How to taper a patient off 2 mg alprazolam (three times a day) after being on it for over 3 years?

Tapering Alprazolam 2 mg TID After 3+ Years

For a patient on alprazolam 2 mg three times daily (6 mg/day total) for over 3 years, implement a very slow taper reducing by 10% of the current dose every 2-4 weeks, which will take approximately 6-12 months or longer, with the benzodiazepine taper taking absolute priority if the patient is also on opioids. 1

Critical Safety Considerations

Benzodiazepine withdrawal carries greater risks than opioid withdrawal and can cause seizures and death if discontinued abruptly. 1, 2 The FDA label explicitly warns that abrupt discontinuation can lead to withdrawal seizures, even after brief therapy at lower doses. 2

• If this patient is also taking opioids, taper the alprazolam first due to the higher mortality risk associated with benzodiazepine withdrawal compared to opioid withdrawal. 1
• Abrupt discontinuation is never appropriate and is equivalent to suddenly stopping antihypertensives or antihyperglycemics in terms of medical inappropriateness. 3

Recommended Tapering Protocol

Initial Taper Rate

Reduce by 10% of the current dose every 2-4 weeks, not 10% of the original dose. 1 This means:

• Week 1-2: Reduce from 6 mg/day to 5.4 mg/day (0.6 mg reduction)
• Week 3-4: Reduce from 5.4 mg/day to 4.86 mg/day (0.54 mg reduction)
• Continue this pattern, with each reduction being 10% of the previous dose 1

The FDA label suggests decreasing by no more than 0.5 mg every 3 days, but this is too rapid for long-term users and should be disregarded in favor of the slower guideline-based approach. 2

Why This Slow Approach

• For patients on benzodiazepines for ≥1 year, tapers of 10% per month or slower are better tolerated than rapid tapers. 1
• Research shows that only 47% of patients successfully discontinued alprazolam after long-term use with standard tapering, and 33% were unable to complete the taper. 4, 5
• The taper rate must be determined by patient tolerance, not a rigid schedule. 1

Managing Withdrawal Symptoms

Expected Withdrawal Symptoms

Monitor for both physical and psychological symptoms 1:

• Physical: Tremor, sweating, tachycardia, hypertension, muscle cramps, insomnia, headache, weakness, nausea, diarrhea
• Psychological: Anxiety, dysphoria, depression, irritability, confusion, suicidal ideation

Distinguishing Withdrawal from Relapse

• Withdrawal symptoms typically appear toward the end of taper or shortly after dose reduction and decrease with time. 2
• Relapse/rebound involves return of original anxiety symptoms, often appearing early and persisting. 2
• Research shows 27% experience rebound panic attacks and 35% experience distinct withdrawal syndrome during alprazolam discontinuation. 6

Adjunctive Medications

Consider these pharmacological supports:

• Gabapentin: Start 100-300 mg at bedtime or TID, increase by 100-300 mg every 1-7 days as tolerated to mitigate withdrawal symptoms. 1
• Carbamazepine: Can help with withdrawal symptoms, though it may affect alprazolam metabolism. 1
• Pregabalin: Has shown benefit in facilitating benzodiazepine tapering. 1
• SSRIs (e.g., paroxetine): May manage underlying anxiety during tapering. 1

Alternative strategy: Consider switching to a longer-acting benzodiazepine like chlordiazepoxide or diazepam before tapering, as this may provide smoother withdrawal. 7 However, this adds complexity and the direct taper approach is generally preferred.

Non-Pharmacological Support

Integrate cognitive behavioral therapy (CBT) during the taper, as it increases success rates significantly. 1 Additional supportive measures include:

• Mindfulness and relaxation techniques 1
• Sleep hygiene education if insomnia emerges 1
• Exercise and fitness training (though specific evidence for benzodiazepine tapering is limited) 3

Monitoring Requirements

Follow up at least monthly during the taper, with more frequent contact during difficult phases. 1 At each visit:

• Assess withdrawal symptoms and their severity
• Screen for depression, anxiety, and suicidal ideation 1
• Monitor for substance use disorders that may emerge 1
• Adjust taper rate based on patient tolerance

If withdrawal symptoms are significant, slow the taper further or pause temporarily. 1 Pauses are acceptable and often necessary—the taper can be restarted when the patient is ready. 1

When to Refer to Specialist

Refer immediately if the patient has 1:

• History of withdrawal seizures
• Unstable psychiatric comorbidities
• Co-occurring substance use disorders
• Previous unsuccessful office-based tapering attempts

Key Pitfalls to Avoid

• Never taper too quickly: Research shows that even a 10% reduction every 3 days (as suggested in older studies) resulted in only 24% of patients completing withdrawal successfully. 8
• Never abandon the patient: Offering a safe taper is a medical obligation, even if the patient is difficult. 3
• Don't use percentage of original dose: Each reduction should be 10% of the current dose to prevent disproportionately large final reductions. 1
• Don't ignore patient fears: Address anxiety about the taper proactively and set realistic expectations from the start. 3

Realistic Timeline and Goals

This taper will likely take 6-12 months minimum, and possibly longer. 1 The goal may not be complete discontinuation for all patients—some may benefit from a lower maintenance dose where functional benefits outweigh risks. 1 Patient agreement and interest in tapering is a key component of success. 3

Warn the patient that if they return to previous doses after tolerance is lost, overdose risk is significantly increased. 1