Mirtazapine Dosage and Treatment Approach for Major Depressive Disorder
The recommended starting dose of mirtazapine for major depressive disorder is 15 mg once daily administered orally in the evening prior to sleep, with gradual titration up to 45 mg per day based on clinical response and tolerability. 1
Dosing Guidelines
Initial Dosing and Titration
- Start with 15 mg once daily, preferably in the evening before bedtime 1
- Dose adjustments should not be made in intervals of less than 1-2 weeks to allow sufficient time for evaluation of response 1
- If patients do not have an adequate response to the initial 15 mg dose, increase the dose gradually:
- Week 1-2: 15 mg daily
- Week 3-4: 30 mg daily (if needed)
- Week 5+: 45 mg daily (maximum dose, if needed) 1
Special Populations
- Elderly or debilitated patients: Start with lower doses (15 mg) and titrate more slowly 2
- Patients with hepatic or renal impairment: Careful dosage titration with regular monitoring for adverse events 3
Efficacy and Treatment Response
- Improvement in depressive symptoms is typically observed within the first 1-2 weeks of treatment 4
- Full therapeutic effect is generally achieved at 4-6 weeks of treatment 4
- Long-term studies at 40 weeks show continued improvements in response rates and lower relapse rates compared to placebo 4
Treatment Duration
- For first episode of depression: Continue treatment for 4-9 months after achieving remission 2
- For recurrent depression: Consider maintenance treatment for 1+ years 2
- Regular monitoring is essential, especially in the first 1-2 weeks of treatment to assess therapeutic response and monitor for side effects 2
Common Side Effects
The most common side effects of mirtazapine include:
Important Note on Sedation
- Sedation is most pronounced at lower doses (15 mg) due to higher H1 receptor occupancy 4
- Paradoxically, sedation may decrease at higher doses (30-45 mg) as noradrenergic effects become more prominent 7
- Consider this property when timing administration (evening dosing is preferred) 1
Pharmacological Profile
Mirtazapine has a unique mechanism of action:
- Enhances norepinephrine and serotonin neurotransmission by blocking alpha-2 presynaptic adrenoceptors 4
- Antagonizes 5-HT2 and 5-HT3 receptors, which reduces serotonin-related side effects like nausea and sexual dysfunction 4
- Has strong antihistaminic properties (H1 receptor antagonism), contributing to its sedative effects 4
Clinical Considerations and Advantages
Mirtazapine is particularly useful for patients with:
Mirtazapine may be especially effective in patients with depression and anorexia 6
Drug Interactions and Precautions
- Screen for bipolar disorder prior to initiating treatment 1
- Allow at least 14 days between discontinuing MAOIs and starting mirtazapine, and vice versa 1
- Dose adjustments may be needed with:
Discontinuation
- Gradually reduce the dosage rather than stopping abruptly to minimize withdrawal symptoms 1
- Taper over several weeks, especially for patients on higher doses or with longer treatment duration
Monitoring
- Monitor for therapeutic response beginning within 1-2 weeks of starting treatment 2
- Assess for side effects, particularly sedation, weight gain, and rare but serious effects like agranulocytosis 3
- Monitor for emergence of suicidal thoughts, especially in the first 1-2 months of treatment 2
Mirtazapine has demonstrated efficacy comparable to tricyclic antidepressants and may have a more rapid onset of action than SSRIs, making it a valuable option in the treatment of major depressive disorder, particularly when sleep disturbance, anxiety, or appetite/weight loss are prominent symptoms 8.