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<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.
Creighton University Medical Center, Omaha, NE 68131, USA. jcg@creighton.edu
J Christopher
JC
Gallagher
Robert A
RA
Strzinek
Ru-fong J
RF
Cheng
Militza K
MK
Ausmanas
Dorothea
D
Astl
Palma
P
Seljan
D000368:Aged; D003511:Cyclohexanols / Q000008:administration & dosage* / Q000009:adverse effects / Q000592:standards; D000069468:Desvenlafaxine Succinate; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000453:epidemiology; D014179:Neurotransmitter Uptake Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000592:standards; D017060:Patient Satisfaction; D017698:Postmenopause; D014666:Vasomotor System / Q000187:drug effects*
D003511:Cyclohexanols; D014179:Neurotransmitter Uptake Inhibitors; D000069468:Desvenlafaxine Succinate