Pharmacologic class:

Antidepressant (serotonin and norepinephrine reuptake inhibitor [SNRI])

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Active ingredient:

Desvenlafaxine (as succinate) 50 mg, 100 mg; extended-release tabs.


Major depressive disorder (MDD).


Desvenlafaxine, the major active metabolite of venlafaxine (Effexor XR, also from Wyeth), is a potent and selective SNRI. The increase in the effects of these neurotransmitters in the central nervous system (CNS) may be responsible for its clinical efficacy.

Desvenlafaxine is primarily metabolized by conjugation (mediated by UGT isoforms) and, to a minor extent, through oxidative metabolism mediated by the CYP3A4 enzyme; the CYP2D6 metabolic pathway is not involved. It is eliminated primarily by the kidneys.

Clinical trials:

Four eight-week, double-blind, placebo-controlled fixed-dose studies were conducted to assess the efficacy and safety of desvenlafaxine in treating MDD. The first study compared desvenlafaxine 100 mg, 200 mg, and 400 mg once daily with placebo. In a second study, patients received desvenlafaxine 200 mg or 400 mg once daily or placebo, and in two other studies, patients were given desvenlafaxine 50 mg or 100 mg once daily or placebo. Desvenlafaxine was shown to be better than placebo, as measured by improvement using the 17-item Hamilton Rating Scale for Depression score in four studies, and it was better than placebo in overall improvement (measured by the Clinical Global Impressions Scale—Improvement) in three of the four studies. Doses >50 mg/day were not shown to be more effective, but adverse reactions and discontinuations were more frequent at the higher dose.


Swallow whole. 50 mg once daily. Severe renal impairment (creatinine clearance <30 mL/min), end-stage renal disease: 50 mg every other day. Do not give supplemental dose after dialysis. Moderate renal impairment: maximum 50 mg/day. Hepatic impairment: maximum 100 mg/day. Withdraw gradually.


Not recommended.


Monoamine oxidase inhibitors (MAOIs): see Interactions.


Monitor BP; reduce dose or discontinue if elevated BP persists. Cardio- or cerebrovascular disease. Hypercholesterolemia. Increased intraocular pressure. Mania/hypomania. Severe renal dysfunction. Seizure disorder. Re-evaluate periodically. Suicidal ideation. Write prescription for smallest practical amount. Elderly. Labor and delivery. Pregnancy (Cat. C; avoid in third trimester; taper). Nursing mothers: not recommended.


Allow ≥14 days after MAOI discontinuance before starting desvenlafaxine; allow ³7 days after desvenlafaxine discontinuance before starting an MAOI. Avoid alcohol, concomitant venlafaxine, other forms of desvenlafaxine. Concomitant serotonin precursors (e.g., tryptophan): not recommended. May potentiate anticoagulants. Monitor for serotonin syndrome with selective serotonin reuptake inhibitors, SNRIs, triptans. May be potentiated by potent CYP3A4 inhibitors. May antagonize CYP3A4 substrates. Caution with serotonergics, other CNS-active drugs.

Adverse reactions:

GI upset, dizziness, insomnia, hyperhidrosis, constipation, somnolence, decreased appetite, anxiety, sexual dysfunction; rare:hyponatremia/syndrome of inappropriate antidiuretic hormone (especially in elderly), interstitial lung disease, eosinophilic pneumonia, serotonin syndrome, mydriasis.

How supplied:

Tabs—14, 30, 90.

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