How should venlafaxine be tapered and discontinued safely?

How to Discontinue Venlafaxine

Venlafaxine must be tapered gradually over weeks to months—never stopped abruptly—because discontinuation syndrome occurs frequently and can be severe, including symptoms that may resemble stroke or cause significant functional impairment. 1, 2

Critical Safety Framework

Abrupt discontinuation is never appropriate and carries serious risks:

• Venlafaxine has a particularly high risk of discontinuation syndrome compared to other antidepressants due to its short elimination half-life 1
• Withdrawal symptoms can begin within hours of a missed dose and may include dizziness, nausea, headache, fatigue, dysphoria, paresthesias ("electric shock" sensations), flu-like symptoms, and in severe cases hallucinations 3, 4, 5
• Symptoms may be severe enough to impair driving and coordination skills 6
• The FDA label explicitly warns that abrupt discontinuation can be associated with certain symptoms and medication should be tapered "as rapidly as is feasible" while recognizing discontinuation risks 2

Recommended Tapering Protocol

Standard taper approach:

• Reduce venlafaxine by 10-25% of the current dose every 1-2 weeks for patients on the medication less than one year 1
• For patients on venlafaxine longer than one year, slow the taper to 10% of the current dose per month 1
• Always calculate reductions as a percentage of the current dose, not the original dose, to prevent disproportionately large final decrements 1
• The taper rate must be determined by patient tolerance, not a rigid schedule—pauses are acceptable and often necessary when withdrawal symptoms emerge 1
• Expect the entire taper to take a minimum of 6-12 months, and potentially longer for long-term users 1

Example tapering schedule for a patient on venlafaxine 150 mg/day:

• Weeks 1-2: Reduce to 112.5 mg/day (25% reduction)
• Weeks 3-4: Reduce to 84-90 mg/day (20-25% of current dose)
• Continue reducing by 10-25% of current dose every 1-2 weeks as tolerated 1

Alternative Strategy: Switch to Fluoxetine

For patients experiencing severe withdrawal symptoms during direct taper:

• Consider cross-tapering to fluoxetine, which has a longer half-life and provides "built-in" tapering due to its active metabolite 7
• This is a simple, effective, and inexpensive method for patients who cannot tolerate direct venlafaxine tapering 7
• Gradually reduce venlafaxine while introducing fluoxetine, then taper fluoxetine more easily due to its pharmacokinetic properties 7

Monitoring Requirements

Follow patients closely throughout the taper:

• Schedule visits at least monthly during the taper, with more frequent contact during difficult phases 1
• Monitor specifically for withdrawal symptoms: dizziness, nausea, headache, fatigue, paresthesias, insomnia, anxiety, tremor, sweating, mood disturbances 1, 5
• Screen for return of original psychiatric symptoms, emergence of new psychiatric symptoms, and suicidal ideation 2
• Assess functional capacity—inability to maintain daily activities signals need to slow or pause the taper 1

Managing Withdrawal Symptoms

If clinically significant withdrawal symptoms emerge:

• Immediately slow the taper rate or pause entirely at the current dose 1
• Maintain the current dose for 2-4 weeks while optimizing supportive measures 1
• Consider restarting the prior dose and then tapering even more slowly 5
• Provide symptomatic management: analgesics for headache/myalgias, antiemetics for nausea, sleep hygiene measures for insomnia 5
• Do not abandon the patient—maintenance at a reduced dose is an acceptable outcome if complete discontinuation proves intolerable 1

Adjunctive Strategies to Improve Success

Integrate non-pharmacologic support:

• Cognitive-behavioral therapy (CBT) during the taper significantly increases success rates and should be incorporated whenever possible 1
• Patient education about venlafaxine discontinuation risks and benefits of tapering improves outcomes and engagement 1
• Consider gabapentin (starting 100-300 mg at bedtime or three times daily, titrated by 100-300 mg every 1-7 days) to mitigate withdrawal symptoms 1

When to Refer to a Specialist

Immediate specialist referral is indicated for:

• History of withdrawal seizures 1
• Unstable psychiatric comorbidities 1
• Co-occurring substance use disorders 1
• Previous unsuccessful office-based tapering attempts 1
• Severe withdrawal symptoms that cannot be managed in primary care 1

Critical Pitfalls to Avoid

• Never taper too quickly—even a 10% reduction every 3 days resulted in only 24% of patients successfully completing withdrawal 1
• Never use straight-line percentage reductions from the starting dose—this creates disproportionately large final decrements 1
• Never stop abruptly, even if the patient misses doses—venlafaxine withdrawal can occur after missing a single dose 3, 6
• Never abandon the therapeutic relationship if tapering is unsuccessful—consider maintenance therapy at a reduced dose 1
• Warn patients explicitly about impaired driving and coordination during withdrawal 6