How should venlafaxine be dosed and titrated in adults, including adjustments for patients ≥65 years, hepatic impairment, renal impairment, and what monitoring and tapering are required?

Venlafaxine Dosing and Titration in Adults

Standard Adult Dosing

Start venlafaxine at 75 mg/day divided into two or three doses with food, then increase to 150 mg/day if needed, with further escalation up to 225 mg/day for most outpatients. 1

• The initial dose of 75 mg/day should be administered in divided doses (two or three times daily) with meals to improve tolerability 1
• Dose increases of up to 75 mg/day can be made at intervals of no less than 4 days 1
• For moderately depressed outpatients, doses above 225 mg/day showed no additional benefit 1
• More severely depressed inpatients may respond to higher doses, with a mean effective dose of 350 mg/day and a maximum of 375 mg/day in three divided doses 1
• Allow 2–4 weeks for patients to reach the efficacious dose range of 150–225 mg/day before assessing response, with a total trial duration of 4–6 weeks to determine effectiveness 2

Dosing in Patients ≥65 Years

No dose reduction is required based on age alone in elderly patients, but use slower titration and exercise extra caution when increasing doses. 1

• The same starting dose (75 mg/day) and maximum dose (225 mg/day for outpatients) apply to elderly patients when age is the only consideration 1
• Employ slower titration schedules in geriatric patients to reduce the risk of adverse effects 2
• When individualizing dosage in the elderly, take extra care during dose escalation 1
• Venlafaxine has been shown to be comparably effective and well tolerated in both younger and older populations, with pooled analysis of over 350 elderly patients demonstrating similar efficacy 3, 4

Hepatic Impairment Adjustments

Reduce the total daily dose by 50% in patients with mild to moderate hepatic impairment or cirrhosis. 1

• Patients with hepatic cirrhosis and mild to moderate hepatic impairment show decreased clearance and increased elimination half-life for both venlafaxine and its active metabolite (ODV) 1
• Because of substantial individual variability in clearance among patients with cirrhosis, some patients may require dose reductions exceeding 50% 1
• Individualization of dosing is desirable in hepatic impairment, with careful monitoring for adverse reactions 1

Renal Impairment Adjustments

Reduce the total daily dose by 25% in patients with mild to moderate renal impairment (GFR 10–70 mL/min) and by 50% in patients undergoing hemodialysis. 1

• Renal impairment causes decreased clearance of venlafaxine and increased elimination half-life for both venlafaxine and ODV 1
• Substantial individual variability exists in clearance among patients with renal impairment, making individualization of dosing desirable 1
• Venlafaxine dosage must be lowered in elderly patients with renal impairment 3

Cardiovascular Monitoring

Measure baseline blood pressure and monitor throughout dose titration, as venlafaxine may cause dose-related increases in supine diastolic blood pressure, especially above 150 mg/day. 2, 3

• Use venlafaxine with caution in individuals with pre-existing cardiac disease due to potential cardiac conduction abnormalities 2
• Venlafaxine may be associated with some increase in supine diastolic blood pressure, particularly at dosages above 150 mg/day 3

Adverse Effect Management

Nausea is the most common adverse effect and typically resolves within 1–3 weeks of continued therapy. 2

• The most frequently reported adverse events include headache, insomnia, nausea, constipation, diaphoresis, and xerostomia 5
• Only 8% of patients discontinued treatment due to adverse events in treatment-resistant depression trials 5
• Transient nausea and headaches are common but generally well tolerated 6

Discontinuation and Tapering

Never discontinue venlafaxine abruptly; always use a gradual dose reduction to avoid withdrawal syndrome. 2, 1

• Symptoms associated with discontinuation of venlafaxine have been reported and require monitoring 1
• If intolerable symptoms occur following dose reduction or discontinuation, resume the previously prescribed dose and then decrease more gradually 1
• A gradual taper is required when discontinuing therapy to minimize withdrawal symptoms 2

MAOI Interactions

Allow at least 14 days between discontinuing an MAOI and starting venlafaxine, and at least 7 days after stopping venlafaxine before starting an MAOI. 1

• Do not start venlafaxine in patients being treated with linezolid or intravenous methylene blue due to increased risk of serotonin syndrome 1

Maintenance Treatment

Continue venlafaxine for several months or longer beyond the acute episode response, with periodic reassessment to determine ongoing need and appropriate dose. 1

• Acute episodes of major depressive disorder require sustained pharmacological therapy beyond response to the acute episode 1
• Longer-term efficacy has been demonstrated in maintenance trials lasting 26–52 weeks 1
• Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose 1

Common Pitfalls to Avoid

• Do not increase doses more rapidly than every 4 days, as this increases the risk of adverse effects without improving efficacy 1
• Do not exceed 225 mg/day in outpatients unless dealing with severely depressed inpatients who may benefit from higher doses 1
• Do not forget to adjust doses in hepatic or renal impairment, as failure to do so significantly increases toxicity risk 1
• Do not abruptly discontinue venlafaxine, as this causes withdrawal symptoms that can be severe 2, 1