Maximum Dose of Venlafaxine
The maximum daily dose of venlafaxine is 375 mg/day for adult patients with major depression, administered in divided doses, as specified by the FDA label. 1
FDA-Approved Maximum Dosing
- The FDA-approved maximum dose is 375 mg/day, generally administered in three divided doses for the immediate-release formulation. 1
- For outpatient settings with moderately depressed patients, there was no evidence of usefulness beyond 225 mg/day. 1
- More severely depressed inpatients responded to a mean dose of 350 mg/day, and certain severely depressed patients may require up to the maximum of 375 mg/day. 1
Standard Therapeutic Dosing Range
- The target therapeutic dose is 150-225 mg/day, which represents the efficacious range for most indications including depression and neuropathic pain. 2
- The recommended starting dose is 75 mg/day (immediate-release) or 37.5 mg once or twice daily (extended-release), with dose increases of up to 75 mg/day at intervals of no less than 4 days. 1, 2
- For routine outpatient depression, the maximum dose is 225 mg/day. 2
Critical Safety Monitoring at Higher Doses
- Blood pressure monitoring becomes essential at doses exceeding 150 mg/day due to dose-dependent hypertension risk. 2, 3
- Cardiac conduction abnormalities have been reported in a small number of patients, requiring caution in those with cardiac disease. 3
- Common side effects include nausea (most common reason for discontinuation), dry mouth, decreased appetite, constipation, dizziness, somnolence, insomnia, sweating, and sexual dysfunction, occurring in a dose-dependent manner. 2
Evidence for Higher Doses
- Research demonstrates that venlafaxine is tolerated at doses up to 600 mg/day in treatment-resistant depression, though with increased frequency and severity of side effects. 4
- Higher doses (≥375 mg/day) were associated with fewer hospital days and outpatient visits compared to standard doses in patients with major depression. 5
- However, the FDA label remains the authoritative source, capping the maximum at 375 mg/day for general clinical practice. 1
Dose Adjustments for Special Populations
- 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
- CYP2D6 poor metabolizers: Consider switching to an alternative antidepressant rather than dose reduction, as they have significantly reduced clearance and higher risk for adverse effects. 3
Discontinuation Protocol
- Venlafaxine must always be tapered gradually and never discontinued abruptly to avoid withdrawal syndrome. 2, 3
- Taper over 10-14 days minimum, though slower tapers (10% reductions per week or per month) may be necessary for some patients. 2
- Withdrawal symptoms are well-documented and can be severe; some patients may require tapering over several months. 2