Generic Name

Pristiq

Mechanism

• Selective inhibition of serotonin (5‑HT) and norepinephrine (NE) reuptake
• Potently blocks the serotonin transporter (SERT) and norepinephrine transporter (NET).
• IC50 values: SERT ~ 44 nM, NET ~ 152 nM, indicating balanced dual‑transport inhibition.
• Leads to increased extracellular concentrations of 5‑HT and NE, improving monoaminergic signaling implicated in MDD pathophysiology.
• Lacks activity at dopamine transporters, reducing potential for dopaminergic side effects.

Pharmacokinetics

Indications

• Major depressive disorder (adult and pediatric; FDA‑approved for ≥18 y; off‑label for <18 y).
• Often used when patients are intolerant or refractory to selective serotonin reuptake inhibitors (SSRIs) or tricyclics.

Contraindications

• Contraindications:
• Concurrent use with monoamine oxidase inhibitors (MAOIs) or history of serotonin syndrome.
• Hypersensitivity to desvenlafaxine or any excipients.
• Warnings:
• Hypertension: monitor BP; risk of rising systolic pressure.
• Serotonin syndrome: especially when combined with SSRIs, trazodone, or triptans.
• Seizure risk: increased at doses >100 mg/day or in patients with epilepsy.
• Pregnancy/Breastfeeding: Category C; use only if benefits outweigh risks.
• Precautions:
• Hepatic disease: safe in mild impairment; avoid in severe disease.
• renal impairment: dose adjustment required for severe CKD; monitor.

Dosing

• Starting dose: 50 mg once daily in the evening (or morning if insomnia is an issue).
• Titration:
• After 2–4 weeks if inadequate response → increase to 100 mg daily.
• Maximum recommended dose: 100 mg/day.
• Re‑initiation after discontinuation >4 weeks: Restart at 50 mg daily; titrate as above.
• Administration: Take with a full glass of water; may be taken with or without food (food does not affect absorption).
• Missed dose: Take as soon as remembered; do not double the next dose.

Adverse Effects

• Management cues:
• GI symptoms: take with food, consider antiemetics.
• Hypertension: check BP at baseline, week 2, week 4, and monthly thereafter.
• Suicidal ideation: monitor especially during the first 12 weeks or after dose changes.

Monitoring

• Baseline:
• Blood pressure (BP) and heart rate (HR).
• Weight, BMI.
• Renal function (serum creatinine, eGFR).
• Liver enzymes if hepatic disease suspected.
• Follow‑up:
• BP/HR at 2 weeks, 4 weeks, and monthly thereafter.
• Weight at each visit.
• Monitoring for signs of serotonin syndrome or increased suicidality, particularly in adolescents/young adults.
• Laboratory:
• Routine labs only if comorbidities suspected; no routine monitoring of desvenafaxine plasma levels.

Clinical Pearls

• Low CYP profile: Desvenlafaxine’s minimal CYP interactions make it a safer choice in patients on polypharmacy (e.g., antidepressant + psychotropic).
• Kidney‑friendly in mild‑to‑moderate CKD: Unlike many SNRIs, only a small dose adjustment is needed for eGFR ≥30 ml/min; negligible hepatic dose changes.
• Titration speed: Because of the 11‑hour half‑life, a steady state is reached in approximately one week; dose escalation can be performed at two‑week intervals, reducing the risk of rebound hypertension.
• Insomnia management: If insomnia occurs, administer the evening dose; otherwise, shift to the morning to avoid sleep disruption.
• Serotonin syndrome screening: Even with a balanced SNRI, overlapping serotonergic agents (e.g., triptans, linezolid) can precipitate syndrome; always review the drug list when adding new serotonergic therapy.
• Weight change counseling: Many patients report weight loss; counsel that this is desirable for overweight patients but monitor for unintended significant weight loss.
• Elderly patients: Start at the lowest dose (50 mg) to mitigate orthostatic hypotension; monitor cognition and falls risk.

These concise, evidence‑based points provide clinicians and trainees with a quick reference for prescribing, monitoring, and troubleshooting Pristiq in contemporary practice.