What are the guidelines for mirtazapine (Remeron) dosing increments?

Mirtazapine Dosing Increments

Start mirtazapine at 15 mg once daily at bedtime, and if inadequate response after 6-8 weeks, increase to 30 mg daily; further titration to the maximum dose of 45 mg daily may be done if needed, with dose changes made no more frequently than every 1-2 weeks. 1

Initial Dosing Strategy

• Begin with 15 mg once daily, preferably in the evening prior to sleep 1
• This starting dose may produce therapeutic effects in some patients, with expected steady-state plasma concentrations of 7.3 ± 3.2 ng/mL 2
• The 15 mg dose is appropriate for most patients and helps minimize initial sedation 2

Titration Schedule

The key principle is patience: dose changes must not be made in intervals of less than 1-2 weeks to allow sufficient time for evaluation of response to a given dose 1

• If no adequate response after 6-8 weeks at 15 mg, increase to 30 mg daily (expected plasma concentration: 18 ± 7 ng/mL) 2, 1
• If response remains inadequate at 30 mg, increase to the maximum approved dose of 45 mg daily (expected plasma concentration: 28 ± 12 ng/mL) 2, 1
• The therapeutic range is established as 15-45 mg/day, with recommended plasma concentrations of 40-80 ng/mL 2

Monitoring Timeline

• Begin assessing therapeutic response and adverse effects within 1-2 weeks of treatment initiation 3
• If the patient does not have an adequate response within 6-8 weeks at a given dose, treatment modification is strongly recommended 3
• Some patients may experience improvements in sleep disturbances and anxiety symptoms within the first week, though full antidepressant effect typically requires 2-4 weeks 4

Common Pitfalls to Avoid

Do not increase doses too rapidly - the 1-2 week minimum interval between dose changes is critical because mirtazapine reaches steady state in 4-6 days, and you need additional time to assess clinical response 1, 5

• Avoid the temptation to escalate doses quickly in non-responders; premature dose increases before adequate trial duration may lead to unnecessary side effects without therapeutic benefit 1
• The sedation often seen at lower doses (particularly 15 mg) may paradoxically improve at higher therapeutic doses (30-45 mg), so don't abandon the medication prematurely due to initial sedation 6

Special Populations

• Elderly patients: Consider starting at approximately 50% of the standard adult dose due to higher risk of adverse reactions and higher plasma concentrations in this population 2, 5
• Renal or hepatic impairment: Dose reduction should be considered, as moderate impairment causes approximately 30% decrease in clearance, and severe renal impairment causes 50% decrease 2, 5

Drug Interaction Considerations

Dose adjustments may be necessary based on concomitant medications:

• Strong CYP3A inducers (carbamazepine, phenytoin, rifampin): May need to increase mirtazapine dose - for example, carbamazepine causes a 60% decrease in mirtazapine plasma concentrations 1, 5
• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin): May need to decrease mirtazapine dose to avoid excessive plasma levels 1
• Cimetidine: May require dose reduction of mirtazapine due to increased plasma concentrations 1

Off-Label Higher Dosing

While the FDA-approved maximum is 45 mg daily, some clinicians use doses above 45 mg (up to 60 mg) in treatment-resistant cases, though this is off-label 2. Expected plasma concentration at 60 mg/day is 38 ± 16 ng/mL 2. This should only be considered after adequate trials at standard doses and preferably with specialist consultation.

Discontinuation

Gradually taper the dose rather than stopping abruptly whenever possible to minimize discontinuation symptoms 1