Desvenlafaxine: a new serotonin-norepinephrine reuptake inhibitor for the treatment of adults with major depressive disorder.
BACKGROUND
Desvenlafaxine succinate, a serotonin-norepinephrine reuptake inhibitor (SNRI), was approved by the US Food and Drug Administration (FDA) in February 2008 for the treatment of adult patients with major depressive disorder (MDD). Desvenlafaxine is the third SNRI approved by the FDA for this indication.


OBJECTIVE
This article reviews the available information for desvenlafaxine, focusing on its pharmacodynamics, pharmacokinetics, clinical efficacy, and safety profile.


METHODS
A comprehensive search of MEDLINE (1950-March 2009), International Pharmaceutical Abstracts (1970-March 2009), ISI Web of Knowledge (1996-March 2009), and EMBASE (1974-March 2009) was conducted using the terms desvenlafaxine, O-desmethylvenlafaxine, and Pristiq. Reference lists of articles were reviewed for other relevant publications. Abstracts of unpublished clinical studies presented at the American Psychiatric Association annual meetings (2004-2008) were included in the review; also included were data from the FDA and the European Medicines Agency Web sites.


RESULTS
After oral administration, desvenlafaxine reaches T(max) in 7 to 8 hours and is slowly eliminated, with t((1/2)) values of 9 to 15 hours. With once-daily dosing, steady-state plasma concentrations are achieved within 4 to 5 days. Alternate-day dosing should be implemented in patients with severe renal impairment (creatinine clearance, < or =30 mL/min) and those with end-stage renal disease. In patients with moderate to severe hepatic impairment, daily doses should not exceed 100 mg. Nine short-term studies of desvenlafaxine have been conducted but only 8 were published. These 8 clinical studies evaluated oral desvenlafaxine 50 to 400 mg/d using randomized controlled trials for the treatment of MDD in adult outpatients. Significantly greater efficacy in the reduction of depressive symptoms was found in patients taking desvenlafaxine 50 mg/d (P < 0.05) compared with placebo. No additional therapeutic benefits were found at doses >50 mg/d. Preliminary data support desvenlafaxine's efficacy and tolerability in the treatment of menopause-associated vasomotor symptoms. Desvenlafaxine was generally well tolerated in clinical trials; the most common adverse events were nausea, suicidal ideation, and changes in blood pressure and weight.


CONCLUSIONS
Desvenlafaxine 50 mg/d has been found to be efficacious and generally well tolerated in short-term trials for the treatment of adults with MDD. Further studies are needed to determine des-venlafaxine's role in the management of MDD and its efficacy compared with other antidepressants.
Perry
Richard
R
Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York 11201, USA. Perry@UU.edu
Cassagnol
Manouchkathe
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019540:Area Under Curve; D003511:Cyclohexanols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D000069468:Desvenlafaxine Succinate; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D014179:Neurotransmitter Uptake Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011247:Pregnancy
D000928:Antidepressive Agents; D003511:Cyclohexanols; D014179:Neurotransmitter Uptake Inhibitors; D000069468:Desvenlafaxine Succinate