What is the recommended protocol for discontinuing venlafaxine (Effexor) in a patient taking 75 mg?

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Venlafaxine 75 mg Discontinuation Protocol

Venlafaxine 75 mg should be tapered gradually rather than stopped abruptly, as it is a short-acting SNRI with high risk of discontinuation syndrome. 1

Recommended Tapering Strategy

Reduce the dose by 37.5 mg every 4-7 days, which means:

  • Week 1-2: Reduce from 75 mg to 37.5 mg daily 2
  • Week 2-3: Continue 37.5 mg for at least 4 days before stopping completely 2
  • Monitor closely for discontinuation symptoms throughout the taper 1

The FDA label specifies that dose changes should occur at intervals of no less than 4 days, which provides the minimum safe tapering interval 2. However, given that venlafaxine is specifically identified as a short-acting agent with marked discontinuation syndromes 1, a more conservative 7-day interval between reductions may be prudent for patients with prior withdrawal sensitivity.

Why Gradual Tapering is Critical

Venlafaxine has one of the highest risks of discontinuation syndrome among antidepressants due to its short half-life and dual mechanism 1. Discontinuation symptoms are most marked with short-acting agents like venlafaxine and paroxetine 1. Severe withdrawal reactions can occur even after missing a single dose 3, 4.

Common discontinuation symptoms include:

  • Dizziness, nausea, and headache (most frequent) 3, 4, 5
  • Fatigue, irritability, and dysphoria 3, 5
  • Anxiety, abnormal dreams, and hyperhidrosis 5
  • In severe cases, symptoms may mimic stroke 4

Alternative Strategy: Fluoxetine Bridge

If standard tapering fails due to intolerable withdrawal symptoms, consider switching to fluoxetine before discontinuation 6. Fluoxetine's long half-life (4-6 days) provides built-in tapering and can significantly reduce discontinuation symptoms 6. This involves:

  • Cross-taper to fluoxetine 20 mg daily while reducing venlafaxine 6
  • Continue fluoxetine for 1-2 weeks after venlafaxine is stopped 6
  • Fluoxetine can then be stopped without tapering due to its long half-life 6

Critical Monitoring During Discontinuation

Monitor for discontinuation symptoms at each dose reduction, particularly:

  • Within 24-48 hours after dose reduction (peak symptom onset) 3, 4
  • Assess using structured tools if available (DESS checklist scores increase significantly after venlafaxine cessation) 5
  • If severe symptoms emerge, resume the previous dose and slow the taper further 7, 4

Common Pitfalls to Avoid

Never stop venlafaxine abruptly, even at low doses like 75 mg 1, 8. Studies show 78% of patients experience adverse events when venlafaxine is discontinued without tapering, compared to 22% with placebo 8.

Do not assume 75 mg is "low enough" to stop without tapering—discontinuation syndrome severity is related to the drug's pharmacokinetics (short half-life), not just the dose 1, 3.

If the patient misses 3 or more consecutive doses, restart at a lower dose (37.5 mg) rather than resuming 75 mg, to minimize adverse effects 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Withdrawal reactions associated with venlafaxine.

The Australian and New Zealand journal of psychiatry, 1998

Research

Venlafaxine withdrawal syndrome.

Psychiatria Danubina, 2011

Research

[Discontinuing venlafaxine by switching to fluoxetine].

Tijdschrift voor psychiatrie, 2018

Guideline

Venlafaxine Dosing After Missed Doses

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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