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

Maximum Dose for Effexor (Venlafaxine)

The maximum recommended daily dose of venlafaxine is 375 mg/day in divided doses, as specified by the FDA label, though certain severely depressed inpatients may require and tolerate this maximum dose. 1

Standard Dosing Framework

Outpatient Depression

• The FDA-approved maximum is 375 mg/day administered in two or three divided doses with food 1
• For moderately depressed outpatients, there is no evidence of additional benefit beyond 225 mg/day 1
• Start at 75 mg/day and increase in increments of up to 75 mg at intervals of no less than 4 days 1

Severe or Treatment-Resistant Depression

• More severely depressed inpatients responded to a mean dose of 350 mg/day, indicating that higher doses up to the 375 mg/day maximum may be appropriate in this population 1
• Research demonstrates tolerability of venlafaxine at doses ranging from 375-600 mg/day in treatment-resistant depression, though these exceed FDA recommendations 2
• In a Canadian multicenter trial of treatment-resistant depression, the mean effective dose was 260 mg/day with a maximum of 375 mg/day 3

Anxiety Disorders

• The therapeutic target for anxiety is 150-225 mg/day, which is lower than the depression maximum 4
• If less than 30% symptom reduction occurs after an adequate trial at 225 mg/day, switch to an alternative medication rather than escalating further 4

Critical Safety Monitoring at Higher Doses

Cardiovascular Surveillance

• Blood pressure monitoring is mandatory because venlafaxine causes dose-dependent blood pressure increases, particularly at doses ≥225 mg/day 4, 5
• Check blood pressure and pulse at baseline and throughout treatment 4
• Cardiac conduction abnormalities have been reported in a small number of patients, requiring caution in those with cardiac disease 5

Dose-Specific Adverse Effects

• Higher doses (≥375 mg/day) are associated with increased frequency and severity of side effects including fatigue, concentration difficulties, sleepiness, and memory problems, though discontinuation rates remain low 2
• Nausea is most common during the first 2 weeks and decreases thereafter 6

Special Population Adjustments

Hepatic Impairment

• Reduce total daily dose by 50% in patients with mild to moderate hepatic impairment 1
• Individual variability may require reductions greater than 50% 1

Renal Impairment

• Reduce total daily dose by 25% in mild to moderate renal impairment (GFR 10-70 mL/min) 1
• Reduce total daily dose by 50% in patients undergoing hemodialysis 1

Elderly Patients

• Start at approximately 50% of the standard adult dose due to increased risk of adverse drug reactions 4
• No specific maximum dose adjustment is required based on age alone, but exercise extra caution when increasing doses 1

Common Pitfall to Avoid

• Never discontinue venlafaxine abruptly at any dose—taper over a minimum of 10-14 days to prevent withdrawal syndrome characterized by dizziness, nausea, headache, irritability, and anxiety 4, 5, 1