What is the appropriate dose increase for mirtazapine (Remeron) in a patient with inadequate response to the current dose?

Mirtazapine Dose Escalation for Inadequate Response

If a patient has inadequate response to the initial 15 mg dose of mirtazapine, increase the dose up to a maximum of 45 mg per day, with dose changes made in intervals of at least 1 to 2 weeks to allow sufficient time for evaluation of response. 1

Standard Dosing Algorithm

Starting dose:

• Begin with 15 mg once daily, administered orally in the evening prior to sleep 1

Dose escalation for inadequate response:

• If no adequate response at 15 mg, increase to 30 mg daily 1, 2
• If still inadequate at 30 mg, may increase to maximum of 45 mg daily 1, 3
• Critical timing: Wait at least 1-2 weeks between dose adjustments to properly evaluate response at each dose level 1

Rationale for Dose Increases

The pharmacodynamic properties of mirtazapine support dose escalation for inadequate response 3, 4. The drug enhances both noradrenergic and serotonergic neurotransmission through α2-adrenergic receptor blockade, with specific serotonergic effects mediated via 5-HT1 receptors while blocking 5-HT2 and 5-HT3 receptors 4, 2. Higher doses (30-45 mg) may provide greater therapeutic benefit in patients who do not respond adequately to 15 mg 3, 5.

Important Dosing Considerations

Paradoxical sedation pattern:

• Sedation is actually more common at lower doses (15 mg) due to antihistaminic (H1) activity 3, 6
• Sedation becomes less frequent at higher dosages (30-45 mg), making dose escalation appropriate even if initial sedation occurs 3

Time to response:

• Clinical antidepressant effect typically occurs in 2-4 weeks, though sleep and anxiety symptoms may improve within the first week 4, 6
• Early improvement (within 1 week) in rating scales has been documented in some studies 6

Dose Modifications for Drug Interactions

Decrease mirtazapine dose when combined with:

• Strong CYP3A4 inhibitors (ketoconazole, clarithromycin) 1
• Cimetidine 1

Increase mirtazapine dose when combined with:

• Strong CYP3A inducers (carbamazepine, phenytoin, rifampin) 1

Common Pitfalls to Avoid

• Do not increase doses more frequently than every 1-2 weeks - insufficient time to evaluate response leads to inappropriate dose escalation 1
• Do not stop at 15 mg if response is inadequate - the effective dosage range is 15-45 mg, and many patients require higher doses 1, 3
• Do not avoid dose increases due to initial sedation - sedation typically decreases at higher therapeutic doses 3, 6
• Do not abruptly discontinue - gradually reduce dosage to minimize withdrawal symptoms 1