The effect of dose titration and dose tapering on the tolerability of
desvenlafaxine in women with vasomotor symptoms associated with menopause.
Author(s): Gallagher JC, Strzinek RA, Cheng RF, Ausmanas MK, Astl D, Seljan P.
Affiliation(s): Creighton University Medical Center, Omaha, NE 68131, USA. jcg@creighton.edu
Publication date & source: 2012, J Womens Health (Larchmt). , 21(2):188-98
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<0.001), 50/25 mg/d (2.28,
p<0.001), and 50 mg/d-placebo (1.84, p<0.001) taper regimens vs. no taper (7.07).
At week 2, the mean DESS total score was significantly higher for the
desvenlafaxine 50 mg/d-placebo regimen vs. no taper (4.46 vs. 2.44, respectively;
p=0.009). Desvenlafaxine 50 mg every other day was the least tolerated of the
taper regimens.
CONCLUSIONS: Titration regimens may improve tolerability of desvenlafaxine 100
mg/d in postmenopausal women with VMS. Taper regimens of desvenlafaxine 50
mg/d-placebo or 50/25-mg/d, were better tolerated than abrupt discontinuation or
desvenlafaxine 50 mg given every other day taper regimen.
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