Mirtazapine Dosage and Treatment Plan for Major Depressive Disorder
The recommended dosage for mirtazapine in major depressive disorder starts at 15 mg once daily in the evening, with gradual increases up to a maximum of 45 mg daily based on clinical response, with dose adjustments made at 1-2 week intervals to allow proper evaluation of therapeutic effects. 1
Initial Dosing and Titration
- Start with 15 mg once daily, administered in the evening prior to sleep 1
- After 1-2 weeks, if clinical response is inadequate, increase dose to 30 mg once daily 1, 2
- Further dose increases up to 45 mg daily can be made if needed, but should not occur at intervals less than 1-2 weeks to allow proper evaluation of response 1, 3
- Once-daily evening dosing is appropriate due to mirtazapine's 20-40 hour elimination half-life 3
Duration of Treatment
- For a first episode of major depression, continue treatment for 4-9 months after achieving a satisfactory response 4
- For patients with two or more previous depressive episodes, longer treatment duration may be beneficial 4
- After 9 months of treatment, consider gradual dose reduction to reassess the need for continued medication 4
Special Populations
- For elderly or debilitated patients, start with 7.5 mg at bedtime 4
- In patients with hepatic or renal impairment, careful dose titration and close monitoring for adverse effects is recommended 2
Monitoring and Follow-up
- Assess patient status, therapeutic response, and adverse effects regularly, beginning within 1-2 weeks of treatment initiation 4
- If adequate response is not achieved within 6-8 weeks, modify treatment approach 4
- Monitor for early improvement in symptoms, as mirtazapine may show onset of action as early as 1-2 weeks 5
Discontinuation
- When discontinuing mirtazapine, gradually reduce the dosage rather than stopping abruptly to minimize withdrawal symptoms 1
- Taper over 10-14 days to limit withdrawal symptoms 4
Clinical Considerations
- Mirtazapine is particularly effective for patients with depression accompanied by insomnia, anxiety, or poor appetite 4
- The medication promotes sleep, appetite, and weight gain, making it especially useful for patients with insomnia and anorexia 4
- At lower doses (15 mg), mirtazapine tends to be more sedating due to greater H1 receptor antagonism; at higher doses (30-45 mg), noradrenergic effects become more prominent 5
- Screen for bipolar disorder prior to initiating treatment 1
Common Side Effects
- Most common adverse effects include somnolence, increased appetite, weight gain, and dizziness 6
- Sedation is often more pronounced at lower doses and may diminish at therapeutic doses (≥15 mg) 3
- Mirtazapine has minimal anticholinergic effects and sexual dysfunction compared to other antidepressants 3, 2
- Monitor for rare but serious adverse effects such as agranulocytosis and neutropenia 3
Drug Interactions
- Allow at least 14 days between discontinuing MAOIs and starting mirtazapine, and vice versa 1
- Dose adjustments may be needed with concomitant use of strong CYP3A inducers or inhibitors 1
- Mirtazapine has less effect on the metabolism of other medications compared to many other antidepressants 3
Mirtazapine's unique mechanism as a noradrenergic and specific serotonergic antidepressant (NaSSA) provides effective treatment for major depressive disorder with a favorable side effect profile for patients troubled by insomnia, anxiety, or poor appetite.