What is the starting dose of Remeron (mirtazapine) for an adult patient with no significant medical history and what potential interactions should be considered?

Starting Dose and Drug Interactions for Mirtazapine (Remeron)

The recommended starting dose of mirtazapine is 15 mg once daily, administered orally in the evening prior to sleep, with dose increases up to a maximum of 45 mg per day if needed, and dose changes should not be made more frequently than every 1-2 weeks. 1

Standard Dosing Protocol

• Initial dose: 15 mg once daily at bedtime 1
• Dose titration: Increase as needed up to 45 mg/day maximum 1
• Timing of dose adjustments: Wait at least 1-2 weeks between dose changes to allow adequate time for response evaluation 1
• Administration timing: Preferably in the evening prior to sleep 1

The FDA-approved dosing differs from some older guidelines that suggested starting at 7.5 mg 2, but the current FDA label clearly establishes 15 mg as the recommended starting dose 1.

Clinical Onset and Pharmacokinetics

• Onset of antidepressant effect: 2-4 weeks for full response, though sleep disturbances and anxiety may improve within the first week 3
• Peak plasma concentration: Reached within 2 hours after oral administration 4
• Elimination half-life: 20-40 hours, enabling once-daily dosing 3, 5
• Time to steady state: 4-6 days 4
• Bioavailability: Approximately 50% due to first-pass metabolism 4

Critical Drug Interactions Requiring Dose Adjustments

Strong CYP3A4 Inducers

• Carbamazepine, phenytoin, rifampin: Increase mirtazapine dose when coadministered; decrease mirtazapine dose if the inducer is discontinued 1
• Carbamazepine specifically causes a 60% decrease in mirtazapine plasma concentrations 4

Strong CYP3A4 Inhibitors

• Ketoconazole, clarithromycin: Decrease mirtazapine dose when coadministered; increase mirtazapine dose if the inhibitor is discontinued 1

Cimetidine

• Decrease mirtazapine dose when coadministered with cimetidine; increase mirtazapine dose if cimetidine is discontinued 1

MAOI Antidepressants - Absolute Contraindication

• At least 14 days must elapse between discontinuation of an MAOI and initiation of mirtazapine 1
• At least 14 days must elapse after stopping mirtazapine before starting an MAOI 1

Clinically Significant but Non-Dose-Adjusting Interactions

SSRIs (Paroxetine, Fluoxetine)

• Paroxetine increases mirtazapine plasma concentrations by 17% 4
• Fluoxetine increases mirtazapine plasma concentrations by 32% 4
• These increases are modest and do not typically require dose adjustment, but monitor for increased sedation and other side effects 4

Low Interaction Potential with Other Drugs

• Mirtazapine has little inhibitory effect on CYP isoenzymes, so it minimally affects the pharmacokinetics of coadministered drugs 4
• In vitro studies show mirtazapine is not a potent inhibitor or inducer of CYP1A2, CYP2D6, or CYP3A4 6

Special Population Considerations

Hepatic Impairment

• Liver impairment causes approximately 30% decrease in oral mirtazapine clearance; consider lower starting dose or less frequent dosing 4

Renal Impairment

• Moderate renal impairment causes approximately 30% decrease in clearance 4
• Severe renal impairment causes 50% decrease in clearance; dose reduction warranted 4

Elderly Patients

• Elderly patients show higher plasma concentrations than young adults; consider starting at lower end of dosing range 4

Gender Differences

• Females show higher plasma concentrations than males; monitor for increased side effects 4

Screening Requirements Before Initiation

• Screen for personal or family history of bipolar disorder, mania, or hypomania prior to starting mirtazapine 1
• This screening is critical to avoid precipitating manic episodes in patients with undiagnosed bipolar disorder 1

Discontinuation Protocol

• Gradually reduce the dosage rather than stopping abruptly whenever possible to minimize withdrawal symptoms 1
• Adverse reactions may occur upon discontinuation or dose reduction 1

Common Pitfalls to Avoid

• Do not increase dose more frequently than every 1-2 weeks - insufficient time to assess response leads to unnecessary dose escalation 1
• Do not combine with MAOIs or start too soon after MAOI discontinuation - risk of serotonin syndrome 1
• Do not overlook the need for dose adjustment with strong CYP3A4 inducers like carbamazepine - can result in therapeutic failure due to 60% reduction in drug levels 4
• Do not assume sedation will worsen with higher doses - sedation is actually more common at lower doses due to antihistaminic effects and may decrease at therapeutic doses ≥15 mg 5