Recommended Dosage and Treatment Protocol for Venlafaxine (Effexor)
The recommended starting dose for venlafaxine is 75 mg/day administered in two or three divided doses, taken with food, with gradual titration up to 225 mg/day based on clinical response and tolerability. 1
Initial Dosing and Titration
- Starting dose: 75 mg/day in two or three divided doses with food 1
- Titration: Increase by up to 75 mg/day at intervals of no less than 4 days 1
- Target dose range:
Dosing Schedule
- Immediate-release (IR): Administered in 2-3 divided doses daily with food
- Extended-release (XR): Can be administered once daily, which may improve adherence 3
Special Population Considerations
Renal Impairment
- Mild to moderate impairment (GFR 10-70 mL/min): Reduce total daily dose by 25% 1
- Hemodialysis patients: Reduce total daily dose by 50% 1
Hepatic Impairment
- Mild to moderate impairment: Reduce total daily dose by 50% 1
- Cirrhosis: May require more than 50% reduction; individualize dosing 1
Elderly Patients
- No specific dose adjustment based on age alone, but use caution when increasing dose 1
- Consider starting at lower doses and titrating more slowly 2
Duration of Treatment
- Acute phase: 4-8 weeks to assess initial response
- Continuation phase: Continue for 4-12 months after response to a first episode of major depression 2
- Maintenance phase: For recurrent depression, longer-term treatment may be necessary to prevent relapse 2
Discontinuation Protocol
- Never discontinue venlafaxine abruptly due to risk of withdrawal symptoms 1
- Implement a gradual dose reduction:
- Decrease by 75 mg every 4-7 days
- If withdrawal symptoms occur, resume previous dose and taper more slowly 1
- Consider even more gradual tapering for patients on long-term treatment
Monitoring
- Initial period: Assess every 1-2 weeks for efficacy and side effects
- Maintenance: Evaluate every 1-3 months
- Monitor for:
- Blood pressure changes (dose-dependent increases can occur)
- Suicidal ideation, especially in young adults
- Serotonin syndrome if combined with other serotonergic medications
Common Side Effects and Management
- Gastrointestinal: Nausea, dry mouth
- Neurological: Dizziness, somnolence, insomnia
- Urogenital: Abnormal ejaculation
- Other: Sweating, headache
Drug Interactions
- MAOIs: Allow at least 14 days between stopping an MAOI and starting venlafaxine, and at least 7 days between stopping venlafaxine and starting an MAOI 1
- Linezolid/Methylene blue: Avoid concurrent use due to risk of serotonin syndrome 1
- Other serotonergic drugs: Use with caution due to increased risk of serotonin syndrome
Clinical Pearls
- Venlafaxine is a dual serotonin and norepinephrine reuptake inhibitor, with more potent effects on serotonin reuptake at lower doses and norepinephrine effects emerging at higher doses 4
- For patients with severe depression (HAM-D score >31), venlafaxine may be more effective than SSRIs 5
- The antidepressant effect may begin earlier than the full therapeutic effect, which typically takes 4-6 weeks 3
- For neuropathic pain, venlafaxine can be used as a coanalgesic in combination with an opioid 2
Treatment Resistance
For patients with partial response to venlafaxine alone:
- Consider dose optimization to maximum tolerated dose before changing strategies
- In treatment-resistant cases, some evidence supports combining venlafaxine with an SSRI, though this should be done with caution and monitoring for serotonin syndrome 6