The effect of dose titration and dose tapering on the tolerability of desvenlafaxine in women with vasomotor symptoms associated with menopause

Objective: To determine whether titrating up and tapering down of desvenlafaxine (administered as desvenlafaxine succinate) improves its tolerability in postmenopausal women with vasomotor symptoms (VMS). Methods: In the 1-week titration phase, participants received desvenlafaxine 100 mg/d (no titration), desvenlafaxine 50 mg/d, desvenlafaxine 25 mg/d (4 days) then 50 mg/d (3 days), or desvenlafaxine 25 mg/d. Participants then received open-label desvenlafaxine 100 mg/d for 15 weeks. In the 2-week taper phase, participants received placebo, desvenlafaxine 50 mg/d then placebo (7 days each), desvenlafaxine 50 mg/d then 25 mg/d (7 days each), or desvenlafaxine 50 mg/d every other day. Primary endpoints included nausea incidence during the first 2 weeks of treatment and Discontinuation-Emergent Signs and Symptoms (DESS) Checklist total scores after taper weeks 1 and 2. Results: Nausea incidence was significantly lower for the desvenlafaxine 25 mg/d (19%) and 50 mg/d (22.6%) titration regimens vs. no titration (35.2%; p=0.004 and p=0.035, respectively). At taper week 1, mean DESS scores were significantly lower for desvenlafaxine 50 mg every other day (2.26, p