desvenlafaxine

General Information

Desvenlafaxine (brand Pristiq) is the primary active metabolite of venlafaxine and an SNRI approved for major depressive disorder.

Because activation does not require CYP2D6, exposure is more predictable across metabolizer phenotypes and drug–drug interaction profiles than venlafaxine.

The compare view, desvenlafaxine evidence feed, and bipolar disorder hub can be used together when aligning taper strategies, monitoring blood pressure effects, and accounting for bipolar-spectrum risk.

Discontinuation symptoms can still occur despite once-daily dosing; predictable taper plans can reduce withdrawal, especially after long-term use.

Clinicians often choose desvenlafaxine after SSRI nonresponse or when venlafaxine’s CYP2D6 interactions are problematic. Blood pressure monitoring and taper planning are key considerations due to dose-related hypertension and withdrawal symptoms. In bipolar-spectrum illness, mood stabiliser coverage is typically maintained, and coordination with the bipolar disorder hub can help clarify relapse-prevention plans.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Inhibits serotonin (SERT) and norepinephrine (NET) transporters, increasing synaptic concentrations of both neurotransmitters.

Minimal affinity for dopaminergic, histaminergic, or muscarinic receptors; norepinephrine contribution plateaus near 100 mg/day.

• SERT and NET inhibition with minimal direct receptor antagonism.

Metabolism and Pharmacokinetics

• Oral bioavailability ≈80%; peak plasma concentrations occur ~7.5 hours after dosing (extended-release).
• Metabolized primarily via UGT conjugation with minor CYP3A4 oxidation; elimination half-life ≈11 hours.
• Approximately 45% excreted unchanged in urine (19% as glucuronide); exposure rises with declining renal function.

Dosing and Administration

• Label dose is 50 mg once daily with or without food; doses >100 mg/day add little efficacy and increase adverse effects.
• Renal impairment: 50 mg every other day for CrCl 30–50 mL/min; 25 mg daily or 50 mg every other day for CrCl <30 mL/min; label recommends avoiding when CrCl <15 mL/min or on hemodialysis.
• Tapering over ≥1–2 weeks can reduce discontinuation symptoms (dizziness, dysesthesias, irritability).
• When discontinuation symptoms occur despite tapering, slower reductions over longer intervals are often better tolerated than larger dose drops.

Monitoring & Labs

• Blood pressure and heart rate at baseline and periodically, especially in patients with pre-existing hypertension.
• Renal function for long-term therapy so dosing remains aligned with kidney function changes over time.
• Discontinuation symptoms during missed doses or tapering; plan refill timing and taper steps are often planned in advance.
• Mood elevation or agitation in bipolar-spectrum illness; coordinate prevention plans via the bipolar disorder hub.

Desvenlafaxine avoids CYP2D6-dependent activation, but blood pressure and taper planning remain the most clinically important follow-up items.

Adverse Effects

Interactions

• Contraindicated with MAOIs or within 7 days of stopping desvenlafaxine (risk of serotonin syndrome).
• Serotonergic agents (SSRIs, SNRIs, triptans, linezolid) increase serotonin syndrome risk—monitoring for agitation, clonus, and autonomic instability is important.
• Additive bleeding risk with NSAIDs, antiplatelets, or anticoagulants.
• Strong CYP3A4 inducers (carbamazepine, rifampin) may lower exposure; clinical response is monitored.

Other Useful Information

• Tablet shell may appear in stool (ghost tablet); reassure patients that medication has been absorbed.
• Renal function is typically checked at baseline and periodically for long-term therapy so dosing stays aligned with kidney function.
• Counseling often covers recognizing serotonin syndrome and when to seek care for sustained hypertension, severe sweating, or emerging mania/hypomania; the bipolar disorder hub includes relapse-prevention resources.
• Benefit typically builds over several weeks; early nausea or sleep disruption may improve with time, dose timing changes, or supportive care.

References

1. Pristiq (desvenlafaxine) prescribing information — DailyMed (2025)
2. CANMAT 2024 Clinical Guidelines for Major Depressive Disorder — Canadian Journal of Psychiatry (2024)
3. Thase2010 Desvenlafaxine
4. Liebowitz2013 Desvenlafaxine MDD