Naltrexone XR vs Oral — Speaker Companion

⏱️ Duration: 45 minutes 👥 Audience: PMHNPs, Addiction Psychiatry Fellows 📊 Slides: 18

Session Timing Guide

0:00–0:05 Title & Objectives
0:05–0:10 The Adherence Problem
0:10–0:18 Comparison & Cases
0:18–0:28 Initiation & XR-Open
0:28–0:38 Decision Tree & Safety
0:38–0:45 Quiz & Discussion
Slide 01

Title Slide

2 min

Speaker Notes

  • Welcome audience, establish credibility
  • Preview disclosure (off-label medications, educational purpose)
  • Set expectation: interactive cases ahead
  • Mention speaker companion materials available
💡 Tip: Make eye contact with back row during welcome. This sets an inclusive tone.
→ Transition: "Today we'll cover a critical differential in addiction psychiatry — when to choose XR versus oral naltrexone, and why the choice matters for patient outcomes."

Anticipated Questions

Q1: "Is this presentation accredited for CME?" Easy

A: Check with your institution. This content aligns with ASAM and APA guidelines but specific CME credit depends on your organization's accreditation process.

~30 seconds
Q2: "Will slides be available after the session?" Easy

A: Yes, the HTML presentation and speaker companion will be distributed via email and are available in THE CODEX clinical guides repository.

~30 seconds
Slide 02

Learning Objectives

3 min

Speaker Notes

  • Read each objective clearly
  • Emphasize the practical focus: this is about clinical decision-making, not just pharmacology
  • Note that we'll cover both OUD and AUD — the recommendations differ
🎯 Key Point: The biggest learning objective is understanding when adherence matters (OUD) vs when it doesn't (AUD with motivated patients).

Anticipated Questions

Q1: "Will we cover methadone and buprenorphine comparisons too?" Easy

A: We'll touch on buprenorphine in the XR-Open trial discussion, but this session focuses specifically on naltrexone formulations. For full MOUD comparison, see the separate buprenorphine guide.

~1 minute
Slide 03

The Adherence Problem

5 min

Speaker Notes

  • Pause on each statistic — let the numbers sink in
  • <30% vs 70-80% is a dramatic difference
  • Emphasize: this is why oral naltrexone fails for OUD
  • Quote: "The best medication is the one the patient will actually take"
💡 Tip: Ask the audience: "How many of you have prescribed oral naltrexone for OUD? How did adherence go?" This creates engagement and validates the problem.
⚠️ Watch for: Some audience members may defend oral naltrexone based on individual success stories. Acknowledge these exist but emphasize population-level data.

Anticipated Questions

Q1: "What about depot oral formulations or blister packs?" Medium

A: Blister packs and pharmacy packaging can help, but they don't solve the fundamental issue: the patient can still choose not to take it. XR naltrexone removes that choice for 30 days, which is why adherence is so much higher.

~2 minutes
Q2: "Is the adherence data from real-world or trial settings?" Medium

A: Both. The 70-80% XR adherence is from clinical trials (XR-Open) but real-world data from criminal justice settings and treatment courts show similar rates. Oral naltrexone adherence is consistently poor across all settings.

~1.5 minutes
Slide 04

Head-to-Head Comparison

5 min

Speaker Notes

  • Walk through table row by row
  • Use highlight buttons to emphasize oral vs XR columns
  • Pause on "Efficacy for OUD" — this is the critical teaching point
  • Note the cost difference is dramatic but context matters
🎯 Key Point: Oral naltrexone is pharmacologically effective but clinically ineffective for OUD due to adherence. This is a crucial distinction.
→ Transition: "Now let's look at when to choose each formulation in practice..."

Anticipated Questions

Q1: "Why is oral naltrexone 'limited' for OUD if it's the same drug?" Medium

A: It's pharmacologically effective but clinically ineffective. The drug works if taken, but patients don't take it. With OUD, the disease itself impairs the ability to adhere to daily medication. XR removes that barrier.

~2 minutes
Q2: "Is there any scenario where oral naltrexone makes sense for OUD?" Hard

A: Very limited scenarios: highly motivated patients with excellent adherence history, often in structured environments (physician health programs, professional monitoring). Even then, XR is preferred. Oral is essentially never first-line for OUD.

~2 minutes
Slide 05

When to Choose Each

4 min

Speaker Notes

  • Two-column layout allows direct comparison
  • Emphasize: for AUD, the choice is nuanced; for OUD, it's XR or don't use naltrexone
  • Criminal justice involvement is a strong indicator for XR
💡 Tip: Ask audience to think of a patient they've seen recently — which column would they fall into?

Anticipated Questions

Q1: "What about patients with both OUD and AUD?" Medium

A: Prioritize the OUD indication — use XR naltrexone. It covers both disorders. The presence of OUD trumps the AUD decision-making because adherence is critical for OUD outcomes.

~1.5 minutes
Slide 06

Case 1 — Maria (AUD)

5 min

Speaker Notes

  • Read case details slowly
  • Pause for audience to formulate answer
  • Click reveal button AFTER discussion
  • Emphasize: this is a patient who CAN adhere
⚠️ Watch for: Trainees automatically jumping to XR because "it's better." Challenge them: why pay $1,500/month when $5/month works?
🎯 Key Point: For AUD with good adherence patterns, oral naltrexone is a reasonable first-line option. Don't over-treat.

Anticipated Questions

Q1: "What if she later stops taking it?" Medium

A: Then you escalate to XR. Starting with oral doesn't close the door on XR — it just gives you a low-cost trial. If adherence becomes an issue, switch formulations.

~1 minute
Q2: "Should we discuss the Sinclair Method?" Medium

A: If time permits. Targeted use before drinking occasions may improve oral naltrexone effectiveness for AUD, though evidence is mixed. It's an option for motivated patients not seeking abstinence.

~2 minutes
Slide 07

Case 2 — James (OUD)

5 min

Speaker Notes

  • Contrast with Case 1 — this is OUD, not AUD
  • Key detail: 10 days opioid-free (meets requirement)
  • History of adherence problems + preference for non-agonist = ideal XR candidate
🎯 Key Point: This patient is ideal for XR naltrexone: opioid-free, motivated for non-agonist therapy, history of adherence problems. The 30-day blockade is a safety feature.
→ Transition: "But what if he wasn't opioid-free? That's the #1 barrier to XR naltrexone..."

Anticipated Questions

Q1: "What if he had only been opioid-free for 5 days?" Hard

A: Wait longer. The 7-14 day requirement is not arbitrary — it's based on pharmacokinetics and precipitated withdrawal risk. With fentanyl's long half-life and lipophilicity, some patients need 10-14 days. Don't rush it.

~2 minutes
Q2: "Why not buprenorphine instead?" Medium

A: Valid option. Patient preference for non-agonist therapy is the deciding factor here. Some patients specifically want to avoid opioid agonists. Both are evidence-based; shared decision-making applies.

~2 minutes
Slide 08

The Initiation Problem

5 min

Speaker Notes

  • This is the most critical safety slide
  • Emphasize: precipitated withdrawal from naltrexone is WORSE than buprenorphine
  • Walk through the 3-step process slowly
  • Naloxone challenge is essential — don't skip it
⚠️ Watch for: Audience members who think they can "eyeball" readiness. Emphasize objective measures (UDS, naloxone challenge) over clinical impression.

Anticipated Questions

Q1: "What if naloxone challenge causes withdrawal?" Hard

A: Wait longer. The patient isn't ready. Treat the precipitated withdrawal (supportive care, possibly low-dose buprenorphine if severe), and reschedule XR naltrexone for later. Do NOT proceed with injection.

~2 minutes
Q2: "Is UDS alone sufficient without naloxone challenge?" Medium

A: No. UDS can be negative while patient still has significant opioid tolerance. The naloxone challenge tests for residual physical dependence. Both are required per prescribing guidelines.

~1.5 minutes
Slide 09

The XR-Open Trial

5 min

Speaker Notes

  • XR-Open is the landmark comparative effectiveness trial
  • Key finding: harder to initiate, equivalent outcomes once started
  • 28% vs 5% initiation failure is dramatic
  • This explains why XR naltrexone hasn't replaced buprenorphine
🎯 Key Point: The challenge is getting patients through the opioid-free period — not the medication itself. Once initiated, XR naltrexone works as well as buprenorphine.

Anticipated Questions

Q1: "What happened to the 28% who couldn't initiate?" Hard

A: Most were lost to follow-up or continued using opioids and couldn't achieve the opioid-free period. This highlights the real-world challenge: XR naltrexone requires a motivated patient who can achieve abstinence — a select population.

~2 minutes
Q2: "Has there been any real-world effectiveness data since XR-Open?" Medium

A: Yes, multiple studies in criminal justice settings, treatment courts, and integrated care models show similar outcomes when initiation is supported. The key is structured initiation support.

~1.5 minutes
Slide 10

Decision Tree

4 min

Speaker Notes

  • Interactive element — let audience vote before revealing
  • Click through both branches (OUD and AUD)
  • Emphasize the different logic for each disorder
💡 Tip: Ask for a show of hands: "How many would choose XR for AUD?" Then reveal that oral is reasonable first-line.

Anticipated Questions

Q1: "Can you switch from oral to XR mid-treatment?" Easy

A: Yes, but you still need the opioid-free period and naloxone challenge. The fact they've been on oral naltrexone doesn't change the initiation requirements for XR.

~1 minute
Slide 11

Cost & Insurance Reality

4 min

Speaker Notes

  • Acknowledge the elephant in the room: cost
  • $1-5 vs $1,000-1,500 is a massive difference
  • But emphasize cost-effectiveness, not just cost
  • Mention Alkermes patient assistance program
🎯 Key Point: Don't let cost alone drive the decision for OUD. The cost of relapse (overdose, hospitalization, lost productivity) far exceeds the medication cost difference.

Anticipated Questions

Q1: "How do I get XR naltrexone covered?" Medium

A: Document failure of oral naltrexone (if applicable), emphasize adherence concerns, and cite XR-Open evidence. Many insurers require prior auth but will approve with appropriate documentation. Alkermes also has patient assistance.

~2 minutes
Q2: "Is there a generic XR naltrexone?" Easy

A: No. Vivitrol is brand-only. The patent and drug delivery technology (microspheres) make generic development difficult. This is why cost remains a barrier.

~1 minute
Slide 12

Safety Considerations

4 min

Speaker Notes

  • Hepatotoxicity: black box but rare at standard doses
  • Injection site reactions: technique matters
  • Pain management blockade: critical for chronic pain patients
  • Emphasize planning ahead for pain management
⚠️ Watch for: Audience members who think naltrexone is "dangerous" for the liver. Clarify that clinically significant injury is rare at 50 mg/day; the black box is from higher doses in obesity trials.

Anticipated Questions

Q1: "How do you manage acute pain in a patient on XR naltrexone?" Hard

A: This is challenging. Options: high-dose NSAIDs, acetaminophen, ketamine (if appropriate), regional anesthesia, non-pharmacologic approaches. Opioids will be blocked. For severe pain, may need to wait for naltrexone to wear off (weeks) or use ultra-high doses with monitoring (specialist consultation required).

~3 minutes
Q2: "How often do you check LFTs?" Easy

A: Baseline, then periodically (every 3-6 months) if continued therapy. More frequently if baseline abnormalities or risk factors. Stop if ALT > 3-5x ULN.

~1 minute
Slide 13

Practical Pearls

4 min

Speaker Notes

  • Rapid-fire through these pearls
  • Each is a "clinical pearl" worth remembering
  • Pause on the buprenorphine washout — this is a common error
🎯 Key Point: The buprenorphine to naltrexone transition is high-risk. Plan the 7-14 day gap carefully — patients often relapse during this period.

Anticipated Questions

Q1: "Can you bridge with anything during the buprenorphine washout?" Hard

A: Limited options. Some use gabapentin, clonidine, or non-opioid adjuvants for comfort. The challenge is that anything with opioid activity will delay naltrexone initiation. Structured residential or intensive outpatient support is often needed.

~2 minutes
Slide 14

Knowledge Check Quiz

5 min

Speaker Notes

  • Let audience vote before revealing answer
  • Click each option to show correct/incorrect
  • Discuss rationale after reveal
🎯 Key Point: The opioid-free requirement is non-negotiable. "Close enough" isn't close enough when precipitated withdrawal is the risk.
→ Transition: "Let's summarize the key takeaways..."

Anticipated Questions

Q1: "What if the patient is in severe withdrawal at 7 days?" Hard

A: Wait longer. Withdrawal symptoms suggest residual opioid dependence. The goal is complete resolution of withdrawal before naltrexone. Consider buprenorphine induction instead if patient can't achieve opioid-free state.

~2 minutes
Slide 15

Key Takeaways

3 min

Speaker Notes

  • Read each takeaway clearly
  • Pause between each for emphasis
  • These are the "leave-behind" messages
💡 Tip: Ask audience which takeaway was most surprising or will change their practice.

Anticipated Questions

Q1: "What's the most common mistake you see?" Medium

A: Prescribing oral naltrexone for OUD and being surprised when patients don't fill the prescription or don't take it consistently. Also: rushing the opioid-free period and causing precipitated withdrawal.

~1.5 minutes
Slides 16-18

References, Discussion, Closing

7 min

Speaker Notes

  • Slide 16: Briefly show references — full citations in companion
  • Slide 17: Open for questions — use discussion prompts if needed
  • Slide 18: Thank you, mention companion materials
💡 Tip: If no questions, use the prompts on Slide 17 to spark discussion: "What's been your experience with insurance coverage?" or "How do you handle the opioid-free period?"

Anticipated Questions

Q1: "Where can I find the full XR-Open paper?" Easy

A: Lancet 2018;391(10118):309-318. Also available in the enrichment materials with critical appraisal checklist.

~30 seconds
Q2: "Do you have a patient handout for this?" Easy

A: SAMHSA has excellent patient materials on Vivitrol. The enrichment packet includes links to patient-facing resources.

~30 seconds