What is the approach to mirtazapine (Remeron) dose optimization in a patient already taking 10 mg at night?

Mirtazapine Dose Optimization from 10 mg

For a patient already on 10 mg mirtazapine at night, increase to 15 mg once daily at bedtime for at least 1-2 weeks, then titrate to 30 mg if response is inadequate after 6-8 weeks, with a maximum dose of 45 mg daily. 1

Current Dose Assessment

Your patient is on a subtherapeutic dose. The 10 mg dose is below the FDA-approved starting dose and may paradoxically cause more sedation than therapeutic benefit:

• The FDA-approved starting dose is 15 mg once daily, preferably in the evening prior to sleep 1
• Doses below 15 mg (such as 7.5-10 mg) are associated with increased sedation and are typically reserved only for patients with documented extreme sensitivity to psychotropic medications 2
• The 10 mg dose delays onset of antidepressant action and essentially adds 2 weeks to the expected time to therapeutic benefit 2

Recommended Titration Algorithm

Step 1: Immediate adjustment

• Increase to 15 mg once daily at bedtime now 1, 3
• This is the minimum therapeutic starting dose with expected steady-state plasma concentrations of 7.3 ± 3.2 ng/mL 3
• Assess for therapeutic response within 1-2 weeks 2

Step 2: Evaluate response at 6-8 weeks

• If inadequate response after 6-8 weeks at 15 mg, increase to 30 mg once daily 1, 3
• Expected steady-state plasma concentrations at 30 mg: 18 ± 7 ng/mL 3
• The therapeutic range is 15-45 mg/day with recommended plasma concentrations of 40-80 ng/mL 3

Step 3: Further optimization if needed

• If response remains inadequate, increase to 45 mg once daily (maximum FDA-approved dose) 1, 3
• Expected steady-state plasma concentrations at 45 mg: 28 ± 12 ng/mL 3
• Dose changes should not be made in intervals less than 1-2 weeks to allow sufficient time for evaluation of response 1

Critical Timing Considerations

The current 10 mg dose is problematic because:

• Starting at subtherapeutic doses (7.5-10 mg) for 2 weeks delays the onset of antidepressant action 2
• Adequate response evaluation requires 6-8 weeks at therapeutic doses (≥15 mg) 2
• The patient has essentially been undertreated, which may explain any lack of efficacy

Common Pitfalls to Avoid

Sedation paradox: Increased sedation is actually related to subtherapeutic dosages, and is reported in substantially fewer patients when the drug is used in appropriate dosages (≥15 mg as a single evening dose) from the beginning of treatment 4. Moving from 10 mg to 15 mg may actually reduce sedation while improving efficacy.

Premature dose escalation: Do not increase beyond 15 mg before allowing 6-8 weeks for adequate response evaluation 2, 1

Abrupt discontinuation: If stopping mirtazapine, gradually reduce the dosage rather than stopping abruptly to avoid discontinuation adverse reactions 1

Special Populations Requiring Dose Modification

• Elderly patients: Consider approximately 50% of the initial adult dose due to higher risk of adverse reactions 3
• Hepatic or renal impairment: Dose reduction should be considered 3
• Drug interactions: Decrease dose with strong CYP3A4 inhibitors (ketoconazole, clarithromycin) or cimetidine; increase dose with strong CYP3A inducers (carbamazepine, phenytoin, rifampin) 1

Expected Adverse Effects at Therapeutic Doses

At therapeutic doses (≥15 mg), common side effects include somnolence, increased appetite, weight gain, and dry mouth 3. These are generally dose-dependent and may improve as the patient adjusts to the medication 4, 5. The drug has minimal cardiovascular and anticholinergic effects, and essentially lacks serotonergic effects such as gastrointestinal symptoms, insomnia, and sexual dysfunction 5.