Mirtazapine Dosing for Insomnia
For insomnia treatment, mirtazapine should be administered at a dose of 7.5-15 mg once daily, taken orally in the evening prior to sleep. This lower dosage range is more effective for sleep than higher doses due to mirtazapine's unique pharmacological profile.
Dosing Recommendations
- Starting dose: 7.5 mg once daily at bedtime
- Effective dose range: 7.5-15 mg once daily
- Administration timing: Evening, prior to sleep
Dose-Response Relationship
- At lower doses (7.5-15 mg), mirtazapine's histamine H1 receptor antagonism predominates, producing sedation beneficial for insomnia 1, 2
- At higher doses (30-45 mg), noradrenergic effects become more prominent, which may actually reduce sedation and be less effective for insomnia 1
- The FDA-approved starting dose for depression is 15 mg, but lower doses are often more appropriate specifically for insomnia 3
Evidence Supporting Low-Dose Use
The MIRAGE study, a recent randomized controlled trial in older adults with chronic insomnia, demonstrated that mirtazapine 7.5 mg was superior to placebo in reducing insomnia severity 4. After 28 days of treatment:
- Mean reduction in Insomnia Severity Index: -6.5 points with mirtazapine vs -2.9 points with placebo (p=0.003)
- Improvements in wake after sleep onset, total sleep time, and sleep efficiency
Pharmacological Considerations
Mirtazapine has several mechanisms that contribute to its sleep-promoting effects:
- Potent antagonism of histamine H1 receptors (sedative effect)
- Blockade of serotonin 5-HT2 and 5-HT3 receptors (reduces insomnia and anxiety)
- Alpha-2 adrenergic receptor antagonism (enhances noradrenergic and serotonergic neurotransmission) 1, 2
The elimination half-life of mirtazapine is approximately 20-40 hours, making it suitable for once-daily dosing at bedtime 1.
Clinical Pearls and Precautions
- Sleep onset effects: Sedation typically occurs within the first week of treatment 1
- Common side effects: Drowsiness (23%), dry mouth (25%), increased appetite (11%), and weight gain (10%) 2
- Monitoring: Follow up within 7-10 days of initiating treatment to assess response and side effects 5
- Dose adjustment: If needed, dose changes should not be made in intervals of less than 1-2 weeks 3
- Discontinuation: Gradually taper rather than abruptly stopping to prevent withdrawal symptoms 3
Alternative Options
Current guidelines from the American Academy of Sleep Medicine recommend several other medications as first-line pharmacological treatments for insomnia before considering mirtazapine 5:
- For sleep onset insomnia: zolpidem (5-10 mg), zaleplon (10 mg), or ramelteon (8 mg)
- For sleep maintenance insomnia: eszopiclone (2-3 mg), doxepin (3-6 mg), or suvorexant (10-20 mg)
Cognitive behavioral therapy for insomnia (CBT-I) remains the recommended first-line treatment for chronic insomnia before considering any medication 5.