What is the recommended dosing for Effexor XR (venlafaxine) in adults?

Effexor XR Dosing

Start with 75 mg once daily and titrate to 150-225 mg/day, which is the therapeutic range that typically requires 2-4 weeks to achieve full efficacy. 1, 2

Initial Dosing

• Begin with 75 mg/day administered with food 2
• For the immediate-release formulation, divide into 2-3 doses per day; the extended-release (XR) formulation allows once-daily dosing 1, 2
• The XR formulation improves tolerability and is preferred for convenience 1

Dose Titration

• Increase in increments of up to 75 mg/day at intervals of no less than 4 days if tolerability allows and clinical response is inadequate 2
• The target therapeutic dose is 150-225 mg/day, which is effective for most outpatients with moderate depression 1, 2
• More severely depressed patients (particularly inpatients) may require up to 375 mg/day in divided doses, with a mean effective dose around 350 mg/day 2
• While the FDA label lists 375 mg/day as the maximum, clinical studies have demonstrated tolerability up to 600 mg/day in treatment-resistant cases, though side effects increase in frequency and severity at these higher doses 3

Special Population Adjustments

Hepatic Impairment

• Reduce total daily dose by 50% in patients with mild to moderate hepatic impairment or cirrhosis 2
• More severe cirrhosis may require dose reductions exceeding 50%; individualize based on clinical response 2

Renal Impairment

• Reduce total daily dose by 25% in patients with mild to moderate renal impairment (GFR 10-70 mL/min) 2
• Reduce total daily dose by 50% in patients undergoing hemodialysis 2

Elderly Patients

• No specific dose adjustment required based on age alone 1, 2
• Use slower titration and exercise caution when increasing doses in elderly patients 1

Neuropathic Pain Dosing (Off-Label)

• Start with 37.5 mg once or twice daily 1
• Titrate by increasing 75 mg each week 1
• Target therapeutic dose: 150-225 mg/day (maximum 225 mg/day) 1
• Allow 4-6 weeks at therapeutic dose for an adequate trial 1

Critical Monitoring Requirements

• Monitor blood pressure, particularly at doses >200 mg/day, as dose-dependent increases can occur 1
• Exercise caution in patients with cardiac disease due to rare reports of cardiac conduction abnormalities 1
• Blood pressure monitoring is especially important as approximately 10% of patients on average doses of 342 mg/day may develop mildly elevated blood pressure 3

Discontinuation

• Always taper when discontinuing—never stop abruptly 1
• Withdrawal syndrome is well-described with venlafaxine and can be severe 1

Common Pitfalls to Avoid

• Nausea is the most common adverse effect, with highest incidence during the first 2 weeks; reassure patients that this typically improves 4
• Other frequent side effects include dizziness, somnolence, insomnia, dry mouth, sweating, and sexual dysfunction (particularly abnormal ejaculation) 5
• Do not assume lack of response at lower doses—venlafaxine demonstrates superior efficacy at 150 mg/day compared to 75 mg/day in patients who don't respond early to treatment 6
• The extended-release formulation is significantly more effective than immediate-release at equivalent doses (75-150 mg/day) 4