Management of Withdrawal from GHB and Xanax (Alprazolam)
For patients withdrawing from both GHB and alprazolam (Xanax), lorazepam (Ativan) is preferred over clonazepam (Klonopin) due to its intermediate half-life, predictable metabolism independent of hepatic function, and lack of active metabolites—critical advantages when managing polydrug withdrawal with unpredictable pharmacokinetics. 1
Rationale for Lorazepam Selection
Pharmacokinetic Advantages
- Lorazepam is specifically recommended for patients with complex withdrawal scenarios including those with liver dysfunction, advanced age, obesity, or polydrug use 1
- Intermediate-acting benzodiazepines like lorazepam are safer than long-acting agents (including clonazepam) in patients with hepatic dysfunction, which is common in substance use disorders 1
- Lorazepam undergoes glucuronide conjugation rather than oxidative metabolism, making its clearance more predictable in compromised patients 1
- No active metabolites accumulate with lorazepam, unlike diazepam or clonazepam, reducing risk of oversedation 1
Clinical Evidence for Dual Withdrawal
GHB withdrawal presents similarly to alcohol/sedative-hypnotic withdrawal with anxiety, agitation, tremor, and potential for delirium tremens 2. Daily GHB users develop tolerance and dependence requiring around-the-clock dosing, with abrupt discontinuation causing withdrawal delirium and psychosis 2.
Alprazolam (Xanax) requires special consideration as a triazolobenzodiazepine with unique withdrawal characteristics 3. High-dose alprazolam withdrawal should be managed differently than other benzodiazepines, but the principles of cross-tolerance allow substitution with lorazepam 3.
Recommended Treatment Protocol
Initial Assessment and Dosing
- Start lorazepam at 6-12 mg/day divided into multiple doses for moderate to severe withdrawal 1
- Use symptom-triggered dosing with CIWA-Ar scale (score >8 indicates moderate withdrawal, ≥15 indicates severe) rather than fixed schedules 1
- Administer lorazepam 1-4 mg IV/IM/PO every 4-8 hours initially, adjusting based on withdrawal severity 1
Tapering Strategy
- Taper lorazepam gradually following resolution of acute withdrawal symptoms, typically over several weeks 1
- For alprazolam component: account for its potency by titrating at 0.5 mg equivalents when calculating cross-taper 3
- Reduce dose by approximately 10% per day for inpatient management or more gradually (25% weekly) for outpatient settings 1, 3
Monitoring and Adjunctive Treatment
- Thiamine 100-300 mg/day must be administered to all patients to prevent Wernicke encephalopathy, continued for 2-3 months 1
- Monitor for propylene glycol toxicity if using high-dose lorazepam infusions (>10 mg/hr), though this is primarily a concern with continuous infusions 1
- Assess for breakthrough symptoms every 1-2 hours initially and provide additional bolus doses as needed 1
Why Not Clonazepam (Klonopin)?
Clonazepam's long half-life (20-50 hours) and active metabolites create unpredictable accumulation in polydrug withdrawal scenarios 1. While long-acting benzodiazepines theoretically provide smoother coverage, the combination of GHB (requiring frequent dosing due to short half-life) and alprazolam (already a potent benzodiazepine) creates complex pharmacokinetics where lorazepam's predictability is advantageous 1.
Long-acting benzodiazepines like clonazepam are recommended for uncomplicated alcohol withdrawal to prevent seizures 1, but this dual withdrawal scenario requires the flexibility and safety profile of an intermediate-acting agent 1.
Critical Pitfalls to Avoid
- Never abruptly discontinue benzodiazepines after stabilization—gradual withdrawal over >1 month is essential to prevent rebound symptoms, dyskinesias, and potential neuroleptic malignant syndrome-like presentations 1
- Avoid benzodiazepine use beyond 10-14 days for maintenance due to abuse potential, particularly high in this population 1
- Do not use fixed-dose schedules—symptom-triggered regimens prevent drug accumulation and are more effective 1
- Beware of paradoxical agitation, which occurs in approximately 10% of patients treated with benzodiazepines 1
- Monitor for respiratory depression, especially given the polydrug history and potential for concurrent substance use 1
Inpatient vs. Outpatient Management
Inpatient treatment is strongly recommended for this dual withdrawal scenario given the risk of delirium tremens, seizures, and the documented severity of GHB withdrawal in daily users 1, 2. Psychiatric consultation should be obtained for evaluation, acute management, and long-term abstinence planning 1.