Is it safe for a patient with Opioid Use Disorder (OUD) and chronic pain, already on Subutex (buprenorphine) 8mg at 8am and 8pm and Lyrica (pregabalin) 200mg at 10am and 4pm, to take Ativan (lorazepam) 1mg at 6am, 12pm, 6pm, and 12am while tapering off Ativan?

Safety of Combined Ativan, Subutex, and Lyrica Regimen

This medication regimen carries significant risk and requires immediate clinical reassessment, as the CDC explicitly warns against concurrent benzodiazepines and buprenorphine due to life-threatening respiratory depression and overdose risk, though treatment should not be categorically denied if proper monitoring and risk mitigation strategies are implemented. 1

Critical Safety Concerns

Benzodiazepine-Buprenorphine Interaction

• The FDA black box warning states that concomitant use of buprenorphine and benzodiazepines increases the risk of respiratory depression, coma, and death. 2
• Many post-marketing reports of life-threatening respiratory depression and death with buprenorphine involved concomitant benzodiazepine use. 2
• The CDC 2022 guidelines specifically recommend using "particular caution when prescribing benzodiazepines or other sedating medications with opioid pain medication" and to "avoid concurrent opioids and benzodiazepines whenever possible." 1

The Paradox of Treatment Access

• Medication-assisted treatment for OUD should not be categorically denied to patients taking benzodiazepines, as prohibiting treatment poses an even greater risk of morbidity and mortality from untreated OUD alone. 2
• The key is implementing appropriate risk mitigation strategies rather than refusing treatment. 2

Risk Mitigation Algorithm

Step 1: Patient Education (Mandatory)

• Educate the patient about the specific risks of combining Ativan with Subutex, including overdose and death. 2
• Document this education in the medical record. 2

Step 2: Assess Sedation Before Each Dose

• If the patient is sedated at the time of buprenorphine dosing, delay or omit the buprenorphine dose. 2
• Monitor for signs of respiratory depression, excessive drowsiness, or altered mental status. 2

Step 3: Benzodiazepine Taper Strategy

• Cessation of benzodiazepines is preferred in most cases of concomitant use. 2
• For patients on 4mg daily Ativan (the regimen described), gradually taper to the lowest effective dose rather than abrupt discontinuation. 2
• Consider monitoring in a higher level of care for the taper if clinically indicated. 2
• There is no evidence to support dose limitations or arbitrary caps of buprenorphine as a strategy to address benzodiazepine use. 2

Step 4: Alternative Treatments for Anxiety

• Benzodiazepines are not the treatment of choice for anxiety or insomnia in patients on buprenorphine treatment. 2
• Consider alternative medications including trazodone, tricyclic antidepressants, gabapentin (note: patient already on Lyrica/pregabalin), or mirtazapine for anxiety and insomnia. 1
• Pregabalin (Lyrica) at 400mg daily may already provide some anxiolytic benefit. 1

Step 5: Enhanced Monitoring Requirements

• Coordinate care with all prescribers to ensure awareness of the complete medication regimen. 2
• Check prescription drug monitoring program (PDMP) data to assess for additional controlled substances. 1, 2
• Conduct toxicology screening for prescribed and illicit benzodiazepines to confirm adherence and detect supplementation. 2
• Confirm patients are taking medications as prescribed and not diverting. 2

Specific Concerns with This Regimen

Ativan Dosing Schedule

• The 4mg daily total dose (1mg four times daily) represents a moderate-to-high benzodiazepine dose when combined with buprenorphine. 2
• The frequent dosing schedule (every 6 hours) may complicate monitoring for sedation. 2

Subutex vs. Suboxone Consideration

• The patient is on Subutex (buprenorphine alone) rather than Suboxone (buprenorphine/naloxone). 1
• Buprenorphine/naloxone is preferred over buprenorphine alone due to abuse-deterrent properties. 1
• Consider switching to buprenorphine/naloxone unless there is a specific contraindication. 1

Lyrica (Pregabalin) Addition

• Pregabalin 400mg daily is within therapeutic range for pain management. 1
• Pregabalin can potentiate CNS depression when combined with opioids and benzodiazepines, though this is less pronounced than benzodiazepine-opioid interactions. 1
• Monitor for increased sedation with this three-drug combination. 2

Clinical Decision Framework

If Patient is Stable on Current Regimen

• Implement all monitoring strategies outlined above. 2
• Initiate slow benzodiazepine taper with goal of discontinuation. 2
• Increase frequency of clinical assessments during taper. 1

If Patient Shows Signs of Sedation or Respiratory Depression

• Immediately delay or omit buprenorphine doses. 2
• Consider emergency medical evaluation. 2
• Reassess the necessity of continuing all three medications. 2

If Benzodiazepine is for Documented Anxiety/Insomnia

• Ensure appropriate diagnosis before continuing benzodiazepine. 2
• Trial alternative non-benzodiazepine anxiolytics. 2
• Consider that buprenorphine itself may have antidepressant and anxiolytic properties. 3

Common Pitfalls to Avoid

• Do not arbitrarily reduce buprenorphine dose as a strategy to manage benzodiazepine risk—this lacks evidence and may destabilize OUD treatment. 2
• Do not abruptly discontinue benzodiazepines without a taper plan, as this can cause dangerous withdrawal. 2
• Do not assume the patient cannot be treated with buprenorphine simply because they take benzodiazepines. 2
• Do not prescribe this combination without documented patient education about overdose risk. 2

Bottom Line

This regimen can be continued with intensive monitoring and a concrete plan to taper and discontinue the benzodiazepine, but it cannot be considered safe for long-term concurrent use without these interventions. 1, 2 The priority is maintaining OUD treatment with buprenorphine while systematically reducing benzodiazepine exposure through gradual taper and substitution with safer alternatives. 2