Venlafaxine

Serotonin-norepinephrine reuptake inhibitor (SNRI), Antidepressant, Anxiolytic

Venlafaxine

Effexor XR, Effexor IR (discontinued in US, generic widely available)

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Summary

Classes

Serotonin-norepinephrine reuptake inhibitor (SNRI), Antidepressant, Anxiolytic

Pharmacy

Starting dose

XR 37.5 mg PO once daily for 4-7 days, then 75 mg/day; titrate by 75 mg every ≥4 days to clinical effect. IR 25-37.5 mg BID-TID

Preparations

IR tablets 25, 37.5, 50, 75, 100 mg; XR capsules 37.5, 75, 150, 225 mg

US FDA Max

225 mg/day outpatient (XR); 375 mg/day inpatient (IR divided TID); 75 mg/day in moderate hepatic impairment

Pharmacology

Routes

Oral

Onset

Antidepressant effect over 1-2 weeks; anxiolytic effect over 4-6 weeks

Duration

24 hours (XR); 12 hours (IR)

Half-life

Venlafaxine 5 hours; desvenlafaxine active metabolite 11 hours

Bioavailability

~45%

Pregnancy

Observational signal for neonatal adaptation syndrome with late-pregnancy exposure; weigh against the risks of untreated maternal depression.^{[citation needed]}

Legal status

Rx-only in US. Carries the antidepressant Boxed Warning for suicidality in children, adolescents, and young adults

Purported mechanism

Serotonin and norepinephrine reuptake inhibitor with predominantly serotonergic activity at lower doses (37.5-150 mg); the noradrenergic effect adds at higher doses (>150 mg) and the dual-mechanism advantage really emerges then. The active metabolite desvenlafaxine (separately marketed as Pristiq) contributes meaningfully to clinical effect.▲0▼ Severe discontinuation syndrome is the marquee adverse-effect feature: venlafaxine's short half-life produces intense flu-like symptoms, dizziness, electric-shock sensations ("brain zaps"), and emotional dysregulation on abrupt discontinuation, worse than most other SNRIs and SSRIs. Slow taper essential. Dose-dependent diastolic hypertension at higher doses; routine BP monitoring at dose escalation. CYP2D6 substrate; CYP2D6 oxidation produces the active metabolite desvenlafaxine. PharmGKB clinical annotations for venlafaxine apply (Level 2A). No formal CPIC guideline covers venlafaxine; the CPIC SSRI/CYP2D6 guideline (Hicks 2015) covers sertraline, citalopram, escitalopram, fluoxetine, fluvoxamine, and paroxetine and does not extend to SNRIs.