Milnacipran for the management of fibromyalgia syndrome

Abstract

Fibromyalgia syndrome (FMS) is a widespread pain condition associated with fatigue, cognitive dysfunction, sleep disturbance, depression, anxiety, and stiffness. Milnacipran is one of three medications currently approved by the Food and Drug Administration in the United States for the management of adult FMS patients. This review is the second in a three-part series reviewing each of the approved FMS drugs and serves as a primer on the use of milnacipran in FMS treatment including information on pharmacology, pharmacokinetics, safety and tolerability. Milnacipran is a mixed serotonin and norepinephrine reuptake inhibitor thought to improve FMS symptoms by increasing neurotransmitter levels in descending central nervous system inhibitory pathways. Milnacipran has proven efficacy in managing global FMS symptoms and pain as well as improving symptoms of fatigue and cognitive dysfunction without affecting sleep. Due to its antidepressant activity, milnacipran can also be beneficial to FMS patients with coexisting depression. However, side effects can limit milnacipran tolerability in FMS patients due to its association with headache, nausea, tachycardia, hyper- and hypotension, and increased risk for bleeding and suicidality in at-risk patients. Tolerability can be maximized by starting at low dose and slowly up-titrating if needed. As with all medications used in FMS management, milnacipran works best when used as part of an individualized treatment regimen that includes resistance and aerobic exercise, patient education and behavioral therapies.

Systemic and Brain Pharmacokinetics of Milnacipran in Mice: Comparison of Intraperitoneal and Intravenous Administration

“…Milnacipran’s metabolism primarily involves hepatic pathways (limited involvement of CYP enzymes), with ≤30% undergoing glucuronidation, ≤20% undergoing oxidative metabolism, and ≥50% being eliminated unchanged in the urine. Milnacipran can be used without dose adjustment in patients with mild to moderate renal insufficiency (CrCl ≥ 30 mL/min), but in patients with severe renal impairment (CrCl 5 to 29 mL/min), a 50% dose reduction is advised [ 41 ].…”

Update on Treatment Guideline in Fibromyalgia Syndrome with Focus on Pharmacology

“…Milnacipran (MLN) has three-fold stronger effect on noradrenalin than serotonin. It is recommended by EULAR (seven systematic reviews) and has been shown to be effective [ 21 , 23 , 24 , 25 , 26 ], though DLX was found to be superior to MLN in reducing pain and sleep problems [ 27 ]. AWMF guidelines do not recommend the use of MLN.…”

“…There was no significant effect at 20–30 mg/day and no difference between 60 mg and 120 mg /day. Ormseth, M.J. et al 2010 [ 24 ] Review article. MLN has a demonstrated efficacy in managing global FMS symptoms and pain at doses of 100 and 200 mg divided twice daily however it has numerous side effects.…”