Generic Name

Effexor XR

Mechanism

• Effexor XR (venlafaxine hydrochloride) is a serotonin‑norepinephrine reuptake inhibitor (SNRI).
• It selectively inhibits the reuptake of serotonin (5‑HT) and, at higher concentrations, norepinephrine (NE) by blocking their transporters (SERT and NET).
• Elevates synaptic concentrations of both neurotransmitters, enhancing mood and reducing anxiety symptoms.
• The drug’s extended‑release formulation allows for steady plasma levels, minimizing peak‑to‑trough fluctuations.

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Pharmacokinetics

• Absorption: Oral extended‑release tablets provide ~90 % bioavailability; peak plasma concentrations (Cmax) reached ~4–6 h post‑dose.
• Metabolism: Hepatic via CYP2D6 to active metabolite desvenlafaxine (~10 % of total exposure).
• Elimination: Renal excretion; total half‑life ~5–7 h for venlafaxine, ~7 h for desvenlafaxine.
• Drug interactions: Strong CYP2D6 inhibitors (e.g., fluoxetine) increase venlafaxine levels; CYP2D6 inducers (e.g., carbamazepine) lower exposure.
• Special populations:
• Elderly: minimal change in clearance; monitor for falls.
• Renal impairment: dose adjustment per FDA labeling.
• Hepatic impairment: no dose change required, but monitor for hepatotoxicity.

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Indications

• Major Depressive Disorder (MDD)
• Generalized Anxiety Disorder (GAD)
• Panic Disorder (when combined with cognitive‑behavioral therapy)
• Chronic pain adjunct (e.g., neuropathic pain) – off‑label

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Dosing

• Starting dose:
• Adults: 75 mg/day (XR 37.5 mg at bedtime and 37.5 mg at lunch).
• Elderly or renal impairment: start lower (37.5 mg/day).
• Titration: Increase by 75 mg/day every 4–7 days until therapeutic dose reached.
• Maximum dose: 225 mg/day (XR).
• Administration: Oral, sustained‑release formulation; can be taken with or without food.
• Missed dose: Take when remembered, unless almost time for next dose—skip and continue schedule.

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Monitoring

• Blood pressure: baseline and after each dose increase.
• Electrolytes & renal function: every 4–6 weeks in renal or elderly patients.
• Liver enzymes: baseline, then every 4–6 months in patients on long‑term therapy.
• Serotonin syndrome signs: assess during the first 2–3 weeks of dose escalation.
• Pregnancy tests: for women of childbearing potential.

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Clinical Pearls

• XR Advantage: The extended‑release form reduces the need for twice‑daily dosing and mitigates peak‑related side effects like nausea.
• Monitoring BP: A simple 2‑week surveillance of systolic BP (≥140 mm Hg) can identify hypertensive responders and prevent crisis.
• CYP2D6 genotype check: Poor metabolizers may have higher venlafaxine levels; consider dose reduction or switch to desvenlafaxine.
• Syndrome Triage: Early signs of serotonin syndrome (e.g., clonus or hyperreflexia) should prompt drug discontinuation and consultation.
• Elderly use: While not contraindicated, the risk of falls warrants a cautious titration schedule and evaluation of orthostatic vitals.
• Use in GAD: Studies show a faster onset (2–3 weeks) compared to SSRIs, which may benefit patients with acute anxiety states.

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