What is the recommended dosage and treatment regimen for Mirtazapine (Remeron) in patients with major depressive disorder?

Mirtazapine Dosage and Treatment Regimen for Major Depressive Disorder

For patients with major depressive disorder, mirtazapine should be initiated at 15 mg once daily at bedtime, with titration up to 45 mg daily as needed for clinical response, maintaining each dose for 1-2 weeks before adjusting. 1

Initial Dosing and Titration

The FDA-approved dosing regimen for mirtazapine follows a clear protocol:

• Starting dose: 15 mg once daily, administered orally in the evening before sleep 1
• Titration: If inadequate response occurs, increase dose in intervals of 1-2 weeks
• Maximum dose: 45 mg per day 1
• Administration timing: Preferably in the evening due to sedative effects

This evening administration timing takes advantage of mirtazapine's sedative properties, which can help address the sleep disturbances commonly associated with depression 2.

Efficacy Considerations

Mirtazapine demonstrates several important clinical characteristics:

• Onset of action: May have a faster onset (2-4 weeks) compared to some SSRIs, with sleep disturbances and anxiety potentially improving within the first week 3
• Efficacy profile: Comparable efficacy to tricyclic antidepressants but with a more favorable side effect profile 4
• Therapeutic response: Requires 4-8 weeks for full therapeutic trial 2

Dose-Response Relationship

Clinical evidence suggests that higher doses may provide different therapeutic effects:

• Lower doses (15 mg): More sedating due to predominant histamine H1 receptor blockade
• Higher doses (30-45 mg): May have more noradrenergic and serotonergic effects, potentially reducing the sedative effects seen at lower doses

Duration of Treatment

Following the American College of Physicians guidelines:

• Acute phase: 6-12 weeks
• Continuation phase: Continue treatment for 4-9 months after satisfactory response in patients with first episode of MDD 2
• Maintenance phase: For patients with 2 or more episodes, longer duration of therapy may be beneficial 2

Special Considerations

Medication Interactions

Dose adjustments may be necessary with:

• Strong CYP3A inducers (carbamazepine, phenytoin, rifampin): May require increased mirtazapine dose
• Strong CYP3A inhibitors (ketoconazole, clarithromycin): May require decreased mirtazapine dose
• Cimetidine: May require decreased mirtazapine dose 1

Discontinuation

• Gradual tapering: Always taper gradually rather than stopping abruptly to minimize discontinuation symptoms 1
• Monitoring: Assess for withdrawal symptoms during tapering

Monitoring and Follow-up

Following ACP recommendations:

• Initial follow-up: Begin within 1-2 weeks of treatment initiation 2
• Regular assessment: Monitor therapeutic response and adverse effects
• Treatment modification: If inadequate response occurs within 6-8 weeks, consider treatment modification 2

Common Side Effects to Monitor

• Most common: Somnolence (23%), dry mouth (25%), increased appetite (11%), and weight gain (10%) 4
• Advantage: Minimal sexual dysfunction compared to SSRIs 3
• Caution: Rare cases of agranulocytosis and neutropenia have been reported 4

Clinical Pearls

1. Mirtazapine is particularly useful for patients with depression accompanied by significant sleep disturbance, anxiety, or appetite/weight loss
2. The sedative effects are most pronounced at lower doses (15 mg) and may decrease at higher doses
3. Unlike SSRIs, mirtazapine has minimal sexual side effects and gastrointestinal disturbances
4. Always screen for bipolar disorder before initiating treatment 1
5. Allow sufficient time (1-2 weeks) between dose adjustments to properly evaluate response

By following this dosing regimen and monitoring protocol, clinicians can optimize the therapeutic benefits of mirtazapine while minimizing adverse effects in patients with major depressive disorder.