General Information

Savella (milnacipran) is a selective serotonin and norepinephrine reuptake inhibitor. It affects the two neurotransmitters almost equally (a 3-to-1 norepinephrine to serotonin balance). However, the exact mechanism of the central pain inhibitory action of milnacipran and its ability to improve the symptoms of fibromyalgia in humans are unknown.

Savella is specifically indicated for the management of fibromyalgia in adults.

Mechanism of Action

Savella (milnacipran) is a selective serotonin and norepinephrine reuptake inhibitor. It affects the two neurotransmitters almost equally (a 3:1 norepinephrine to serotonin balance). However, the exact mechanism of the central pain inhibitory action of milnacipran and its ability to improve the symptoms of fibromyalgia in humans are unknown.

Side Effects

Adverse events associated with the use of Savella may include, but are not limited to, the following:

• nausea
• headache
• constipation
• hot flush
• hyperhidrosis
• vomiting
• palpitations
• heart rate increased
• dry mouth
• hypertension

Dosing/Administration

Savella is supplied as a tablet designed for oral administration. The recommended initial dose of the drug is 100 mg/day (50 mg twice daily). Dosing should be titrated according to the following schedule:
day 1: 12.5 mg once daily; days 2-3:  25 mg/day (12.5 mg twice daily); days 4-7: 50 mg/day (25 mg twice daily); after day 7: 100 mg/day (50 mg twice daily).

Doses above 200 mg/day have not been studied.

Clinical Trial Results

FDA approval of Savella was based on the results of two clinical trials.

Study 1
This six-month, double-blind, placebo-controlled, multicenter study enrolled adult patients (18-74 years of age). The subjects received daily doses of Savella 100 mg and 200 mg or placebo. The minimum mean baseline pain score of >50 mm on a 100 mm visual analog scale (VAS) ranging from 0 (no pain) to 100 (worst possible pain). The mean baseline pain score in this trial was 69. More patients in the Savella treatment arms experienced at least a 30 percent reduction in pain from baseline (VAS) and considered themselves globally improved (PGIC) than did patients in the placebo arm.

Study 2
This three-month, double-blind, placebo-controlled, multicenter study enrolled adult patients (18-74 years of age). The subjects received daily doses of Savella 100 mg and 200 mg or placebo. The minimum mean baseline pain score was >40 mm on a 100- mm VAS ranging from 0 (no pain) to 100 (worst possible pain). The mean baseline pain score in this trial was 65. improvement. More patients in the Savella treatment arms experienced at least a 30 percent reduction in pain from baseline (VAS) and considered themselves globally improved (PGIC) than did patients in the placebo arm.

In both studies, some patients who rated themselves as globally "much" or "very much" improved experienced a decrease in pain as early as the first week of treatment.