What is the recommended starting dose of Venlafaxine (Effexor) ER?

Venlafaxine ER Starting Dose

The recommended starting dose for venlafaxine ER is 37.5 mg once or twice daily, with a gradual increase by 75 mg each week to an efficacious dosage of 150-225 mg/day. 1, 2

Dosing Guidelines for Venlafaxine ER

• The FDA-approved starting dose for venlafaxine tablets is 75 mg/day, administered in two or three divided doses, taken with food 2
• For better tolerability, especially in patients who may be sensitive to side effects, starting at 37.5 mg once or twice daily is recommended 1
• Titration should occur gradually, with increases of 75 mg each week as tolerated 1
• The target therapeutic dosage range is 150-225 mg/day, which typically takes 2-4 weeks to reach 1
• Maximum dosage is 225 mg/day for outpatients, though more severely depressed inpatients may respond to higher doses up to 375 mg/day 2

Special Populations and Dosage Adjustments

• Hepatic impairment: Reduce total daily dose by 50% in patients with mild to moderate hepatic impairment; further individualization may be necessary in cirrhosis 2
• Renal impairment: Reduce total daily dose by 25% in mild to moderate renal impairment (GFR 10-70 mL/min) and by 50% in patients undergoing hemodialysis 2
• Elderly patients: No specific dose adjustment is recommended based on age alone, but extra caution should be exercised when increasing the dose 2

Efficacy and Mechanism of Action

• Venlafaxine is a serotonin-norepinephrine reuptake inhibitor (SNRI) with dual action that is dose-dependent 3
• At lower doses, it primarily inhibits serotonin reuptake, while norepinephrine reuptake inhibition becomes clinically relevant at higher doses 3
• Venlafaxine has shown efficacy in painful diabetic peripheral neuropathy and painful polyneuropathies, though not in postherpetic neuralgia 1
• In severe depression, higher doses (>300 mg/day) may provide additional benefits for extremely ill patients 3

Side Effects and Monitoring

• Common side effects include nausea, dizziness, constipation, sweating, nervousness, and abnormal ejaculation 4
• Nausea is the most common adverse effect but typically resolves within 1-3 weeks of starting therapy 4
• Cardiac conduction abnormalities and blood pressure increases can occur, particularly at higher doses; venlafaxine should be prescribed with caution in patients with cardiac disease 1
• Blood pressure monitoring is recommended, as dose-dependent elevations occur in 3-13% of patients depending on dosage 4
• Venlafaxine should be tapered when discontinuing treatment to prevent withdrawal syndrome 1

Important Clinical Considerations

• Venlafaxine is available in both short-acting and long-acting (ER) preparations 1
• An adequate trial of venlafaxine for neuropathic pain requires 4-6 weeks 1
• For depression, early responses are often seen at higher dosages, with some studies showing clinical superiority over placebo as early as Week 1 4
• Venlafaxine may be more effective than switching to another SSRI in patients with severe depression who have failed initial SSRI therapy 5

By starting at a lower dose (37.5 mg daily or twice daily) and gradually titrating upward, clinicians can minimize side effects while working toward the therapeutic dosage range of 150-225 mg/day for most patients.