Can I restart venlafaxine in a patient who previously tolerated it, and how should it be dosed and monitored?

Restarting Venlafaxine After Previous Tolerance

Yes, you can restart venlafaxine in a patient who previously tolerated it, but if the patient has missed 3 or more consecutive doses, restart at 37.5 mg daily rather than resuming the previous dose to minimize adverse effects. 1

Restarting Protocol After Treatment Gap

If the patient missed fewer than 3 doses:

• Resume the previous therapeutic dose directly 2
• Monitor closely for the first 2-4 weeks 3

If the patient missed 3 or more consecutive doses:

• Restart at 37.5 mg daily for the first week 1
• Increase to 75 mg daily after 1 week if tolerated 4, 2
• For doses above 75 mg, titrate by 37.5-75 mg increments every 4-7 days 2
• Maximum dose is 375 mg/day in divided doses 2

Critical Monitoring Requirements

Cardiovascular monitoring is mandatory:

• Check blood pressure and pulse before restarting and at each follow-up visit 5
• Venlafaxine causes dose-dependent blood pressure elevation that may require discontinuation 5
• For patients over 40 years with cardiac risk factors, consider baseline ECG 5
• Monitor particularly closely during weeks 2-4 after restarting 3

Watch for discontinuation syndrome if the gap was recent:

• If the patient stopped abruptly and is experiencing withdrawal symptoms (dizziness, nausea, headache, irritability), restarting venlafaxine will rapidly resolve these symptoms 1, 6
• Symptoms typically emerge within hours to days after the last dose and resolve within 1-2 weeks of restarting 3, 6

Efficacy Assessment Timeline

Allow adequate time before judging effectiveness:

• Wait 4-6 weeks at the therapeutic dose before fully assessing efficacy 3
• For depression, most patients respond to 75-225 mg/day 2, 7
• More severely depressed patients may require up to 375 mg/day 2

Special Populations Requiring Dose Adjustment

Hepatic impairment:

• Reduce total daily dose by 50% in mild to moderate hepatic impairment 2
• May need greater reduction in cirrhosis due to individual variability 2

Renal impairment:

• Reduce total daily dose by 25% if GFR 10-70 mL/min 2
• Reduce by 50% in patients on hemodialysis 2

Elderly patients:

• No automatic dose reduction required based on age alone 2
• Exercise extra caution when increasing doses 2

Drug Interactions to Consider

Avoid or use extreme caution with:

• MAOIs: Allow 14 days after stopping MAOI before starting venlafaxine, and 7 days after stopping venlafaxine before starting MAOI 2
• Linezolid or IV methylene blue: Do not start venlafaxine in patients receiving these agents due to serotonin syndrome risk 2
• Tamoxifen: Venlafaxine has minimal effects on tamoxifen metabolism, making it preferred over paroxetine or fluoxetine in breast cancer patients 5

Common Pitfalls to Avoid

Never restart at the full previous dose after a significant gap:

• This increases risk of adverse effects and blood pressure spikes 1
• The conservative approach of starting at 37.5 mg after 3+ missed doses prevents complications 1

Do not abruptly discontinue if restarting fails:

• Venlafaxine has one of the highest discontinuation syndrome risks among antidepressants due to its short half-life 1, 6
• Always taper by 37.5 mg every 4-7 days when stopping 1
• If severe symptoms emerge during tapering, resume the previous dose and slow the taper further 1

Monitor for serotonin syndrome:

• Risk exists even with monotherapy at low doses (37.5 mg/day) 8
• Symptoms include restlessness, tremor, shivering, diarrhea, tachycardia, and myoclonus 8
• Higher risk if combining with other serotonergic agents 8