Mirtazapine Dosing for Sleep Disturbances
For sleep disturbances, the recommended dose of mirtazapine is 7.5-15 mg administered orally once daily at bedtime.
Dosing Recommendations
- Starting dose: 7.5 mg at bedtime
- Effective dose range: 7.5-15 mg at bedtime
- Maximum dose: Generally not exceeding 15 mg when used primarily for sleep
- Timing: Administer in the evening prior to sleep
Mechanism for Sleep Improvement
Mirtazapine's effectiveness for sleep disturbances is based on its unique pharmacological profile:
- Antagonist of presynaptic alpha-2 adrenergic receptors
- Potent antagonist of postsynaptic 5-HT2 and 5-HT3 receptors 1
- Strong affinity for histamine H1 receptors, which contributes to its sedative effects
- Sedative effects are most pronounced at lower doses (7.5-15 mg) due to predominant histaminergic effects 2
Clinical Considerations
Patient Selection
Mirtazapine may be especially beneficial for:
- Patients with comorbid depression and sleep disturbances 3
- Patients with comorbid anorexia or weight loss 3
- Patients with refractory insomnia who haven't responded to first-line agents 3
Advantages
- Rapid onset of sleep effects (may improve sleep within the first week) 1
- Minimal anticholinergic effects compared to tricyclic antidepressants 2
- Low risk of sexual dysfunction compared to SSRIs 1
- Once-daily dosing due to 20-40 hour half-life 1
Common Side Effects
- Sedation (beneficial for sleep but may cause daytime drowsiness)
- Increased appetite
- Weight gain
- Dizziness 4
Important Considerations
Paradoxical effect: Higher doses (>15 mg) may actually be less sedating due to increased noradrenergic effects becoming more prominent than antihistaminic effects 2
FDA labeling: While the FDA-approved starting dose for depression is 15 mg 5, lower doses (7.5 mg) are commonly used off-label specifically for sleep 6
Monitoring: Assess effectiveness after 1-2 weeks; if inadequate response, consider dose adjustment
Duration: For chronic insomnia, reassess the need for continued treatment periodically
Discontinuation: Gradually taper rather than abruptly stopping to avoid withdrawal symptoms 5
Alternative Options
If mirtazapine is ineffective or not tolerated, consider other options for insomnia per guidelines:
- Eszopiclone, zolpidem, or zaleplon for sleep onset/maintenance issues
- Doxepin (3-6 mg) for sleep maintenance issues
- Ramelteon for sleep onset issues 3
Remember that mirtazapine is not FDA-approved specifically for insomnia but is used off-label for this purpose, particularly when patients have comorbid depression or when other sleep medications have failed.