Effexor XR (Venlafaxine Extended-Release) Dosing
Start venlafaxine XR at 37.5 mg once or twice daily, increase by 75 mg weekly to reach the target therapeutic dose of 150-225 mg/day, with a maximum of 375 mg/day for severe depression if needed. 1, 2, 3
Initial Dosing
- Begin with 37.5 mg once or twice daily as the starting dose 1, 2
- For the immediate-release formulation, the FDA-approved starting dose is 75 mg/day divided into 2-3 doses with food, but the extended-release formulation allows for lower initial dosing 3
Titration Schedule
- Increase the dose by 75 mg increments weekly as tolerated 1, 2
- The FDA label specifies that dose increases should occur at intervals of no less than 4 days when using 75 mg increments 3
- The next step after initial dosing is typically 150 mg/day, which represents the lower end of the therapeutic range 1
Target Therapeutic Dose
- The target dose is 150-225 mg/day for most indications including major depression and neuropathic pain 1, 2
- This dose range demonstrates significantly better efficacy than lower doses in clinical trials, with 75 mg/day being the minimum effective dose 1
- Clinical response rates at 150 mg/day were superior to both lower doses and comparator antidepressants in controlled trials 4, 5
Maximum Dosing
- The maximum dose is 225 mg/day for routine outpatient depression 1
- For more severely depressed patients, particularly inpatients, doses up to 375 mg/day may be used in three divided doses 3, 6
- Outpatient studies showed no additional benefit beyond 225 mg/day for moderately depressed patients, but inpatients responded to mean doses of 350 mg/day 3
Critical Monitoring Requirements
- Monitor blood pressure at doses exceeding 150 mg/day due to dose-dependent hypertension risk 1, 2
- The incidence of sustained blood pressure elevation increases with dose: 3-5% at ≤200 mg/day, 7% at 201-300 mg/day, and 13% at >300 mg/day versus 2% with placebo 6
- Exercise caution in patients with pre-existing cardiac disease 1
Special Population Dosing
Hepatic Impairment
- Reduce total daily dose by 50% in patients with mild to moderate hepatic impairment 3
- Individual variability may require even greater dose reductions; individualization is necessary 3
Renal Impairment
- Reduce total daily dose by 25% in patients with mild to moderate renal impairment (GFR 10-70 mL/min) 3
- Reduce total daily dose by 50% in patients undergoing hemodialysis 3
Elderly Patients
- No specific dose adjustment required based on age alone, but exercise caution when increasing doses 3
Discontinuation Protocol
- Always taper gradually—never stop abruptly to avoid withdrawal syndrome 1, 2
- Withdrawal syndrome is well-documented and can be severe with venlafaxine 1, 2
- Reduce dose by approximately 50% per week over at least 2 weeks as a general approach 2
- If intolerable symptoms occur during taper, resume the previous dose and decrease more gradually 3
Common Adverse Effects
- Nausea is the most common side effect and occurs in a dose-dependent manner, but typically resolves within 1-3 weeks 1, 6
- Other frequent adverse effects include dry mouth, decreased appetite, constipation, dizziness, somnolence, insomnia, sweating, and sexual dysfunction 1, 6
- Nausea was the most common reason for discontinuation (6% of patients) in clinical trials 6
MAOI Interactions
- Allow at least 14 days after stopping an MAOI before starting venlafaxine 3
- Allow at least 7 days after stopping venlafaxine before starting an MAOI 3
- Do not use venlafaxine with linezolid or intravenous methylene blue due to serotonin syndrome risk 3
Clinical Efficacy Considerations
- Therapeutic response may be evident as early as week 2 of treatment 4
- Some studies suggest clinical superiority over placebo by week 1, with inpatient studies showing benefit as early as day 4 at higher doses 6
- Higher doses (150 mg/day) demonstrated superiority over fluoxetine in patients who did not respond early to treatment 5