What is the recommended use and dosage of Mirtazapine (Remeron) for treating major depressive disorder?

Mirtazapine for Major Depressive Disorder: Dosage and Recommendations

The recommended treatment regimen for mirtazapine in major depressive disorder is to start with 15 mg once daily administered orally in the evening prior to sleep, with gradual titration up to 45 mg daily as needed for clinical response. 1

Dosing Guidelines

• Initial dose: 15 mg once daily, preferably in the evening before sleep 1
• Titration: Dose increases should not be made in intervals of less than 1-2 weeks to allow sufficient time for evaluation of response 1
• Maximum dose: 45 mg per day 1
• Alternative starting dose: Some patients may benefit from starting at 7.5-15 mg at bedtime, particularly elderly patients or those sensitive to sedative effects 2

Clinical Efficacy

Mirtazapine has demonstrated efficacy in treating major depressive disorder comparable to:

• Tricyclic antidepressants (amitriptyline, clomipramine, doxepin) 3, 4
• SSRIs (fluoxetine, paroxetine, citalopram) 3, 5

A notable advantage of mirtazapine is its faster onset of action compared to SSRIs:

• Studies show statistically significantly faster onset of action than citalopram, fluoxetine, paroxetine, or sertraline 6, 2
• Initial effects may be seen within 1-2 weeks, though most response rates become similar after 4 weeks 6

Mechanism of Action and Clinical Implications

Mirtazapine works through a dual mechanism as a noradrenergic and specific serotonergic antidepressant (NaSSA):

• Blocks presynaptic alpha-2 adrenergic receptors 7, 8
• Blocks postsynaptic serotonin type 2 and type 3 receptors 7, 8
• Increases both noradrenergic and specific serotonergic neurotransmission 8, 5

Side Effect Profile

The most common side effects include:

1. Somnolence/sedation (most common) 7, 4
2. Increased appetite 7, 3
3. Weight gain 7, 3
4. Dizziness 7

Important clinical considerations:

• Sedation tends to be more prominent at lower doses (15 mg) and may decrease at higher doses 4
• Unlike SSRIs, mirtazapine has minimal sexual dysfunction side effects 3, 4
• Minimal anticholinergic and cardiovascular effects 8

Special Populations and Considerations

Elderly Patients

• Consider starting at lower doses (7.5-15 mg)
• Steady-state concentrations take longer to achieve in elderly patients (6 days vs. 4 days in younger adults) 5

Drug Interactions

• Screen for bipolar disorder prior to starting mirtazapine 1
• Allow at least 14 days between discontinuing MAOIs and starting mirtazapine (and vice versa) 1
• Dose adjustments may be needed with:
  • Strong CYP3A inducers (carbamazepine, phenytoin, rifampin) - may need increased mirtazapine dose 1
  • Strong CYP3A inhibitors (ketoconazole, clarithromycin) - may need decreased mirtazapine dose 1
  • Cimetidine - may need decreased mirtazapine dose 1

Discontinuation

• Gradually taper mirtazapine rather than stopping abruptly to minimize discontinuation symptoms 1

Additional Benefits

• May be particularly beneficial for patients with:
  • Comorbid insomnia (due to sedative effects) 6, 3
  • Anxiety symptoms 7, 3, 5
  • Poor appetite or weight loss 2, 4

Mirtazapine can also be considered as an alternative for patients who have failed or cannot tolerate SSRIs, particularly when sexual dysfunction is a concern 3, 4.