Venlafaxine (Effexor) Titration Schedule
Start venlafaxine at 75 mg/day divided into 2-3 doses with food, then increase by 75 mg increments at intervals of no less than 4 days, targeting 150-225 mg/day for most patients. 1
Standard Titration Protocol
Initial Dosing
- Begin at 75 mg/day administered in two or three divided doses, taken with food 1
- Alternative starting approach: 37.5 mg twice daily for patients requiring slower titration 2
Dose Escalation
- Increase by 75 mg/day at intervals of no less than 4 days based on tolerability and clinical response 1
- First target: 150 mg/day 1
- If additional effect needed: titrate to 225 mg/day 1
- Maximum dose: 375 mg/day (generally in three divided doses) 1
Time to Therapeutic Effect
- 2-4 weeks typically required to reach efficacious dosing for most indications 3, 4
- Some patients show early response by Week 1 at higher doses 5
Therapeutic Dosing by Indication
Depression
- Outpatient depression: 75-225 mg/day usually sufficient; no evidence of benefit beyond 225 mg/day in moderately depressed patients 1
- Severe/inpatient depression: Mean effective dose 350 mg/day; may require up to 375 mg/day 1
- Treatment-resistant depression: Mean dose 260 mg/day (range up to 375 mg/day) showed 58% response rate 2
Neuropathic Pain
- Target range: 150-225 mg/day for efficacy 3, 4
- Minimum effective dose: 75 mg/day 4
- Start at 37.5 mg once or twice daily, increase by 75 mg weekly 6
Critical Safety Monitoring During Titration
Blood Pressure Surveillance
- Dose-dependent hypertension risk: 3-5% at ≤200 mg/day, 7% at 201-300 mg/day, 13% at >300 mg/day 5
- Monitor blood pressure regularly, especially when escalating above 225 mg/day 3, 4
Cardiac Considerations
- Use caution in cardiac disease: Cardiac conduction abnormalities reported in small numbers 3, 4
- Venlafaxine should be prescribed cautiously in patients with pre-existing cardiac conditions 3
Common Side Effects During Titration
- Most frequent: Nausea (6% discontinuation rate), somnolence, insomnia, dizziness (each 3% discontinuation) 5
- Nausea typically resolves within 1-3 weeks 5
- Other common effects: constipation, sweating, nervousness, sexual dysfunction 5
Special Population Adjustments
Hepatic Impairment
- Reduce total daily dose by 50% in mild to moderate hepatic impairment 1
- May require >50% reduction in cirrhosis due to individual variability 1
Renal Impairment
- Mild to moderate (GFR 10-70 mL/min): Reduce total daily dose by 25% 1
- Hemodialysis: Reduce total daily dose by 50% 1
Elderly Patients
- No specific dose adjustment required based on age alone 1
- Exercise extra caution when increasing doses 1
Discontinuation Protocol
Tapering Requirements
- Never abruptly discontinue: Withdrawal syndrome well-documented 3, 4
- Taper over 10-14 days minimum to limit withdrawal symptoms 3, 4
- Longer tapers may be needed for higher doses or longer treatment duration
High-Dose Considerations (>375 mg/day)
When to Consider
Tolerability Data
- Doses up to 600 mg/day studied: Tolerable but increased frequency and severity of side effects (fatigue, concentration difficulties, sedation, memory problems) 7
- Discontinuation rates not significantly higher despite increased side effects 7
- Therapeutic plasma concentration: 195-400 ng/mL (venlafaxine plus O-desmethylvenlafaxine) 4, 6
Pharmacogenetic Considerations
CYP2D6 Poor Metabolizers
- Consider alternative medication rather than dose reduction 4
- Significantly reduced clearance increases adverse effect risk 4
- Switching to differently metabolized antidepressant preferred over careful monitoring 4