Maximum Dose of Venlafaxine ER
The maximum dose of venlafaxine ER is 375 mg/day, though routine outpatient depression typically requires no more than 225 mg/day. 1
Standard Maximum Dosing
- The FDA-approved maximum dose is 375 mg/day for severe depression, typically administered in divided doses. 1
- For routine outpatient depression, doses above 225 mg/day showed no additional benefit in clinical trials, making 225 mg/day the practical maximum for most patients. 1
- More severely depressed inpatients may require higher doses up to the 375 mg/day maximum, with historical data showing inpatients responding to mean doses of 350 mg/day. 1
Dose Escalation Strategy
- Start at 37.5 mg once or twice daily, then increase by 75 mg increments weekly as tolerated. 2
- The target therapeutic range is 150-225 mg/day for most indications including depression and neuropathic pain. 2, 3
- When increasing doses, increments of up to 75 mg/day should be made at intervals of no less than 4 days. 1
Critical Safety Monitoring at Higher Doses
- Blood pressure monitoring becomes mandatory at doses exceeding 150 mg/day due to dose-dependent hypertension risk. 2, 3
- The incidence of sustained blood pressure elevation increases significantly with dose: 3-5% at ≤200 mg/day, 7% at 201-300 mg/day, and 13% at >300 mg/day (versus 2% with placebo). 4
- Venlafaxine should be prescribed with caution in patients with pre-existing cardiac disease, particularly at higher doses. 2
Tolerability Considerations
- Higher doses (≥375 mg/day) are tolerated but associated with increased frequency and severity of side effects including constipation, sweating, hypertension, agitation, and urinary frequency. 5, 6
- Nausea is the most common dose-dependent side effect and the leading cause of discontinuation, though it typically resolves within 1-3 weeks. 2, 4
- Despite increased side effects at higher doses, discontinuation rates remain comparable to standard dosing in clinical practice. 5
Special Population Adjustments
- Hepatic impairment (mild to moderate): Reduce total daily dose by 50%. 1
- Renal impairment (GFR 10-70 mL/min): Reduce total daily dose by 25%. 1
- Hemodialysis patients: Reduce total daily dose by 50%. 1
- Elderly patients require no dose adjustment based on age alone, though extra caution is warranted when increasing doses. 1