What is the recommended dosing schedule for mirtazapine (Remeron) when taken in the evening for major depressive disorder?

Mirtazapine Evening Dosing for Major Depressive Disorder

Mirtazapine should be administered at a dose of 15 mg once daily in the evening prior to sleep, with titration up to 30 mg at bedtime as needed for optimal antidepressant effect. 1

Dosing Recommendations

Initial Dosing

• Start with 15 mg once daily in the evening prior to sleep 1
• Lower doses (7.5-15 mg) tend to be more sedating due to predominant H1 receptor antagonism 2
• The sedative effect can be beneficial for patients with depression and insomnia 3

Titration

• If inadequate response to initial dose, increase after 1-2 weeks 1
• Titrate to 30 mg at bedtime for optimal antidepressant effect 3, 2
• Maximum recommended dose is 45 mg daily 1

Pharmacological Effects by Dose

• At lower doses (7.5-15 mg): More pronounced sedation due to stronger H1 receptor antagonism 2
• At higher doses (30-45 mg): Better antidepressant effect with relatively less sedation 2, 4

Clinical Considerations

Benefits of Evening Administration

• Leverages the sedative properties to improve sleep disturbances associated with depression 3
• Once-daily dosing is supported by mirtazapine's 20-40 hour half-life 4, 5
• Evening dosing minimizes daytime impairment from sedation 2

Side Effect Profile

• Most common side effects:
  • Somnolence (54%) 2
  • Increased appetite (17%) 2
  • Weight gain (10%) 2
  • Dry mouth (25%) 2

Special Populations

• Elderly patients may require lower starting doses (7.5-15 mg) due to reduced clearance 2
• Patients with hepatic or renal impairment may require dose adjustments 1, 4

Monitoring and Follow-up

• Assess therapeutic response after 4-8 weeks of treatment 3
• Monitor for common side effects, particularly sedation, increased appetite, and weight gain 2
• Treatment should continue for 4-9 months after satisfactory response for first episode of depression 2

Drug Interactions

• Strong CYP3A inducers may require mirtazapine dose increase 1
• Strong CYP3A inhibitors may require mirtazapine dose decrease 1
• Avoid MAOIs due to risk of serotonin syndrome (allow 14 days between stopping one and starting the other) 1

Clinical Pearls

• Increased sedation is often related to subtherapeutic dosages and is reported less frequently when appropriate dosages (≥15 mg as a single evening dose) are used from the beginning of treatment 4
• The antidepressant effect may begin as early as 1 week after starting treatment 4
• Mirtazapine has minimal cardiovascular and anticholinergic effects compared to tricyclic antidepressants 5
• Unlike SSRIs, mirtazapine has minimal sexual dysfunction side effects 4

By following these dosing recommendations, clinicians can optimize the therapeutic benefits of mirtazapine while minimizing potential side effects for patients with major depressive disorder.