Clinical utility of desvenlafaxine 50 mg/d for treating MDD: a review of two
randomized placebo-controlled trials for the practicing physician.
Author(s): Reddy S, Kane C, Pitrosky B, Musgnung J, Ninan PT, Guico-Pabia CJ.
Affiliation(s): Pfizer, formerly Wyeth Research, Collegeville, Pennsylvania 19426, USA.
reddys5@wyeth.com
Publication date & source: 2010, Curr Med Res Opin. , 26(1):139-50
BACKGROUND: Major depressive disorder (MDD) is a common, seriously impairing
illness. Desvenlafaxine (administered as desvenlafaxine succinate) is the third
serotonin-norepinephrine reuptake inhibitor (SNRI) approved in the United States
for the treatment of MDD. Short-term clinical studies have demonstrated the
efficacy and safety of 50 to 400 mg/d doses, with no evidence that doses greater
than 50 mg/d confer additional benefit.
OBJECTIVE: This paper summarizes published data on the efficacy, safety, and
tolerability of the desvenlafaxine 50-mg/d recommended therapeutic dose for MDD
and discusses clinical practice considerations.
METHODS: A systematic review of MEDLINE, PsycINFO, and PubMed (all years through
June 2009) was performed using the terms desvenlafaxine, DVS, and ODV. The
criteria for inclusion in the review were a double-blind design, a placebo
control or active comparator group, the 50-mg desvenlafaxine dose group, and
enrollment of patients with a diagnosis of MDD. Posters were included if they
reported on a study that was subsequently published in a manuscript.
RESULTS: Overall results of two randomized, placebo-controlled, 8-week clinical
trials demonstrated the efficacy of desvenlafaxine 50 mg/d for MDD. Statistically
significant improvements compared with placebo were observed on the primary
efficacy measure (17-item Hamilton Rating Scale for Depression [HAM-D(17)] total
score; P < 0.05). Significant differences were observed on several secondary
measures (Montgomery Asberg Depression Rating Scale scores in both trials [P <
0.05]; Clinical Global Impressions-Improvement scores [P < or = 0.01], Clinical
Global Impressions-Severity scores [P < or = 0.01], HAM-D(17) response [P < or =
0.01] and remission [P < 0.05] in one trial each). Functional outcomes measures
(Sheehan Disability Scale total and World Health Organization 5-Item Well-Being
Index scores) were significant in both trials (P < 0.05). Safety results indicate
desvenlafaxine treatment was safe and well tolerated; findings were consistent
with the SNRI class. The generalizability of these findings is limited by the
study protocols, which excluded patients with unstable comorbid medical
conditions and also those with other Axis 1 and 2 psychiatric illnesses.
Additionally, comparisons with other SNRIs are challenging given differences in
study design. Desvenlafaxine can be initiated with the 50-mg/d therapeutic dose
without titration and provides efficacy with rates of discontinuation due to
treatment-emergent adverse events similar to placebo. In vitro data indicate
desvenlafaxine has minimal inhibitory effects on cytochrome P450 (CYP) 2D6 and
clinical studies show desvenlafaxine does not have a clinically relevant effect
on CYP2D6 metabolism. In vitro data also indicate desvenlafaxine is not a
substrate or inhibitor of the p-glycoprotein transporter. Plasma protein binding
of desvenlafaxine is low (30%) and independent of drug concentration.
Bioavailability is high at 80% after oral administration and is not affected by
food.
CONCLUSIONS: Desvenlafaxine 50 mg/d has demonstrated efficacy, safety, and
tolerability for the treatment of MDD in two placebo-controlled trials. The
metabolic profile of desvenlafaxine suggests a low risk of drug-drug interactions
owing to minimal inhibitory effects on CYP2D6, lack of interaction with
p-glycoprotein, and low protein binding.
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