What is the typical dosing regimen for Mirtazapine (Remeron)?

Mirtazapine Dosing for Major Depressive Disorder

Start mirtazapine at 15 mg once daily at bedtime, and if inadequate response after 6-8 weeks, increase to 30 mg daily, with a maximum dose of 45 mg daily. 1

Initial Dosing

• Begin with 15 mg once daily, administered orally 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 therapeutic range is established as 15-45 mg/day, with recommended plasma concentrations of 40-80 ng/mL 2

Dose Titration Strategy

• If no adequate response after 6-8 weeks at 15 mg, increase to 30 mg daily 2, 1
• Expected steady-state plasma concentrations at 30 mg are 18 ± 7 ng/mL 2
• Do not make dose changes in intervals less than 1-2 weeks to allow sufficient time for evaluation of response 1
• The maximum approved dose is 45 mg per day, with expected plasma concentrations of 28 ± 12 ng/mL 2, 1

Clinical Response Timeline

• Begin assessing therapeutic response and adverse effects within 1-2 weeks of treatment initiation 3
• Mirtazapine has a faster onset of action than some SSRIs (fluoxetine, paroxetine, sertraline), with sleep disturbances and anxiety symptoms potentially improving in the first week 3, 4
• If inadequate response within 6-8 weeks, treatment modification is strongly recommended 3

Duration of Treatment

• Continue treatment for 4-9 months after satisfactory response in first-episode major depressive disorder 3
• For patients with 2 or more depressive episodes, even longer duration of therapy may be beneficial 3

Special Populations

Elderly Patients

• Consider a lower initial dose (approximately 50% of the standard adult dose) due to higher risk of adverse reactions 2

Renal or Hepatic Impairment

• A dose reduction should be considered in patients with renal or hepatic impairment 2

Drug Interactions Requiring Dose Adjustment

Strong CYP3A Inducers (carbamazepine, phenytoin, rifampin)

• Increase mirtazapine dose when starting a strong CYP3A inducer 1
• Conversely, decrease dose if the inducer is discontinued 1

Strong CYP3A4 Inhibitors (ketoconazole, clarithromycin)

• Decrease mirtazapine dose when starting a strong CYP3A4 inhibitor 1
• Conversely, increase dose if the inhibitor is discontinued 1

Cimetidine

• Decrease mirtazapine dose with concomitant cimetidine use 1
• Increase dose if cimetidine is discontinued 1

Clinical Advantages

• Particularly suitable for patients with depression accompanied by insomnia or weight loss, as it promotes sleep, appetite, and weight gain 3, 5
• Effective for anxiety symptoms associated with depression, potentially reducing need for concomitant anxiolytic medications 3
• Has minimal cardiovascular and anticholinergic effects, and lacks serotonergic effects such as gastrointestinal symptoms and sexual dysfunction 4

Common Side Effects to Monitor

• Somnolence/sedation, increased appetite and weight gain, dry mouth, sleep disorders, and constipation or diarrhea 3, 4
• The elimination half-life of 20-40 hours enables once-daily bedtime dosing 4

Discontinuation

• Gradually reduce the dosage rather than stopping abruptly whenever possible to avoid withdrawal reactions 1

Important Screening

• Screen patients for personal or family history of bipolar disorder, mania, or hypomania prior to initiating treatment 1
• At least 14 days must elapse between discontinuation of an MAOI antidepressant and initiation of mirtazapine, and vice versa 1

Off-Label Higher Dosing

• Some clinicians use doses above 45 mg daily to attain optimal efficacy in treatment-resistant cases, though this exceeds FDA-approved dosing 2