PALM SPRINGS, CA — Patients with fibromyalgia who have an inadequate response to duloxetine may gain additional benefit in global status and pain improvement when switched to milnacipran, according to research presented at the 2012 American Academy of Pain Medicine Annual Meeting.
It is common for patients with fibromyalgia to switch therapies during treatment in order to gain therapeutic benefit or avoid certain side effects. Milnacipran and duloxetine, both dual serotonin and norepinephrine reuptake inhibitors (SNRIs) approved to manage fibromyalgia, differ in pharmacologic properties and adverse-effect profiles.
Lucinda Bateman, MD, of The Fatigue Consultation Clinic, Salt Lake City, UT, and colleagues conducted a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and efficacy of milnacipran in 100 patients who were previously unresponsive to duloxetine. Study inclusion criteria were limited to a diagnosis of fibromyalgia; male or female outpatients between ages 18–70 years; stable treatment with duloxetine 60mg/day for ≥4 weeks prior to screening; and baseline initial dosage at 100mg/day, with a possible adjustment from 50mg/day to 200mg/day.
Participants received duloxetine 60mg/day during a two-week open-label period. Those who had a one-week recall visual analog scale (VAS) pain score ≥40 who were dissatisfied with duloxetine treatment were randomized 4:1 to be switched to milnacipran (n=86) or placebo (n=21) for ten weeks. The placebo arm, though small by design, was intended to minimize expectation bias. Patients randomized to milnacipran 100mg/day were switched directly from duloxetine with no tapering or titration periods, and those randomized to placebo had their duloxetine dosage reduced to 30mg/day for one week before switching.
After ten weeks of treatment, 32.9% (26/79) of patients who switched to milnacipran were much improved or very much improved, thus reaching Patient Global Impression of Change (PGIC) responder status, compared to 5 of 21 patients taking placebo. In addition, patients taking milnacipran had a 12.3mm (19%) improvement from baseline in VAS pain scores at ten weeks after treatment. One-quarter of patients switched to milnacipran experienced ≥50% pain improvement during the double-blind treatment period, and more than one-third had ≥30% pain improvement during post-hoc analysis.
Treatment-emergent adverse events (TEAEs) were reported by 74.1% of patients switched from duloxetine to milnacipran compared to 76.2% of patients switched from duloxetine to placebo. In total, 15 patients (17.6%) switched to milnacipran discontinued due to adverse events (AEs). Common AEs included dizziness (3 patients); fatigue, irritability, hypersensitivity, dizziness postural, anxiety, restlessness, depression, mood swings, insomnia, suicidal ideation, and dysuria (1 patient each); or rash (2 patients). In the placebo group, 9.5% (2 patients) discontinued due to either nausea or contact dermatitis.
Two patients switched from duloxetine to milnacipran had a potentially significant increase in sitting diastolic blood pressure (≥110mm Hg and increase ≥10mm Hg), and one patient switched to milnacipran experienced weight loss of ≥7%.
“These results suggest that fibromyalgia patients with an inadequate response to duloxetine treatment may gain additional benefit in global status and pain improvement when switched to milnacipran for management of their symptoms,” the researchers concluded. A direct switch from duloxetine to milnacipran did not result in any new safety or tolerability concerns, they added.