Maximum Dose of Effexor (Venlafaxine)
The maximum recommended dose of venlafaxine is 375 mg/day, administered in divided doses (typically three times daily), as specified by the FDA labeling. 1
Standard Dosing Framework
The FDA-approved dosing regimen follows this structure:
- Starting dose: 75 mg/day in two or three divided doses with food 1
- Target therapeutic range: 150-225 mg/day for most patients 1
- Dose escalation: Increase by up to 75 mg/day at intervals of no less than 4 days 1
- Maximum dose: 375 mg/day, generally administered in three divided doses 1
Clinical Context for Maximum Dosing
Higher doses (up to 375 mg/day) are specifically indicated for more severely depressed patients, particularly inpatients. 1 The FDA label explicitly notes that outpatients with moderate depression showed no additional benefit beyond 225 mg/day, but more severely depressed inpatients responded to a mean dose of 350 mg/day. 1
Research confirms that venlafaxine has been studied and used at doses up to 600 mg/day in treatment-resistant depression, though this exceeds FDA-approved maximum dosing. 2 However, the official maximum remains 375 mg/day per regulatory guidance. 1, 3, 4, 5
Critical Safety Monitoring at Higher Doses
Blood pressure monitoring becomes essential at doses above 225 mg/day due to dose-dependent hypertension risk:
- <200 mg/day: 3-5% incidence of BP elevation 4
- 201-300 mg/day: 7% incidence 4
300 mg/day: 13% incidence 4
- In older adults (≥60 years), 9.8% developed elevated BP at doses ≥225 mg/day 6
Orthostatic hypotension is also a significant concern, particularly in older adults, with 22.4% experiencing new-onset orthostatic hypotension at doses ≥225 mg/day, which significantly increases fall risk. 6
Special Population Dose Adjustments
When prescribing at any dose level, mandatory reductions apply:
- 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 alternative medication rather than dose reduction due to significantly reduced clearance 7
Common Pitfall to Avoid
Do not abruptly discontinue venlafaxine at any dose. Taper over 10-14 days minimum to prevent withdrawal syndrome, which can occur even at lower doses. 7