Efficacy of milnacipran in patients with fibromyalgia.
OBJECTIVE
Fibromyalgia (FM) is a common musculoskeletal condition characterized by widespread pain, tenderness, and a variety of other somatic symptoms. Current treatments are modestly effective. Arguably, the best studied and most effective compounds are tricyclic antidepressants (TCA). Milnacipran, a nontricyclic compound that inhibits the reuptake of both serotonin and norepinephrine, may provide many of the beneficial effects of TCA with a superior side effect profile.


METHODS
One hundred twenty-five patients with FM were randomly assigned in a 3:3:2 ratio to receive milnacipran twice daily, milnacipran once daily, or placebo for 3 months in a double-blind dose-escalation trial; 92% of twice-daily and 81% of once-daily participants achieved dose escalation to the target milnacipran dose of 200 mg.


RESULTS
The primary endpoint was reduction of pain. Both the once- and twice-daily groups showed statistically significant improvements in pain, as well as improvements in global well being, fatigue, and other domains. Response rates for patients receiving milnacipran were equal in patients with and without comorbid depression, but placebo response rates were considerably higher in depressed patients, leading to significantly greater overall efficacy in the nondepressed group.


CONCLUSIONS
In this Phase II study, milnacipran led to statistically significant improvements in pain and other symptoms of FM. The effect sizes were equal to those previously found with TCA, and the drug was generally well tolerated.
Gendreau
R Michael
RM
Cypress Biosciences, 4350 Executive Drive, San Diego, CA 92121, USA. mgendreau1@cypressbio.com
Thorn
Michael D
MD
Gendreau
Judy F
JF
Kranzler
Jay D
JD
Ribeiro
Saulo
S
Gracely
Richard H
RH
Williams
David A
DA
Mease
Philip J
PJ
McLean
Samuel A
SA
Clauw
Daniel J
DJ
D000700:Analgesics / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D003521:Cyclopropanes / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005356:Fibromyalgia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078764:Milnacipran; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control*; D010147:Pain Measurement; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D018434:Sickness Impact Profile; D016896:Treatment Outcome
D000700:Analgesics; D000929:Antidepressive Agents, Tricyclic; D003521:Cyclopropanes; D000078764:Milnacipran; D017367:Selective Serotonin Reuptake Inhibitors