Recommended Dosing of Mirtazapine for Insomnia
For insomnia treatment, mirtazapine should be administered at a dose of 7.5-15 mg once daily at bedtime. This lower dose range is most effective for insomnia due to mirtazapine's sedating properties, which are actually more pronounced at lower doses 1, 2.
Dosing Rationale and Mechanism
Mirtazapine's sedative effects are primarily mediated through:
- Potent antagonism of histamine H1 receptors
- Blockade of 5-HT2A and 5-HT2C serotonin receptors
- These sedating effects are more prominent at lower doses (7.5-15 mg)
At higher doses (30-45 mg), mirtazapine's noradrenergic effects become more dominant, which can actually reduce the sedative properties 3, 4.
Dosing Algorithm for Insomnia
Initial dose: Start with 7.5 mg (half of a 15 mg tablet) once daily at bedtime 5
- This lower dose maximizes the sedative effect while minimizing side effects
Titration: If inadequate response after 1-2 weeks, increase to 15 mg once daily at bedtime 2
- Do not increase beyond 15 mg if the primary goal is treating insomnia
- Higher doses (>15 mg) may reduce sedative effects due to increased noradrenergic activity
Administration timing: Administer 30-60 minutes before desired sleep time 2, 3
Clinical Considerations
- Onset of action: Sleep improvements may be observed within the first week of treatment 3, 4
- Advantages over other sleep medications:
- No significant tolerance development to sedative effects
- No rebound insomnia upon discontinuation
- Promotes sleep without disrupting sleep architecture
Side Effects to Monitor
- Common side effects: Increased appetite, weight gain, dry mouth, dizziness 3, 6
- Monitoring: Weight should be monitored regularly, especially in patients concerned about weight gain
- Caution: May cause daytime sedation in some patients; assess for morning drowsiness
Important Caveats
- While the FDA label for mirtazapine indicates a starting dose of 15 mg for depression 2, lower doses (7.5 mg) are commonly used off-label for insomnia 5
- Mirtazapine is not FDA-approved specifically for insomnia treatment
- The American Academy of Sleep Medicine does not specifically recommend mirtazapine in their insomnia guidelines, focusing instead on other agents 1
- For patients with both depression and insomnia, mirtazapine may be especially beneficial at doses of 15-30 mg 1
Drug Interactions
- Avoid concurrent use with MAOIs (allow 14 days between stopping one and starting the other) 2
- Dose adjustments may be needed with:
- Strong CYP3A inducers (may need to increase mirtazapine dose)
- Strong CYP3A inhibitors (may need to decrease mirtazapine dose)
- Cimetidine (may need to decrease mirtazapine dose) 2
By following this dosing approach, mirtazapine can be an effective option for treating insomnia, particularly in patients who may also have depressive symptoms or who have not responded to first-line insomnia treatments.