Venlafaxine Dosing Regimen
Start venlafaxine at 75 mg/day divided into 2-3 doses with food, increase by up to 75 mg/day at intervals of no less than 4 days based on tolerability and clinical response, with a typical effective range of 150-225 mg/day for outpatients and up to 375 mg/day maximum for severely depressed patients. 1
Initial Dosing
- Begin with 75 mg/day administered in two or three divided doses, taken with food 1
- This starting dose is sufficient for the majority of patients and minimizes initial side effects 2
- The minimum effective dose is 75 mg/day 3
Dose Titration
- Increase the dose to 150 mg/day if needed based on tolerability and clinical effect 1
- Further increases up to 225 mg/day can be made for additional benefit 1
- When increasing, use increments of up to 75 mg/day at intervals of no less than 4 days 1
- This gradual titration approach (2-4 weeks to reach efficacious dosing of 150-225 mg/day) reduces adverse effects 4
Maximum Dosing
- For outpatients with moderate depression, doses above 225 mg/day show no additional evidence of benefit 1
- More severely depressed inpatients may respond to higher doses, with a mean effective dose of 350 mg/day 1
- The absolute maximum dose is 375 mg/day, generally divided into three doses 1
- Higher doses (up to 600 mg/day) have been studied and tolerated, though with increased side effect severity, particularly for fatigue, concentration difficulties, and sedation 5
Dosing by Clinical Setting
- Inpatient settings typically require higher doses than outpatient settings 2
- Severity of illness and previous antidepressant treatment history predict need for higher dosing 2
- In extremely ill patients, very high dosages are associated with better response rates 2
Special Population Adjustments
Hepatic Impairment
- Reduce total daily dose by 50% in patients with mild to moderate hepatic impairment 1
- Venlafaxine clearance decreases by approximately 50% and elimination half-life increases by 30% in cirrhotic patients 1
- Patients with severe cirrhosis may require dose reductions exceeding 50% 1
Renal Impairment
- Reduce total daily dose by 25% in patients with mild to moderate renal impairment (GFR 10-70 mL/min) 1
- Reduce total daily dose by 50% in patients undergoing hemodialysis 1
- Elimination half-life is prolonged by approximately 50% in renally impaired patients 1
Elderly Patients
- No routine dose adjustment is required based solely on age 1
- Exercise caution and use extra care when increasing doses in elderly patients 1
Important Safety Considerations
Cardiovascular Monitoring
- Monitor blood pressure, particularly at higher doses, as venlafaxine can cause dose-dependent blood pressure increases 4
- Prescribe with caution in patients with cardiac disease due to reports of cardiac conduction abnormalities 4
- Approximately 10% of patients on average doses of 342 mg/day may experience mildly elevated blood pressure 5
Discontinuation
- Taper venlafaxine when discontinuing treatment to avoid withdrawal syndrome 4
- Discontinue over 10-14 days to limit withdrawal symptoms 4
Pregnancy Considerations
- Carefully weigh risks versus benefits when treating pregnant women during the third trimester, as neonates exposed to venlafaxine late in pregnancy may develop complications requiring prolonged hospitalization 1
Clinical Response Timeline
- Significant improvement from placebo can be observed as early as 4 days to 1 week at doses of 375 mg/day 3
- An adequate trial requires 4-6 weeks, including time for titration 4
- Response rates improve with increased dosage in outpatients, particularly among severely ill patients 2