Savella (Milnacipran) Dosing for Fibromyalgia
The recommended dosing for Savella (milnacipran) is 100 mg/day or 200 mg/day given in divided doses (50 mg twice daily or 100 mg twice daily), with dose escalation starting at lower doses and titrating up over approximately 1 week to minimize side effects. 1
Standard Dosing Protocol
Target maintenance doses are 100-200 mg/day in divided doses (twice daily administration). 1, 2
Dose Escalation Schedule
Start with gradual titration over the first week to reach the target dose of 100-200 mg/day, as this approach was used successfully in clinical trials with 84% of patients reaching the highest dose (200 mg/day) without tolerability issues. 3
The typical starting dose in real-world practice averages 95 mg/day, though this varies, with approximately 17% of patients starting below recommended doses. 4
Most patients (80%) achieve and maintain USPI-recommended maintenance dosing during treatment, with 90% of treatment time spent at the maximum dose once reached. 4
Optimal Dosing Strategy
Both 100 mg/day and 200 mg/day doses demonstrate efficacy, with 37% of patients on 200 mg/day (100 mg twice daily) achieving at least 50% pain reduction compared to 14% on placebo. 3
Twice-daily dosing is superior to once-daily administration for fibromyalgia, as clinical trials specifically used divided doses and showed better outcomes with this regimen. 3, 5
The dose range of 50-200 mg in divided doses is effective, with 92% of twice-daily participants in trials achieving escalation to the target 200 mg dose. 5, 6
Clinical Efficacy Expectations
75% of milnacipran-treated patients report overall improvement compared to 38% with placebo, demonstrating robust efficacy beyond just pain reduction. 3
Milnacipran provides benefits for multiple fibromyalgia symptoms including pain, fatigue, depressed mood, sleep disturbances, and cognitive dysfunction, not just pain alone. 3, 7
Treatment duration averages 167 days in real-world practice, suggesting reasonable tolerability and sustained benefit. 4
Safety and Tolerability
Most adverse events are mild to moderate in intensity and transient in duration, with the drug being generally well tolerated at doses up to 200 mg/day. 3, 5
Dropout rates due to side effects are approximately double compared to placebo, though there is no difference in serious adverse events between milnacipran and placebo. 1
The number needed to harm (NNH) cannot be precisely calculated from available data, but the safety profile is considered acceptable given the efficacy benefits. 1
Special Considerations
Renal dose adjustment is required in patients with renal insufficiency, as milnacipran is excreted renally with a half-life of approximately 8 hours. 6
Caution is necessary in patients with heart disease, hypertension, epilepsy, glaucoma, bipolar disorder, and bleeding tendency, as with other SNRIs. 6
Efficacy is equal in patients with and without comorbid depression, though placebo response rates are higher in depressed patients, leading to greater overall efficacy in non-depressed fibromyalgia patients. 5
Integration into Treatment Algorithm
Milnacipran should be considered as part of a comprehensive approach that prioritizes non-pharmacological interventions (exercise, cognitive behavioral therapy) first, with pharmacological agents like milnacipran added when non-pharmacological approaches provide insufficient relief. 2
Milnacipran is particularly useful for patients who experience problematic sedation, dizziness, edema, or weight gain with pregabalin or gabapentin, offering an alternative mechanism of action. 7
Consider milnacipran specifically for fibromyalgia patients with prominent fatigue, cognitive dysfunction, or depressive symptoms, as it addresses these associated symptoms effectively. 7, 6