Desvenlafaxine for major depressive disorder: incremental clinical benefits from a second-generation serotonin-norepinephrine reuptake inhibitor.
BACKGROUND
genetic and pharmacologically-driven variations in common mechanisms involved in the disposition of antidepressant medications may contribute to variable interpatient response. This review describes the pharmacological properties underlying the safety and efficacy of desvenlafaxine, a second-generation serotonin-norepinephrine reuptake inhibitor (SNRI).


METHODS
literature published between January 2006 and September 2010 evaluating desvenlafaxine was reviewed.


BACKGROUND
Desvenlafaxine therapy is initiated at the therapeutic dose (50 mg/day) without a need for dose titration. Desvenlafaxine metabolism and distribution are not appreciably affected by altered function of cytochrome P450 (CYP) enzymes or permeability glycoprotein (P-gp). Desvenlafaxine has clinically insignificant effects on the activity of CYP and P-gp. The efficacy of desvenlafaxine in treating major depressive disorder has been established. Adverse events are characteristic of the SNRI class. Notably, the rate of discontinuation due to adverse events with the 50 mg/day recommended therapeutic dose is comparable to that seen with placebo.


CONCLUSIONS
incremental benefits with desvenlafaxine, derived from straight-forward dosing, a simple metabolic profile and lack of interaction with active transporter P-gp and CYP enzymes may contribute to more consistent response, good tolerability and lower incidence of drug-drug interactions with concomitant medications.
Pfizer, Inc., (formerly Wyeth Research), Collegeville, PA 19426, USA. Alice.Nichols@pfizer.com
Alice I
AI
Nichols
Karen A
KA
Tourian
Susanna Y
SY
Tse
Jeffrey
J
Paul
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003511:Cyclohexanols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D000069468:Desvenlafaxine Succinate; D004347:Drug Interactions; D006801:Humans; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D003511:Cyclohexanols; D003577:Cytochrome P-450 Enzyme System; D000069468:Desvenlafaxine Succinate; D017367:Selective Serotonin Reuptake Inhibitors