To examine the effects of abruptly withdrawing milnacipran during the 2-week discontinuation phase of a study in which FM patients had received 12 weeks of stable-dose treatment with milnacipran at 100 mg/day.
The effects of withdrawing milnacipran were evaluated prospectively over a 2-week period (Weeks 12 to 14) using a randomized, placebo-controlled withdrawal design. Patients who had originally received milnacipran 100 mg/d for 12 weeks were re-randomized to continue milnacipran (n = 178) or switch directly to placebo (n = 178); patients originally receiving placebo continued placebo (n = 359).
Clinicalstrials.gov (NCT00314249).
Loss of efficacy was evaluated by mean changes in pain and functional measures and by percentage of composite responders, defined as patients with simultaneous improvements in pain, global status, and physical functioning. Newly emergent adverse events and changes in vital signs were also recorded.
Within 2 weeks,patients switched from milnacipran to placebo had greater mean worsening in pain, functioning, and global status measures when compared with patients continuing treatment. In addition, significantly fewer composite responders were found in patients who discontinued active treatment than in patients who continued receiving milnacipran (22.0% vs 32.3%, p < 0.05). Incidences of newly emergent adverse events were 16.3% and 18.0% in patients discontinuing and continuing treatment, respectively. Mean vital sign changes decreased or returned to baseline within 2 weeks of discontinuation.
Patients discontinuing milnacipran experienced worsening in multiple efficacy parameters within 2 weeks. Vital sign changes observed with milnacipran during the 12-week stable-dose period decreased or returned to baseline values within 2 weeks after discontinuation of treatment. No new safety concerns were found during this discontinuation period with milnacipran.