychiatric conditions 2
• Overlooking drug interactions: Many sleep medications have significant interaction potential 1
• Using sedating agents without considering their specific effects: Different medications target different aspects of sleep disturbance 1
• Using over-the-counter sleep aids with limited efficacy data: Many OTC products lack robust evidence 2, 1