What is the safest way to taper off alprazolam (Xanax) 0.5 mg BID (twice daily) in a patient also taking paroxetine (Paxil) 20 mg BID (twice daily) who has had a fall possibly due to sedation?

Tapering Alprazolam After Fall in Patient on Paroxetine

Given the fall risk in this elderly patient, alprazolam should be tapered gradually at a rate no faster than 0.25 mg every 1-2 weeks, which is safer and better tolerated than the FDA's standard recommendation, particularly for patients who have been on treatment for months. 1

Immediate Safety Assessment

Before initiating the taper, recognize that this patient is at high risk for further falls due to:

• Benzodiazepine-induced psychomotor impairment, cognitive decline, and increased fall risk, which are particularly pronounced in elderly patients who exhibit higher plasma concentrations due to reduced clearance 1, 2
• The combination of alprazolam with paroxetine (an SSRI) may potentiate sedation, though paroxetine itself does not significantly alter alprazolam pharmacokinetics 3
• Current total daily dose of 1 mg alprazolam (0.5 mg BID) places the patient in a moderate-risk category for withdrawal symptoms during discontinuation 4

Recommended Tapering Protocol

The safest approach involves a conservative reduction schedule:

• Reduce by 0.25 mg every 1-2 weeks as recommended by the Substance Abuse and Mental Health Services Administration, which is more conservative than the FDA's standard recommendation of 0.5 mg every 3 days 1
• Practical schedule for this patient (starting at 1 mg/day total):
  • Weeks 1-2: 0.5 mg in morning, 0.25 mg in evening (0.75 mg/day total)
  • Weeks 3-4: 0.25 mg twice daily (0.5 mg/day total)
  • Weeks 5-6: 0.25 mg once daily
  • Week 7+: Discontinue 1

The FDA label states that dosage should be decreased by no more than 0.5 mg every 3 days, but explicitly notes that some patients may require a slower dose reduction, particularly those on treatment for months. 4

Critical Monitoring During Taper

Watch for benzodiazepine withdrawal symptoms at each visit (weekly during taper):

Physical Withdrawal Symptoms 5

• Tremor, diaphoresis, agitation, insomnia
• Myoclonus, diffuse pain/hyperalgesia
• Hypertension, cramping/diarrhea
• Pupillary dilation

Affective Withdrawal Symptoms 5

• Dysphoria, anhedonia, anxiety
• Depression, hopelessness, or suicidal ideation (requires immediate intervention)

Unlike sedative withdrawal, seizures and delirium occur only rarely in benzodiazepine withdrawal except in seriously ill patients, but remain a theoretical risk. 5

Managing the Paroxetine Component

Continue paroxetine 20 mg BID (40 mg/day total) unchanged during the alprazolam taper:

• The paroxetine provides the definitive long-term treatment for anxiety and will help mitigate rebound anxiety during benzodiazepine withdrawal 2
• SSRIs like paroxetine are the evidence-based first-line treatment for anxiety disorders, providing sustained benefit beyond acute symptom control 2
• Paroxetine does not significantly alter alprazolam clearance, so no dose adjustment of alprazolam is needed based on this interaction 3

Alternative Strategies if Taper Proves Difficult

If the patient experiences intolerable withdrawal symptoms or severe rebound anxiety:

Option 1: Slow the Taper Further

• Extend the reduction intervals to every 2-3 weeks instead of 1-2 weeks 1
• Consider even smaller decrements (0.125 mg reductions) if 0.25 mg steps are not tolerated 1

Option 2: Add Adjunctive Sleep Support

• Consider low-dose trazodone 25-50 mg at bedtime if insomnia becomes problematic during taper, as it addresses sleep without tolerance issues and has minimal anticholinergic effects 2

Option 3: Consider Buspirone Augmentation

• Add buspirone 5 mg twice daily, titrating to 15-30 mg/day over 2-4 weeks as a non-benzodiazepine anxiolytic that does not cause sedation, cognitive impairment, or fall risk 1, 6
• Critical caveat: Buspirone requires 2-4 weeks to manifest therapeutic effects and has no immediate anxiolytic effect, so it must be started well before completing the alprazolam taper 6

Common Pitfalls to Avoid

Do not taper too rapidly:

• The most common reason for taper failure is moving too quickly, leading to withdrawal symptoms that prompt resumption of the benzodiazepine 5, 1
• A controlled study showed that a slower taper schedule was associated with reduced withdrawal symptoms, though both fast and slow tapers achieved similar completion rates 4

Do not abruptly discontinue:

• Abrupt discontinuation or rapid taper can precipitate withdrawal seizures, though this is rare 4
• Rebound anxiety and panic attacks are common with rapid discontinuation and may be misinterpreted as treatment failure rather than withdrawal 4

Do not use flumazenil (benzodiazepine antagonist):

• Flumazenil can precipitate severe withdrawal including seizures in benzodiazepine-dependent patients and is contraindicated in this setting 5
• Flumazenil is only appropriate for reversing procedural sedation in patients without dependence 5

Reassessment Timeline

Schedule follow-up visits:

• Weekly during active taper phase to assess withdrawal symptoms, fall risk, anxiety control, and medication adherence 2
• At 4-6 weeks after completing taper to ensure stability on paroxetine monotherapy and confirm resolution of any withdrawal symptoms 2
• Monitor for depression emergence, as anxiety disorders can unmask or trigger major depressive episodes requiring full antidepressant optimization 2