What is the recommended dosing for mirtazapine (Remeron)?

Mirtazapine Dosing Recommendations

The recommended dosing for mirtazapine (Remeron) is to start at 15 mg once daily at bedtime, with dose increases up to a maximum of 45 mg daily based on clinical response and tolerability. 1

Initial Dosing and Titration

• Starting dose: 15 mg once daily, administered orally in the evening before sleep 1
• Titration: Increase dose in 7.5-15 mg increments at intervals of 1-2 weeks to allow sufficient time for evaluation of response 1
• Maximum dose: 45 mg daily 1
• Sedative effects: Most pronounced at lower doses (7.5-15 mg); sedation may actually decrease at higher doses 2

Dosing by Indication

Depression

• Standard dosing applies (15-45 mg daily)
• Therapeutic effects typically begin in 2-4 weeks, though sleep and anxiety symptoms may improve within the first week 2

Insomnia

• Lower doses (7.5-15 mg) are more sedating and effective for promoting sleep 3, 4
• The American Family Physician notes that mirtazapine is "potent and well tolerated; promotes sleep, appetite, and weight gain" 3

Disorders of Gut-Brain Interaction

• Starting dose of 15 mg once daily
• May be titrated up to 45 mg once daily based on response 3
• Particularly useful for patients with gastrointestinal symptoms and sleep disturbances

Special Populations

Elderly Patients

• Consider starting at a lower dose (7.5 mg)
• Titrate more slowly due to potential for increased side effects
• Elderly patients may have reduced clearance of mirtazapine 5

Hepatic or Renal Impairment

• Careful dosage titration is recommended
• Regular monitoring for adverse events is necessary
• Liver impairment causes approximately 30% decrease in oral clearance
• Severe renal impairment causes about 50% decrease in clearance 5

Pharmacokinetic Considerations

• Bioavailability: Approximately 50% due to first-pass metabolism 5
• Half-life: 20-40 hours, allowing for once-daily dosing 2, 5
• Steady state: Reached within 4-6 days of consistent dosing 5
• Gender differences: Females typically show higher plasma concentrations than males 5

Drug Interactions

• CYP3A4 inducers (carbamazepine, phenytoin, rifampin): May require increased mirtazapine dose 1
• CYP3A4 inhibitors (ketoconazole, clarithromycin): May require decreased mirtazapine dose 1
• Cimetidine: May require decreased mirtazapine dose 1
• MAOIs: Allow at least 14 days between stopping an MAOI and starting mirtazapine, and vice versa 1

Common Side Effects and Management

• Sedation: Most common at lower doses (7.5-15 mg); may improve with continued use or by administering at bedtime 2, 6
• Increased appetite/weight gain: Monitor weight regularly, especially during initial treatment 2, 6
• Dry mouth: Usually mild; ensure adequate hydration 6
• Dizziness: Usually transient; monitor for fall risk, especially in elderly 6

Discontinuation

• Gradual taper: Reduce dose gradually rather than stopping abruptly to minimize withdrawal symptoms 1
• Monitoring: Watch for discontinuation symptoms such as dizziness, sensory disturbances, anxiety, and sleep disturbances 1

Clinical Pearls

• Mirtazapine has a unique mechanism of action as a noradrenergic and specific serotonergic antidepressant (NaSSA) 2, 7
• Unlike many other antidepressants, mirtazapine has minimal sexual dysfunction side effects 2, 7
• The sedating effects are most pronounced at lower doses due to higher affinity for H1 histamine receptors, which become saturated at lower doses 2
• Mirtazapine has minimal cardiovascular and anticholinergic effects compared to tricyclic antidepressants 2
• Mirtazapine appears safe in overdose with primarily sedation as the main effect 2

Remember that while mirtazapine is generally well-tolerated, rare cases of agranulocytosis and neutropenia have been reported, so monitoring for unusual infections, fever, or sore throat is recommended, particularly early in treatment 7.