Venlafaxine
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Venlafaxine
Effexor XR, Effexor IR (discontinued in US, generic widely available)
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Summary
Common uses
Major depressive disorder (FDA)0, Generalized anxiety disorder (FDA)0, Social anxiety disorder (FDA)0, Panic disorder (FDA)0, Posttraumatic stress disorder (off-label)0, Neuropathic pain (off-label)0, Menopausal vasomotor symptoms (off-label, evidence-supported)0
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[2]
Bioavailability
~45%[2]
Pregnancy
Observational signal for neonatal adaptation syndrome with late-pregnancy exposure; weigh against the risks of untreated maternal depression.[citation needed]
Legal status
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).[1] 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.
References
- ↑ PharmGKB: Venlafaxine pharmacogenomics annotations. https://www.pharmgkb.org/chemical/PA451866
- ↑ 2.0 2.1 2.2 FDA Prescribing Information, Effexor XR (venlafaxine extended-release), Wyeth/Pfizer, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020699s107lbl.pdf