Venlafaxine ER Dosing
Start venlafaxine ER at 37.5-75 mg once daily, then increase by 75 mg weekly to reach the therapeutic target of 150-225 mg/day, which typically takes 2-4 weeks. 1, 2
Initial Dosing
- For the ER formulation: Begin at 37.5 mg once or twice daily for patients who may be sensitive to side effects, or start at 75 mg once daily for standard initiation 1
- For immediate-release tablets: The FDA-approved starting dose is 75 mg/day divided into 2-3 doses with food 2
- The ER formulation allows once-daily dosing, which improves adherence and reduces peak-related nausea compared to immediate-release formulations 3
Titration Schedule
- Increase by 75 mg increments weekly as tolerated 1
- Minimum interval between dose increases: 4 days (per FDA labeling for immediate-release, though weekly increases are more practical for ER) 2
- The gradual weekly titration minimizes side effects, particularly nausea, which is the most common reason for discontinuation 1, 4
Target Therapeutic Dose
- Standard therapeutic range: 150-225 mg/day 1
- This range is effective for most outpatients with moderate depression 2
- Time to reach therapeutic dose: 2-4 weeks with weekly titration 1
Higher Doses for Severe or Refractory Depression
- Maximum dose: 375 mg/day 2, 5
- Severely depressed inpatients may require higher doses (mean effective dose 350 mg/day in one study) 2
- The dual mechanism (serotonin and norepinephrine reuptake inhibition) becomes more pronounced at higher doses, with norepinephrine effects emerging above 150 mg/day 6
- Higher doses (>300 mg/day) are associated with better response in severely ill patients but carry increased risk of dose-dependent blood pressure elevation 6, 4
Special Population Adjustments
- Mild-to-moderate hepatic impairment: Reduce total daily dose by 50% 2
- Mild-to-moderate renal impairment (GFR 10-70 mL/min): Reduce total daily dose by 25% 2
- Hemodialysis patients: Reduce total daily dose by 50% 2
- Elderly patients: No routine dose adjustment needed based on age alone, but use caution when increasing doses 2
Monitoring Requirements
- Blood pressure monitoring is essential, particularly at doses >200 mg/day, where 7-13% of patients may experience dose-dependent hypertension (compared to 3-5% at ≤200 mg/day) 4, 7
- Cardiac conduction should be monitored in patients with pre-existing cardiac disease, though venlafaxine causes fewer conduction abnormalities than tricyclic antidepressants 1, 7
Discontinuation
- Always taper gradually rather than stopping abruptly to prevent withdrawal syndrome 1, 2
- If intolerable symptoms occur during taper, resume the previous dose and decrease more slowly 2
- Allow at least 7 days after stopping venlafaxine before starting an MAOI 2