What is the optimal dose of mirtazapine (Remeron) for treating insomnia?

Optimal Dose of Mirtazapine for Sleep

For treating insomnia, the optimal dose of mirtazapine is 7.5-15 mg taken orally at bedtime, with lower doses (7.5 mg) being more sedating than higher doses. 1, 2

Dosing Considerations

• Mirtazapine is used off-label for insomnia at lower doses than those used for depression 3
• The FDA-approved starting dose for mirtazapine is 15 mg once daily, preferably in the evening prior to sleep 1
• For insomnia treatment specifically:
  • 7.5 mg is often the most sedating dose due to predominant histamine H1 receptor blockade at lower doses 2
  • At higher doses (>15 mg), the sedative effect may diminish as noradrenergic effects become more prominent 4, 2

Evidence for Efficacy

• Mirtazapine has been shown to improve sleep quality and duration when used at low doses 3, 5
• A recent randomized controlled trial in older adults found that mirtazapine 7.5 mg significantly reduced insomnia severity compared to placebo after 28 days of treatment 5
• The sedative properties of mirtazapine are primarily attributed to:
  • Antagonism of histamine H1 receptors 4
  • Blockade of 5-HT2A and 5-HT2C serotonin receptors 4, 2
  • Indirect enhancement of serotonergic neurotransmission 4

Clinical Considerations

• Mirtazapine's sedative effects typically occur within the first week of treatment 4, 6
• Administration on an empty stomach is advised to maximize effectiveness 3
• Potential advantages over benzodiazepines and Z-drugs:
  • Non-scheduled medication (not controlled substance) 3
  • Less risk of dependence or withdrawal 6
  • May have additional benefits for patients with comorbid depression 2

Important Precautions

• Mirtazapine is not FDA-approved specifically for insomnia treatment 3
• Common side effects include:
  • Increased appetite and weight gain 4, 6
  • Daytime sedation (especially at lower doses) 4, 2
  • Dizziness 6
  • Transient elevations in cholesterol levels and liver function tests 4
• Caution is advised in:
  • Elderly patients (may require lower doses) 3
  • Patients with hepatic or renal impairment (may affect clearance) 1, 6
  • Patients taking CYP3A inhibitors or inducers (may require dose adjustments) 1

Alternative Options for Insomnia

• Current guidelines suggest the following FDA-approved medications for insomnia:
  • Eszopiclone (2-3 mg) for sleep onset and maintenance insomnia 3
  • Zolpidem (10 mg) for sleep onset and maintenance insomnia 3
  • Doxepin (3-6 mg) for sleep maintenance insomnia 3
  • Suvorexant (10-20 mg) for sleep maintenance insomnia 3
  • Ramelteon (8 mg) for sleep onset insomnia 3

Summary of Dosing Algorithm

1. Start with 7.5 mg (half of a 15 mg tablet) at bedtime for maximum sedative effect 2, 5
2. If ineffective after 1-2 weeks, may increase to 15 mg at bedtime 1, 2
3. Do not exceed 15 mg when using specifically for insomnia 2
4. Take approximately 30-60 minutes before desired sleep time 3
5. Monitor for side effects, particularly daytime sedation and weight gain 4, 6