Key result
Supratherapeutic doses of milnacipran (300 mg bid) did not cause QT prolongation in healthy volunteers, showing a maximum baseline-adjusted QTcNi difference of -4.7 ms versus placebo.
Why the study?
Does milnacipran affect cardiac repolarization and prolong the QT interval in healthy participants?
RCT (n=100)
Double-blind
Does milnacipran affect cardiac repolarization and prolong the QT interval in healthy participants?
Mean Difference: -4.7 (95% CI -9.4–-0.1)
Milnacipran at supratherapeutic doses does not significantly affect cardiac repolarization or cause QT prolongation in healthy participants.
Supports milnacipran cardiac safety at high doses without QT monitoring; confirms no repolarization effect in RCT evidence.
Milnacipran is approved for management of fibromyalgia in the United States. In this double-blind, placebo- and active drug-controlled study (N = 100), effects of supratherapeutic doses of milnacipran on cardiac repolarization were evaluated in healthy volunteers. The primary outcome was the largest mean difference between milnacipran and placebo in time-matched baseline-adjusted QT interval corrected for heart rate using an individual correction formula (QTcNi). In addition, data were analyzed using the Fridericia formula (QTcF) and a post hoc piecewise QTcNi analysis based on a dichotomous cut of RR interval data at 800 ms. Moxifloxacin (400 mg single dose) was used to establish assay sensitivity. Using the QTcNi method, the largest difference in baseline-adjusted QTcNi between milnacipran 300 mg bid and placebo was -4.7 ms (90% confidence interval [CI]: -9.4 to -0.1), indicating no QT prolongation. Analysis using the Fridericia formula (QTcF) showed a maximum adjusted mean change of +7.7 ms, but QTcF versus RR interval plots indicated overcorrection with this method. The piecewise QTcNi correction method demonstrated a more accurate correction for drug-induced heart rate increase; mean baseline-adjusted between-group difference was +0.9 ms (90% CI: -6.6 to 8.3). The results suggest that milnacipran would not significantly affect cardiac repolarization at clinically relevant therapeutic and supratherapeutic concentrations.
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Periclou et al. (2010) conducted an RCT in Healthy (n=100). Milnacipran vs. Placebo was evaluated on Largest mean difference between milnacipran and placebo in time-matched baseline-adjusted QT interval corrected for heart rate using an individual correction formula (QTcNi) (MD -4.7 ms, 95% CI -9.4 to -0.1). Supratherapeutic doses of milnacipran (300 mg bid) did not cause QT prolongation in healthy volunteers, showing a maximum baseline-adjusted QTcNi difference of -4.7 ms versus placebo.
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