What is the typical dosing regimen for mirtazapine?

Mirtazapine Dosing

Start mirtazapine at 15 mg once daily at bedtime, and if inadequate response occurs, increase up to a maximum of 45 mg daily, with dose changes made no more frequently than every 1-2 weeks. 1

Initial Dosing

• Begin with 15 mg once daily, administered orally in the evening prior to sleep 1
• This starting dose is supported by FDA labeling and should be maintained for at least 1-2 weeks before considering dose adjustment 1
• The evening timing capitalizes on mirtazapine's sedating properties, which can improve sleep disturbances often present in depression 2, 3

Dose Titration

• If patients do not have adequate response to 15 mg, increase the dose up to a maximum of 45 mg per day 1
• Dose changes should not be made in intervals of less than 1-2 weeks to allow sufficient time for evaluation of response 1
• The American College of Physicians recommends assessing therapeutic response and adverse effects within 1-2 weeks of treatment initiation, with treatment modification strongly recommended if inadequate response occurs within 6-8 weeks 2

Dosing Adjustments for Drug Interactions

• With strong CYP3A inducers (carbamazepine, phenytoin, rifampin): Increase mirtazapine dose as needed; conversely, decrease dose if the inducer is discontinued 1
• With strong CYP3A4 inhibitors (ketoconazole, clarithromycin): Decrease mirtazapine dose; increase if the inhibitor is discontinued 1
• With cimetidine: Decrease mirtazapine dose during concomitant use; increase if cimetidine is discontinued 1

Special Populations

• Hepatic or renal impairment: Oral clearance decreases by approximately 30% with liver or moderate renal impairment, and by 50% with severe renal impairment 4
• Elderly and female patients: These populations show higher plasma concentrations and may require more cautious dosing 4

Duration of Treatment

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

Discontinuation

• Gradually reduce the dosage rather than stopping abruptly whenever possible to minimize withdrawal symptoms 1
• Screen patients for bipolar disorder, mania, or hypomania prior to initiating treatment 1
• At least 14 days must elapse between discontinuation of an MAOI and initiation of mirtazapine, and vice versa 1

Clinical Advantages Supporting This Dosing

• 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 2, 3
• The 20-40 hour elimination half-life supports once-daily dosing 3, 4
• It is particularly suitable for patients with depression accompanied by insomnia or weight loss due to its sleep-promoting and appetite-stimulating properties 2, 5