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Desvenlafaxine (Pristiq)

SNRI • Last reviewed 2025-09-26

General information

Desvenlafaxine is the active metabolite of venlafaxine and an SNRI approved for the treatment of major depressive disorder. It offers linear pharmacokinetics, minimal CYP2D6 dependence, and consistent exposure across metabolizer phenotypes.

Extended-release tablets (25, 50, 100 mg) allow once-daily administration with or without food. The 50 mg dose delivers near-maximal serotonin and norepinephrine transporter occupancy, limiting the need for routine up-titration.

Blood pressure elevations, hyperhidrosis, and gastrointestinal side effects are dose-related. Because renal clearance accounts for ~45% unchanged drug elimination, dose reductions are recommended when creatinine clearance falls below 50 mL/min.

Clinical guidelines position desvenlafaxine as a reasonable SNRI alternative after SSRI nonresponse or when venlafaxine-related CYP interactions are a concern.

Dosing & administration

Start and maintain 50 mg once daily.

Consider 25 mg once daily for severe renal impairment (CrCl <30 mL/min).

Avoid doses >100 mg/day; higher doses offer minimal additional efficacy with more adverse effects.

Mechanism of action

Potent inhibition of serotonin and norepinephrine transporters with minimal muscarinic, histamine, or adrenergic receptor affinity.

Metabolism & pharmacokinetics

Oral bioavailability is ~80%. Peak plasma concentrations occur in ~7.5 hours. Metabolized primarily via UGT conjugation with minor CYP3A4 oxidation; ~45% eliminated unchanged in urine. Half-life ~11 hours (longer in renal impairment).

Drug interactions

Avoid MAOIs, linezolid, or methylene blue (serotonin syndrome).

Serotonergic agents increase serotonin syndrome risk; monitor closely.

Strong CYP3A4 inducers (carbamazepine) may reduce exposure; consider alternatives.

Monitoring & safety checks

  • Blood pressure/pulse at baseline and periodically

  • Renal function to guide dosing

  • Assess for suicidality or manic switch

Discontinuation guidance

Taper gradually over ≥2 weeks; withdrawal symptoms resemble venlafaxine and may include dizziness, nausea, and dysesthesias.

References

  1. Desvenlafaxine Prescribing Information — DailyMed
  2. CANMAT 2024 Depression Guidelines (2024)
  3. Desvenlafaxine in the treatment of major depressive disorder — CNS Drugs (2019)

Educational use only — verify details in current prescribing information and authoritative clinical guidelines before making prescribing decisions.