What is a safe medication schedule for a patient with alcohol use disorder and opioid use disorder (OUD) being treated with Lyrica (pregabalin) 200mg twice daily, Ativan (lorazepam) 1mg four times daily, and Subutex (buprenorphine) 8mg twice daily?

Safe Medication Schedule for Alcohol Use Disorder and Opioid Use Disorder

Critical Safety Concern: This Polypharmacy Regimen Requires Immediate Risk Mitigation

This combination of Lyrica (pregabalin) 200mg BID, Ativan (lorazepam) 1mg QID, and Subutex (buprenorphine) 8mg BID poses significant risk for respiratory depression, sedation, and overdose due to concurrent central nervous system depressants, and the regimen should be modified to prioritize patient safety. 1

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Primary Recommendation: Taper and Discontinue Benzodiazepines

The CDC guideline explicitly states that clinicians should avoid concurrent opioids and benzodiazepines whenever possible, and when tapering is required, it is safer to taper benzodiazepines gradually while continuing opioid maintenance therapy. 1

Benzodiazepine Tapering Protocol:

• Lorazepam 1mg QID (4mg/day total) must be tapered gradually to avoid withdrawal complications including seizures, delirium tremens, and rebound anxiety 1
• Week 1-2: Reduce to 0.75mg QID (3mg/day total) 1
• Week 3-4: Reduce to 0.5mg QID (2mg/day total) 1
• Week 5-6: Reduce to 0.5mg TID (1.5mg/day total) 1
• Week 7-8: Reduce to 0.5mg BID (1mg/day total) 1
• Week 9-10: Reduce to 0.25mg BID (0.5mg/day total) 1
• Week 11-12: Discontinue 1
• Offer evidence-based psychotherapies (CBT) and specific antidepressants or other non-benzodiazepine medications for anxiety during and after taper 1

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Buprenorphine (Subutex) Dosing Schedule

Continue buprenorphine 8mg BID (16mg/day total) as prescribed for opioid use disorder maintenance therapy. 1

Timing:

• Morning dose: 8mg sublingual at 8:00 AM 1
• Evening dose: 8mg sublingual at 8:00 PM 1
• Maintain consistent 12-hour intervals 1

Key Considerations:

• Buprenorphine maintenance therapy should not be withheld or interrupted as it reduces nonmedical opioid use, improves treatment retention, and reduces mortality 1, 2
• Verify doses with the prescribing physician or treatment program 1
• Monitor for precipitated withdrawal if patient has used full opioid agonists within 12-24 hours 1

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Pregabalin (Lyrica) Dosing Schedule

Pregabalin 200mg BID carries significant abuse potential in patients with opioid use disorder and should be carefully monitored or reconsidered. 3

If Continuing Pregabalin:

• Morning dose: 200mg at 8:00 AM (with food to reduce GI upset) 1
• Evening dose: 200mg at 8:00 PM 1
• Total daily dose: 400mg/day 1

Critical Warnings:

• 12.1% of patients with opioid dependency abuse pregabalin without medical indication 3
• Pregabalin produces dose-dependent dizziness and sedation, which is amplified when combined with other CNS depressants 1
• Requires dosage reduction in renal insufficiency 1
• If prescribed for alcohol use disorder, evidence shows benefit at 150-450mg/day, but mixed results exist 4, 5
• If prescribed for neuropathic pain, maximum dose is 600mg/day (200mg TID or 300mg BID) 1

Indication Verification Required:

• If pregabalin is prescribed for alcohol use disorder: Continue with close monitoring for abuse 4, 5
• If pregabalin is prescribed for neuropathic pain: Ensure documented neuropathic pain diagnosis 1
• If no clear indication exists: Consider discontinuation given high abuse potential in this population 3

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Integrated Daily Schedule (During Benzodiazepine Taper)

Week 1-2 Example:

• 8:00 AM: Buprenorphine 8mg SL + Pregabalin 200mg PO + Lorazepam 0.75mg PO 1
• 12:00 PM: Lorazepam 0.75mg PO 1
• 4:00 PM: Lorazepam 0.75mg PO 1
• 8:00 PM: Buprenorphine 8mg SL + Pregabalin 200mg PO + Lorazepam 0.75mg PO 1

Target Schedule (After Benzodiazepine Discontinuation):

• 8:00 AM: Buprenorphine 8mg SL + Pregabalin 200mg PO 1
• 8:00 PM: Buprenorphine 8mg SL + Pregabalin 200mg PO 1

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Monitoring Requirements

Immediate Safety Monitoring:

• Assess respiratory rate, oxygen saturation, and level of consciousness at each visit during concurrent use of multiple CNS depressants 1
• Provide take-home naloxone and overdose education 1
• Screen for diversion or misuse of all three medications 1, 3

Ongoing Monitoring:

• Review prescription drug monitoring program (PDMP) data at every visit 1
• Urine drug screening to detect pregabalin misuse and verify buprenorphine adherence 1, 3
• Assess for alcohol use with validated screening tools 6
• Monitor for sedation, dizziness, and cognitive impairment 1
• Evaluate benefits and harms every 3 months or more frequently 1

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Alcohol Use Disorder Management

Medications for alcohol use disorder should be offered alongside opioid maintenance therapy. 1

Evidence-Based Options:

• Extended-release naltrexone or oral naltrexone reduce alcohol use and improve outcomes 1
• Pregabalin may provide benefit for alcohol relapse prevention at 150-450mg/day, but evidence is mixed and abuse potential is high in this population 4, 5, 3
• Brief intervention strategies may help reduce alcohol intake 6

Critical Note:

• Approximately one-third of patients in opioid maintenance therapy show increased alcohol consumption, which increases mortality risk and liver toxicity 6
• Monitor liver function if alcohol use continues 6

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Common Pitfalls to Avoid

1. Never abruptly discontinue lorazepam - this can cause seizures and death 1
2. Never use mixed agonist-antagonist opioids (nalbuphine, butorphanol) - these may precipitate withdrawal in patients on buprenorphine 1
3. Never assume pregabalin is "safe" in this population - 12.1% abuse rate among opioid-dependent patients 3
4. Never fail to verify buprenorphine doses with treatment program - prevents double-dosing and diversion 1
5. Never continue benzodiazepines long-term with opioid maintenance therapy - significantly increases overdose risk 1