What is the recommended dose of Remeron (mirtazapine) for a patient with a history of depression and current stomach issues, particularly nausea?

Mirtazapine Dosing for Nausea

For nausea management in gastroparesis or functional dyspepsia, start mirtazapine at 7.5 mg at bedtime and titrate up to 30 mg at bedtime as needed for symptom control. 1

Dosing Algorithm for Nausea

Initial Dose:

• Start with 7.5 mg at bedtime 1
• This lower starting dose is specifically recommended in guidelines for managing gastrointestinal symptoms and is better tolerated than higher initial doses 1

Titration:

• If inadequate response after 1-2 weeks, increase to 15 mg at bedtime 2
• Maximum dose for nausea management: 30 mg at bedtime 1
• Do not make dose changes more frequently than every 1-2 weeks 2

Target Dose Range:

• The therapeutic range for nausea is 7.5-30 mg/day 1
• This is lower than the typical antidepressant dosing range of 15-45 mg/day 2

Mechanism and Benefits for Nausea

Mirtazapine's anti-nausea effects are mediated through multiple mechanisms that are distinct from its antidepressant properties 3, 4:

• 5-HT3 receptor antagonism provides direct antiemetic effects 3, 5
• Histamine H1 receptor antagonism contributes to sedation and appetite stimulation 3, 5
• Alpha-2 adrenergic receptor blockade enhances noradrenergic neurotransmission 5

Clinical Evidence in Gastroparesis

The 2022 AGA Clinical Practice Update on medically refractory gastroparesis specifically lists mirtazapine as a treatment option for nausea at doses of 7.5-30 mg/day 1. A cohort study of 30 gastroparesis patients demonstrated that mirtazapine improved refractory nausea and vomiting 1. Additionally, mirtazapine improved weight loss and early satiation in functional dyspepsia patients 1.

Important Clinical Considerations

Timing of Administration:

• Always administer at bedtime to leverage sedative effects and minimize daytime somnolence 1
• The sedative effect is paradoxically more pronounced at lower doses (7.5 mg) than at higher therapeutic doses 6

Beneficial Side Effects for This Indication:

• Promotes appetite and weight gain - advantageous in gastroparesis patients with poor oral intake 1
• Improves sleep - helpful for patients with chronic nausea affecting sleep quality 1
• Sedation - can be therapeutic rather than problematic when dosed at bedtime 6

Onset of Action:

• Antiemetic effects may be observed within 1-2 weeks of starting therapy 1, 4
• This is faster than the typical 2-4 week onset for antidepressant effects 4, 6

Common Pitfalls to Avoid

Do not start at 15 mg for nausea management - The FDA-approved starting dose of 15 mg for depression 2 is higher than needed for nausea control, and starting at 7.5 mg improves tolerability while maintaining efficacy for gastrointestinal symptoms 1.

Do not exceed 30 mg/day for nausea - Higher doses (up to 45 mg) are used for depression 2, but the gastroparesis guidelines specifically cap the dose at 30 mg/day for gastrointestinal symptom management 1.

Monitor for excessive sedation - While sedation at bedtime is desirable, excessive daytime somnolence may occur, particularly at the 7.5 mg dose 6. If this occurs, consider increasing to 15 mg, as sedation paradoxically decreases at higher doses 6.

Drug Interactions Requiring Dose Adjustment

Reduce mirtazapine dose with:

• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin) 2
• Cimetidine 2

Increase mirtazapine dose with:

• Strong CYP3A inducers (carbamazepine, phenytoin, rifampin) 2

Special Populations

Elderly patients and those with hepatic/renal impairment:

• Start at 7.5 mg and titrate more cautiously 1
• Mirtazapine clearance may be reduced in these populations 6

Patients with depression and nausea:

• Mirtazapine addresses both conditions simultaneously 1, 4
• May titrate up to 45 mg/day if treating both depression and nausea, though nausea control typically achieved at lower doses 2