What is the maximum recommended dose of venlafaxine (Effexor) per day?

Maximum Recommended Dose of Venlafaxine (Effexor)

The maximum recommended dose of venlafaxine is 375 mg/day, though severely depressed inpatients may respond to this maximum dose while most outpatients typically do not require more than 225 mg/day. 1

Dosing Guidelines

Initial Dosing and Titration

• Starting dose: 75 mg/day, administered in two or three divided doses, taken with food 1
• Titration: Increase by up to 75 mg/day at intervals of no less than 4 days 1
• Standard effective dosing:
  • For most outpatients: 75-225 mg/day 1
  • For severely depressed inpatients: Mean effective dose of 350 mg/day, up to maximum of 375 mg/day 1

Dose Considerations by Patient Population

Patients with Hepatic Impairment

• Reduce total daily dose by 50% in patients with mild to moderate hepatic impairment 1
• Further individualization may be necessary for patients with cirrhosis due to significant variability in clearance 1

Patients with 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

Elderly Patients

• No specific dose adjustment recommended based on age alone 1
• Exercise caution when increasing the dose in elderly patients 1

Clinical Applications

For Depression

• Effective dose range: 75-375 mg/day 2
• Minimum effective dose: 75 mg/day 2
• Positive dose-response effect demonstrated with doses up to 375 mg/day 2

For Neuropathic Pain

• Recommended dose range: 150-225 mg/day 3
• Duration of adequate trial: 4-6 weeks 3

For Painful Diabetic Peripheral Neuropathy

• Effective dose range: 150-225 mg/day 3
• Note: Cardiovascular adverse events may limit use in diabetic patients 3

Safety Considerations

Cardiovascular Effects

• Monitor for cardiac conduction abnormalities, especially at higher doses 3
• Blood pressure increases can occur; use with caution in patients with cardiac disease 3
• Risk of sudden cardiac death is associated with TCA doses >100 mg/day, but venlafaxine has a better cardiac safety profile than TCAs 3, 4

Discontinuation

• Taper when discontinuing treatment to prevent withdrawal syndrome 3
• Typical tapering period: 10-14 days to limit withdrawal symptoms 3

Tolerability at Higher Doses

• Higher doses (375-600 mg/day) have been used in treatment-resistant depression 5
• At doses above 375 mg/day, patients may experience increased severity of side effects including fatigue, concentration difficulties, sleepiness/sedation, and memory issues 5
• Despite increased side effects at higher doses, discontinuation rates remain relatively low 5

Common Adverse Effects

• Digestive: Nausea, dry mouth
• Nervous system: Dizziness, somnolence, insomnia
• Urogenital: Abnormal ejaculation
• Other: Sweating 6

Key Takeaways

• The FDA-approved maximum dose is 375 mg/day 1
• Most outpatients respond adequately to doses of 225 mg/day or less 1
• Higher doses may be necessary for severely depressed inpatients 1
• Dose adjustments are required for patients with hepatic or renal impairment 1
• Monitor for blood pressure changes, especially at higher doses 3

Remember that while higher doses may be more effective for some patients, they also carry increased risk of side effects. Always balance efficacy against tolerability when determining the optimal dose for individual patients.