What is the recommended dosing for mirtazapine (Remeron)?

Mirtazapine Dosing

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, preferably in the evening prior to sleep. 1
• This starting dose of 15 mg may produce therapeutic effects in some patients, with expected steady-state plasma concentrations of 7.3 ± 3.2 ng/mL. 2
• The elimination half-life of 20-40 hours enables convenient once-daily bedtime dosing. 3

Dose Titration

• If patients do not have adequate response to the initial 15 mg dose after 6-8 weeks, increase to 30 mg daily. 2, 1
• Expected steady-state plasma concentrations at 30 mg daily are 18 ± 7 ng/mL. 2
• Dose changes should not be made in intervals of less than 1 to 2 weeks to allow sufficient time for evaluation of response to a given dose. 1
• The maximum approved dose is 45 mg per day, with expected steady-state plasma concentrations of 28 ± 12 ng/mL. 2, 1

Clinical Response Timeline

• Begin assessing patient status, therapeutic response, and adverse effects within 1-2 weeks of treatment initiation. 4
• Mirtazapine has a faster onset of action than some SSRIs such as fluoxetine, paroxetine, and sertraline, with sleep disturbances and anxiety symptoms potentially improving in the first week of treatment. 4, 3
• If the patient does not have an adequate response within 6-8 weeks, treatment modification is strongly recommended. 4

Special Populations

• In elderly patients, consider a lower initial dose (approximately 50% of the initial dose in adults) due to higher risk of adverse reactions. 2
• In patients with renal or hepatic impairment, a dose reduction should be considered. 2

Drug Interactions Requiring Dose Adjustment

• With strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin): An increase in mirtazapine dosage may be needed; conversely, decrease the dose if the inducer is discontinued. 1
• With strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): A decrease in mirtazapine dosage may be needed; conversely, increase the dose if the inhibitor is discontinued. 1
• With cimetidine: A decrease in mirtazapine dosage may be needed; conversely, increase the dose if cimetidine is discontinued. 1

Duration of Treatment

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

Discontinuation

• Gradually reduce the dosage of mirtazapine rather than stopping abruptly whenever possible to minimize adverse reactions upon discontinuation. 1

Common Side Effects to Monitor

• Common side effects include somnolence/sedation, increased appetite and weight gain, dry mouth, sleep disorders, and constipation or diarrhea. 4, 3
• Sedation is more common at lower doses and may decrease at therapeutic doses ≥15 mg. 5

Clinical Advantages

• Mirtazapine is particularly suitable for patients with depression accompanied by insomnia or weight loss, as it promotes sleep, appetite, and weight gain. 4, 6
• It has minimal cardiovascular and anticholinergic effects, and essentially lacks serotonergic effects such as gastrointestinal symptoms and sexual dysfunction. 3