Venlafaxine ER Dosing
Start venlafaxine ER at 37.5-75 mg once daily, titrate by 75 mg weekly to a target of 150-225 mg/day, with a maximum of 375 mg/day for severe or treatment-resistant depression. 1, 2
Initial Dosing
- Begin with 37.5 mg once or twice daily for extended-release formulations, which allows assessment of tolerability before escalation 1
- The FDA-approved immediate-release formulation starts at 75 mg/day in divided doses with food, but ER formulations permit once-daily dosing 2
- Starting at the lower 37.5 mg dose minimizes early nausea, the most common side effect that typically resolves within 1-3 weeks 3
Titration Schedule
- Increase the dose by 75 mg increments weekly as tolerated 1
- The FDA label specifies intervals of no less than 4 days between dose increases for immediate-release formulations 2
- This gradual titration balances achieving therapeutic effect against tolerability 1, 4
Target Therapeutic Range
- The target dose is 150-225 mg/day for most patients with major depression, which represents the optimal balance of efficacy and tolerability 1, 2
- At 75 mg/day, venlafaxine demonstrates significant superiority over placebo, establishing this as the minimum effective dose 5, 6
- For outpatient depression of moderate severity, doses above 225 mg/day showed no additional benefit in clinical trials 2
Maximum Dosing for Severe Depression
- The maximum dose is 375 mg/day, reserved for severely depressed inpatients or treatment-resistant cases 1, 2
- More severely depressed inpatients in clinical trials responded to a mean dose of 350 mg/day 2
- Higher doses (>300 mg/day) demonstrated earlier onset of antidepressant effect, with significant improvement observed as early as day 4 in inpatient studies 5
- Treatment setting is the strongest predictor of high-dose prescribing, with inpatients receiving substantially higher doses than outpatients 4
Critical Monitoring Requirements
- Monitor blood pressure at doses exceeding 150 mg/day due to dose-dependent hypertension risk 1
- The incidence of sustained blood pressure elevation increases progressively: 3-5% at ≤200 mg/day, 7% at 201-300 mg/day, and 13% at >300 mg/day versus 2% with placebo 3
- This represents a key safety distinction from SSRIs and requires vigilant monitoring at higher doses 1
Special Population Adjustments
- Reduce total daily dose by 50% in patients with mild-to-moderate hepatic impairment due to decreased clearance and prolonged half-life 2
- Reduce total daily dose by 25% in mild-to-moderate renal impairment (GFR 10-70 mL/min) 2
- Reduce total daily dose by 50% in patients on hemodialysis 2
- No routine dose adjustment is needed for elderly patients based on age alone, though extra caution is warranted during titration 2
Discontinuation Protocol
- Always taper venlafaxine gradually—never stop abruptly due to well-documented withdrawal syndrome risk 1, 2
- If intolerable symptoms emerge during dose reduction, resume the previous dose and taper more gradually 2
- The short half-life of venlafaxine makes it particularly prone to discontinuation symptoms compared to longer-acting antidepressants 1
MAOI Interactions
- Allow at least 14 days after stopping an MAOI before starting venlafaxine 2
- Allow at least 7 days after stopping venlafaxine before starting an MAOI 2
- For urgent situations requiring linezolid or IV methylene blue in patients on venlafaxine, stop venlafaxine promptly and monitor for serotonin syndrome for 7 days 2
Clinical Pearls for Dose Optimization
- A stepwise approach is most rational: start at 75 mg/day for the majority of patients, and escalate to upper limits only in cases of non-response before considering treatment failure 4
- Severely ill patients specifically benefit from very high doses (>300 mg/day), with better response rates than at standard doses 4
- The dual serotonin-norepinephrine reuptake inhibition becomes clinically relevant only at higher doses (>150 mg/day), allowing tailored treatment through differential dosing 4