Mirtazapine for Major Depressive Disorder
Recommended Dosage
Start mirtazapine at 15 mg once daily, preferably in the evening before sleep, and increase up to a maximum of 45 mg daily if needed, with dose changes made no more frequently than every 1-2 weeks. 1
Dosing Algorithm
- Initial dose: 15 mg once daily at bedtime 1
- Dose titration: If inadequate response after 6-8 weeks, increase dose up to maximum 45 mg daily 2, 1
- Timing of dose changes: Wait at least 1-2 weeks between adjustments to allow adequate evaluation of response 1
- Effective range: 15-45 mg daily 3, 1, 4
Monitoring Timeline
Begin assessing therapeutic response and adverse effects within 1-2 weeks of starting treatment, with particular attention to suicidal ideation during this early period. 3, 2
- Week 1-2: Initial assessment for early response (sleep and anxiety symptoms may improve first), monitor for suicidal thoughts, agitation, or unusual behavioral changes 3, 2, 5
- Week 6-8: If inadequate response by this point, modify treatment 3, 2
- Week 2-4: Full antidepressant effect typically achieved 5, 4
Duration of Treatment
Continue mirtazapine for 4-9 months after achieving satisfactory response in first-episode depression; patients with 2 or more prior episodes require longer maintenance therapy. 3, 2
- First episode: 4-9 months continuation after remission 3, 2
- Recurrent depression (≥2 episodes): Extended maintenance therapy beyond 9 months 3, 2
- Discontinuation: Taper gradually rather than stopping abruptly to minimize withdrawal symptoms 1
Clinical Advantages
Mirtazapine is particularly suitable for patients with depression accompanied by insomnia, anxiety, anorexia, or weight loss due to its sedating properties and appetite-stimulating effects. 2
- Faster onset: More rapid action than fluoxetine, paroxetine, and sertraline for some symptoms 2
- Sleep benefits: Improves sleep disturbances within the first week, before full antidepressant effect 2, 5
- Appetite stimulation: Promotes weight gain, making it ideal for depressed patients with anorexia 2
- Preferred agent: Considered a first-line option alongside SSRIs and SNRIs due to favorable adverse effect profile 3
Common Adverse Effects to Monitor
- Most common: Somnolence/sedation, increased appetite, weight gain 2, 1, 4
- Other effects: Dry mouth, constipation or diarrhea, dizziness 3, 2, 4
- Less common than SSRIs: Minimal sexual dysfunction, gastrointestinal symptoms, or insomnia compared to SSRIs 5
- Cardiovascular: Minimal cardiovascular and anticholinergic effects 5
Important Dosage Modifications
Reduce mirtazapine dose when co-administered with strong CYP3A4 inhibitors (ketoconazole, clarithromycin) or cimetidine; increase dose with strong CYP3A inducers (carbamazepine, phenytoin, rifampin). 1
Critical Safety Considerations
- Screen for bipolar disorder: Assess personal and family history before initiating treatment 1
- MAOI interactions: Allow 14 days between discontinuing an MAOI and starting mirtazapine, and vice versa 1
- Suicide risk: Highest during first 1-2 months of treatment; monitor closely for worsening depression, agitation, or suicidal thoughts 3
When to Modify Treatment
If no adequate response within 6-8 weeks at appropriate doses, switch to an SSRI or SNRI, or add another antidepressant with a different mechanism of action. 3, 2