Fetzima (Levomilnacipran) Treatment Protocol for Major Depressive Disorder
Levomilnacipran (Fetzima) is an effective second-generation antidepressant for adults with major depressive disorder (MDD), with FDA-approved dosing ranging from 40-120 mg once daily, demonstrating significant superiority over placebo in improving both depressive symptoms and functional outcomes. 1
Dosing and Administration
Initial Dosing:
- Start with 20 mg once daily for 2 days
- Increase to 40 mg once daily on day 3
- Maximum recommended dose: 120 mg once daily
Dose Titration:
- Based on efficacy and tolerability
- Can be increased in increments of 40 mg at intervals of at least 2 days
- Doses of 40 mg, 80 mg, and 120 mg have all demonstrated statistically significant superiority over placebo 1
Administration:
- Take once daily with or without food
- Swallow capsules whole; do not open, chew, or crush
Efficacy Profile
Levomilnacipran has demonstrated efficacy in multiple clinical trials:
- Significant improvements in Montgomery-Asberg Depression Rating Scale (MADRS) scores compared to placebo across all studied doses (40 mg, 80 mg, and 120 mg) 1
- Particularly effective at improving measures of motivation, energy, and interest 2
- Shows significant improvement in functional outcomes as measured by the Sheehan Disability Scale (SDS) 1, 3
- In flexible-dose studies, approximately 44% of patients ended up on the 120 mg dose, with 34% on 80 mg and 21% on 40 mg 1
Treatment Duration
Following the American College of Physicians guidelines for MDD treatment phases 4, 5:
Acute Phase (6-12 weeks):
- Monitor response beginning 1-2 weeks after treatment initiation
- Assess for improvement in depressive symptoms using standardized scales (e.g., MADRS)
Continuation Phase (4-9 months after achieving remission):
- Continue treatment to prevent relapse
- Monthly monitoring for ongoing symptoms, side effects, and adherence
Maintenance Phase (≥1 year or longer):
- For recurrent MDD (2+ episodes), consider longer treatment duration
- Risk of recurrence increases with each episode: 50% after first episode, 70% after second, and 90% after third episode 5
Monitoring and Assessment
- Begin assessing response 1-2 weeks after treatment initiation
- Monitor monthly during continuation phase
- Assess for:
- Ongoing depressive symptoms
- Suicide risk
- Adverse effects
- Treatment adherence
- Environmental stressors 5
Common Side Effects
Most common adverse events (≥5% and at least twice the rate of placebo) include:
- Nausea
- Dry mouth
- Increased heart rate
- Constipation
- Dizziness
- Hyperhidrosis (excessive sweating)
- Urinary hesitation
- Erectile dysfunction 1, 3
Special Considerations
- Cardiovascular Monitoring: Regular monitoring of blood pressure and heart rate is recommended due to potential for tachycardia and hypertension 6
- Discontinuation: When stopping treatment, gradual dose reduction is recommended to minimize discontinuation symptoms
- Pharmacokinetics: Primarily excreted unchanged in urine (58%), with minimal hepatic metabolism 1
- Drug Interactions: Use caution with MAOIs (contraindicated), other serotonergic drugs, and drugs affecting norepinephrine
Unique Properties of Levomilnacipran
- Unlike other SNRIs, levomilnacipran has greater potency for norepinephrine reuptake inhibition compared to serotonin reuptake 2, 6, 7
- This unique pharmacological profile may be particularly beneficial for patients with prominent symptoms of fatigue and lack of motivation 2
- Generally well tolerated with minimal propensity for metabolic disturbance or weight gain 2
Limitations and Considerations
- No head-to-head trials comparing levomilnacipran to other antidepressants are available 2, 8, 6
- Long-term efficacy data for relapse prevention is more limited compared to acute treatment data 6
- Cardiovascular safety requires further investigation, especially for long-term treatment 6
Levomilnacipran represents a valuable option in the antidepressant armamentarium, particularly for patients who may benefit from its greater noradrenergic activity.