Venlafaxine Dosing for Depression and Anxiety
Standard Dosing Regimen
Start venlafaxine at 75 mg/day divided into 2-3 doses with food, then increase by 75 mg increments every 4 days or longer based on tolerability, targeting 150-225 mg/day for most patients with depression or anxiety. 1
Initial Dosing
- Starting dose: 75 mg/day in 2-3 divided doses with food 1
- Increase to 150 mg/day if needed for further clinical effect 1
- Maximum standard dose: 225 mg/day for outpatients with moderate depression 1
- Severely depressed patients may require up to 375 mg/day in three divided doses 1
Dose Escalation Timeline
- Increase in increments of up to 75 mg/day at intervals of no less than 4 days 1
- Clinical response may be evident as early as week 2, with significant improvement by week 4 2
- Dose-related improvements are most evident at 150-200 mg/day, with significant effects noted at weeks 1-2 at higher doses 3
Special Population Adjustments
Renal Impairment
- Mild to moderate renal impairment (GFR 10-70 mL/min): Reduce total daily dose by 25% 1
- Hemodialysis patients: Reduce total daily dose by 50% 1
- Individual variability in clearance requires dose individualization in some patients 1
Hepatic Impairment
- Mild to moderate hepatic impairment: Reduce total daily dose by 50% 1
- Patients with cirrhosis may require dose reductions exceeding 50% due to individual variability in clearance 1
Elderly Patients (Age >65)
- No routine dose adjustment required based on age alone 1
- However, start at approximately 50% of the standard adult starting dose (37.5 mg/day) to minimize adverse drug reactions 4
- Exercise extra caution when increasing doses in elderly patients 1
- Elderly patients have significantly greater risk of adverse drug reactions compared to younger populations 4
Efficacy by Indication
Depression
- Venlafaxine 75-225 mg/day demonstrates superior efficacy to placebo, with remission rates of 37% versus 18% for placebo 2
- At least as effective as fluoxetine and paroxetine for major depression 2
- More effective than venlafaxine immediate-release formulation 2
Anxiety Associated with Depression
- Venlafaxine is specifically effective for depression with associated anxiety symptoms 3
- Dose-related improvements in anxiety symptoms (HAM-D Anxiety-Psychic Item and Anxiety-Somatization Factor) at 150-200 mg/day 3
- Venlafaxine 75-225 mg/day showed significantly higher HAM-A response rates compared to fluoxetine 2
- Doses of 225-375 mg/day have been used successfully in anxious and anxious-apathic depression with 83.3% response rates 5
Maintenance Treatment
- Continue treatment for 4-12 months after first episode of major depression 4
- Patients with recurrent depression (3+ episodes) benefit from prolonged maintenance treatment 4
- Venlafaxine maintenance therapy (75-225 mg/day) significantly reduces depression recurrence rates compared to placebo over 12-24 months 4
Common Adverse Effects
- Most frequent: nausea, dizziness, somnolence, insomnia, dry mouth, asthenia, sweating, and abnormal ejaculation 2, 3
- Generally well tolerated with similar adverse event profile to SSRIs 2
- Modest increases in blood pressure may occur, particularly at higher doses 6
- Fewer anticholinergic and CNS adverse effects compared to tricyclic antidepressants 6
Discontinuation Protocol
- Gradually reduce dose rather than abrupt cessation to minimize withdrawal symptoms 1
- If intolerable symptoms occur after dose reduction, resume previous dose and decrease more gradually 1
- Monitor for discontinuation symptoms including dizziness, sensory disturbances, agitation, anxiety, and flu-like symptoms 1
Critical Drug Interactions
- Allow at least 14 days between discontinuing an MAOI and starting venlafaxine 1
- Allow at least 7 days after stopping venlafaxine before starting an MAOI 1
- Do not start venlafaxine in patients receiving linezolid or intravenous methylene blue due to serotonin syndrome risk 1