Mirtazapine Treatment Regimen for Major Depressive Disorder
Mirtazapine should be initiated at 15 mg once daily at bedtime, titrated to 30 mg after 4 days if tolerated, with a maximum effective dose of 45 mg daily for the treatment of major depressive disorder. 1, 2
Dosing Protocol
- Initial dose: 15 mg once daily at bedtime for 4 days
- Titration: Increase to 30 mg daily for 10 days
- Maintenance:
- Continue at 30 mg if effective
- If insufficient improvement, increase to maximum dose of 45 mg daily
- Duration: Continue treatment for at least 4-9 months after achieving remission 2
Efficacy Evidence
Mirtazapine's efficacy for major depressive disorder has been established in multiple placebo-controlled trials:
- FDA-approved based on 4 placebo-controlled, 6-week trials in adult outpatients with major depressive disorder 1
- Mean effective dose in clinical trials ranged from 21-32 mg/day 1
- Shows superior efficacy over placebo on multiple depression rating scales:
- Hamilton Depression Rating Scale (HDRS)
- Clinical Global Impression (CGI) Severity score
- Montgomery and Asberg Depression Rating Scale (MADRS) 1
Clinical Advantages
Mirtazapine offers several unique benefits that may guide treatment selection:
- Rapid onset of action: May work faster than SSRIs 2, 3
- Sleep improvement: Particularly beneficial for patients with depression-related insomnia 4, 2
- Anxiolytic effects: Effective for depression with anxiety symptoms 3, 5
- Low sexual dysfunction risk: Unlike many other antidepressants 6
- Minimal drug interactions: Limited CYP450 interactions compared to some antidepressants 5
Common Side Effects
- Sedation/somnolence: Most common side effect (23% vs. 14% with placebo) 7
- Increased appetite/weight gain: Reported in approximately 10-11% of patients 7, 2
- Dry mouth: Occurs in about 25% of patients 7
Special Populations
- Elderly patients: Start at lower doses and titrate more slowly
- Hepatic/renal impairment: Careful dosage titration with regular monitoring 7
- Patients with insomnia: Mirtazapine 7.5-30 mg at bedtime is specifically recommended for insomnia in depressed patients 4, 2
Monitoring Recommendations
- Assess response using standardized measures (e.g., PHQ-9) every 2-4 weeks 2
- Allow adequate trial duration (6-8 weeks) before determining efficacy 2
- Monitor for suicidal ideation, particularly during initial treatment phase
- Watch for rare but serious adverse effects such as agranulocytosis or neutropenia 7
Treatment Resistance Considerations
If inadequate response after 6-8 weeks at maximum tolerated dose:
- Consider switching to another antidepressant class
- Consider augmentation strategies (e.g., with atypical antipsychotics)
- Evaluate for treatment-resistant depression if failing two adequate trials 2
Mirtazapine's unique pharmacological profile makes it particularly suitable for patients with depression accompanied by insomnia, anxiety, or poor appetite, and in those who cannot tolerate sexual dysfunction from other antidepressants.