What is the recommended dosage and treatment protocol for Fetzima (levomilnacipran) in adults with major depressive disorder?

Fetzima (Levomilnacipran) Dosage and Treatment Protocol for Major Depressive Disorder

The recommended dosage protocol for Fetzima (levomilnacipran) in adults with MDD is to initiate at 20 mg once daily for 2 days, then increase to 40 mg once daily, with potential incremental increases of 40 mg at intervals of 2 or more days based on clinical response and tolerability, up to a maximum recommended dosage of 120 mg once daily. 1

Initial Dosing and Titration

• Starting dose: 20 mg once daily for 2 days
• Initial target dose: 40 mg once daily
• Dose adjustments: May increase in increments of 40 mg at intervals of ≥2 days
• Therapeutic range: 40-120 mg once daily
• Maximum dose: 120 mg once daily
• Administration: Take at approximately the same time each day, with or without food
• Capsule administration: Swallow whole; do not open, chew, or crush 1

Dosage Adjustments for Special Populations

Renal Impairment

• End-stage renal disease: Not recommended
• Severe impairment (CrCl 15-29 mL/min): Maximum 40 mg once daily
• Moderate impairment (CrCl 30-59 mL/min): Maximum 80 mg once daily
• Mild impairment (CrCl 60-89 mL/min): No dosage adjustment needed 1, 2

Concomitant Medications

• Strong CYP3A4 inhibitors: Maximum dose should not exceed 80 mg once daily 1

Treatment Duration and Phases

The treatment of MDD follows three distinct phases:

1. Acute Phase: 6-12 weeks
2. Continuation Phase: 4-9 months
3. Maintenance Phase: ≥1 year 3, 4

For optimal outcomes:

• First episode: Continue treatment for 4-9 months after achieving remission
• Recurrent MDD (2+ episodes): Years to lifelong treatment may be beneficial 4
• Risk of recurrence increases with each episode: 50% after first, 70% after second, 90% after third episode 4

Monitoring Protocol

• Initial assessment: Screen for bipolar disorder before starting treatment 1
• Early monitoring: Begin assessment of response 1-2 weeks after treatment initiation
• Regular monitoring: Assess for treatment response, side effects, and suicidal thoughts/behaviors
• Post-remission: Monitor monthly for 6-12 months 4

Discontinuation Protocol

• Gradual tapering: Recommended instead of abrupt discontinuation
• If symptoms occur: Consider resuming previously prescribed dose and decreasing more gradually
• Post-discontinuation monitoring: Close follow-up for at least 2-3 months due to high relapse risk 4, 1

Important Safety Considerations

• Boxed warning: Increased risk of suicidal thoughts and behaviors, especially in young adults 1
• Common side effects: Headache (22%), nausea (16%) 5
• Cardiovascular effects: Mean increases in pulse rate (9.1 bpm) and blood pressure (3.9/3.3 mmHg) have been observed 5
• MAOI interaction: Allow at least 14 days between discontinuing an MAOI and starting levomilnacipran; allow at least 7 days after stopping levomilnacipran before starting an MAOI 1

Clinical Efficacy

Levomilnacipran ER has demonstrated significantly greater improvements in depressive symptoms compared to placebo in 8-week clinical trials, with maintained efficacy during longer-term treatment 6, 5. It has a higher potency for norepinephrine reuptake inhibition compared to other SNRIs, which may represent a unique therapeutic characteristic 7.

Therapeutic plasma concentrations of levomilnacipran at approved doses (40-120 mg) exceed the concentrations that inhibit reuptake of norepinephrine by >90% and serotonin by >80% in vitro 8, supporting its clinical efficacy in MDD.