What is the recommended dosing for Effexor (venlafaxine) in adults with depression or anxiety, particularly those with a history of seizures, bleeding disorders, or impaired renal or hepatic function?

Effexor (Venlafaxine) Dosing

Standard Dosing for Depression and Anxiety

The recommended starting dose for venlafaxine is 75 mg/day in two or three divided doses with food, with dose increases of up to 75 mg/day at intervals of no less than 4 days, up to a maximum of 375 mg/day. 1

Initial Dosing Algorithm

• Start at 75 mg/day divided into 2-3 doses with food 1
• Increase to 150 mg/day if needed based on tolerability and clinical response 1
• Further titrate to 225 mg/day for most outpatients with moderate depression 1
• Consider doses up to 375 mg/day (generally in three divided doses) for severely depressed or treatment-resistant patients, particularly inpatients 1, 2

Evidence for Dose-Response Relationship

• Doses of 75-225 mg/day demonstrate clear dose-related efficacy, with higher doses showing faster onset of clinical improvement (as early as 1-2 weeks at 150-200 mg/day) 3
• No evidence of additional benefit beyond 225 mg/day in moderately depressed outpatients, though severely depressed inpatients responded to mean doses of 350 mg/day 1
• Anxiety symptoms in depression respond to 75-225 mg/day, with significant improvements noted as early as week 1 at higher doses 4

Special Population Dosing Adjustments

Renal Impairment

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

• Reduce total daily dose by 50% in patients undergoing hemodialysis 1
• Venlafaxine elimination half-life is prolonged by approximately 180% in dialysis patients, and clearance is reduced by 57% 1
• Individual variability is substantial, so further dose reduction may be necessary 1

Hepatic Impairment

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

• Venlafaxine clearance decreases by approximately 50% in cirrhotic patients, with elimination half-life prolonged by 30% 1
• Patients with severe cirrhosis (Child-Pugh B or C) may require dose reductions exceeding 50%, as some patients showed 90% reduction in clearance 1
• Oral bioavailability increases 2-3 fold in hepatically impaired patients 1
• Individual variability necessitates careful dose individualization 1

Elderly Patients

No routine dose adjustment is required based on age alone, though caution and slower titration are advised. 1

• Pharmacokinetic analysis of 404 patients showed no age-related differences in drug exposure 1
• Extra care should be taken when increasing doses in elderly patients 1

Patients with History of Seizures

Venlafaxine should be used with caution in patients with seizure history, though the FDA label does not specify dose adjustments for this population. 1

• Start at the lower end of the dosing range (75 mg/day) and titrate slowly
• Monitor closely for any seizure activity during dose escalation

Patients with Bleeding Disorders

Exercise caution when prescribing venlafaxine to patients with bleeding disorders or those on anticoagulants, as SNRIs can affect platelet function. 1

• No specific dose adjustment is recommended, but close monitoring for bleeding is essential
• Consider starting at 75 mg/day with careful titration

Discontinuation Protocol

Gradual dose reduction is mandatory when discontinuing venlafaxine to minimize withdrawal symptoms. 1

• Never discontinue abruptly - taper the dose gradually over time 1
• If intolerable symptoms occur during taper, resume the previous dose and decrease more slowly 1
• Allow at least 7 days after stopping venlafaxine before starting an MAOI 1

Common Pitfalls to Avoid

• Underdosing: Many patients require 150-225 mg/day for optimal response; don't stop at 75 mg/day if response is inadequate 3
• Too-rapid titration: Increase by no more than 75 mg/day at intervals of at least 4 days to minimize side effects 1
• Ignoring renal/hepatic function: Failure to adjust doses in impaired patients leads to excessive drug exposure and increased adverse effects 1
• Abrupt discontinuation: Always taper gradually to prevent withdrawal syndrome 1
• Inadequate trial duration: Allow 4-6 weeks at therapeutic doses before concluding treatment failure 3

Monitoring Requirements

• Blood pressure monitoring is essential, particularly at doses above 225 mg/day, as dose-dependent increases can occur 2, 5
• Monitor for common adverse effects including nausea (most common), dizziness, somnolence, insomnia, dry mouth, and sweating 3, 4, 6
• Most adverse effects occur early in treatment and decrease with time 6