Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of milnacipran and evaluate relevant clinical trial data.
Data sources: MEDLINE, International Pharmaceutical Abstracts, and Google Scholar searches (1966-June 2010) were conducted using the key words fibromyalgia, milnacipran, and serotonin-norepinephrine reuptake inhibitor. Searches were limited to articles published in English.
Study selection and data extraction: All available English-language articles of human studies were evaluated. One pharmacokinetic study reviewed included animal data. References cited in identified articles were used for additional evaluation.
Data synthesis: Milnacipran is a serotonin-norepinephrine reuptake inhibitor with a 3-fold increased selectivity for norepinephrine compared to serotonin. It is well absorbed with 85-90% bioavailability. Maximum concentrations are achieved 2-4 hours after administration. Milnacipran does not undergo cytochrome P450 metabolism and has a half-life of 6-8 hours. Fifty-five percent of each dose is excreted unchanged in the urine. Dose adjustment is needed in patients with an estimated creatinine clearance of <30 mL/min. Clinical trials indicated that twice-daily dosing at 100 mg/day or 200 mg/day was superior to single-daily dosing. Studies further established the effectiveness of both doses in the treatment of fibromyalgia pain utilizing patient self-reported pain scores, as well as on a visual analog scale, Patient Global Impression of Change scale, and the Short-Form 36 Physical Component Summary. A 6-month extension trial, which evaluated patients continued on milnacipran for up to 1 year, demonstrated continued pain relief. The most common adverse drug reaction associated with milnacipran was nausea, which was reduced with slow-dose titration and administration with food.
Conclusions: Milnacipran is an effective treatment option for patients with fibromyalgia. More head-to-head clinical trials are necessary to assess its ultimate place in therapy.