What are the risks of stopping Vivitrol (naltrexone) for opioid dependence?

Risks of Stopping Vivitrol (Naltrexone) for Opioid Dependence

The most critical risk of stopping Vivitrol is a dramatically increased risk of fatal opioid overdose due to loss of opioid tolerance, which can occur rapidly after discontinuation. 1, 2

Primary Mortality Risk: Overdose

Patients who discontinue naltrexone treatment have increased risk of opioid overdose and death due to decreased opioid tolerance. 1 This represents the single most important clinical concern when stopping Vivitrol:

• During the treatment period with extended-release naltrexone, opioid receptors are continuously blocked, preventing tolerance development 3
• Once Vivitrol is discontinued, patients may mistakenly believe they can use their previous opioid dose, not recognizing their tolerance has been reset to near-zero 1
• In one criminal justice study, there were zero overdose events in the extended-release naltrexone group during treatment, but seven overdoses occurred in the usual-treatment group over 78 weeks of observation 4

Relapse Risk and Timeline

Opioid-use prevention effects wane rapidly after Vivitrol discontinuation, with relapse rates equalizing between treated and untreated groups within approximately one year. 4

• During the 24-week treatment phase with extended-release naltrexone, participants had significantly longer median time to relapse (10.5 vs. 5.0 weeks) and lower relapse rates (43% vs. 64%) compared to usual treatment 4
• However, at week 78 (approximately 1 year after treatment ended), rates of opioid-negative urine samples were equal between groups (46% in each), indicating complete loss of protective effect 4
• The protective effects of naltrexone exist only while the medication is active in the system 4

Neurobiological Considerations

The underlying neurobiological changes of opioid addiction persist for years after drug discontinuation, making addiction a chronic brain disease requiring continuous care. 5

• Brain circuit changes involving reward, conditioning, self-regulation, and stress reactivity persist even years after opioid discontinuation 5
• These persistent neuroadaptations explain why addiction treatment requires continuous care rather than time-limited intervention 5
• Medications for opioid use disorder (methadone, buprenorphine, and naltrexone) significantly improve outcomes by reducing relapse, preventing overdoses, and preventing HIV transmission 5

Withdrawal from Naltrexone Itself

Unlike opioid agonists, naltrexone discontinuation does not cause physical withdrawal symptoms because it is an antagonist, not an agonist. 5

• Physical dependence and withdrawal occur with opioid agonists (morphine, heroin, oxycodone) but not with opioid antagonists like naltrexone 5
• However, discontinuation of long-term naltrexone therapy has been associated with adverse events including mental health crises, requiring close monitoring during any planned discontinuation 1

Psychiatric Risks

Depression, suicidal ideation, and suicide attempts have been reported in patients with opioid dependence, though no causal relationship with naltrexone has been established. 2, 6

• In alcoholism treatment trials, depression rates ranged from 0-15% with naltrexone versus 0-17% with placebo, and suicide attempt/ideation rates were 0-1% with naltrexone versus 0-3% with placebo 6
• These psychiatric symptoms reflect the underlying addiction disorder rather than naltrexone effects, but patients remain vulnerable after discontinuation 2
• Families and caregivers should monitor for emergence of depression or suicidality after naltrexone discontinuation 2

Critical Safety Recommendations

Provide opioid overdose education and naloxone to all patients discontinuing Vivitrol. 1

• Patients must understand their opioid tolerance has been reset and previous doses could be fatal 1
• Naloxone (Narcan) should be prescribed and administration training provided before discontinuation 1
• Close follow-up (at least monthly) is essential during the transition period 1

Alternative Treatment Considerations

Rather than stopping medication-assisted treatment entirely, consider transitioning to buprenorphine or methadone, which provide continuous opioid receptor engagement and superior retention rates. 5, 1

• Methadone and buprenorphine are first-line treatments for opioid use disorder with stronger evidence for preventing relapse compared to naltrexone 1
• These medications should not be reduced or discontinued in attempts to comply with dose guidelines, as most patients relapse to more dangerous opioids 5
• Buprenorphine has both analgesic properties and effectiveness for opioid use disorder, making it suitable for patients with co-occurring pain 7

Common Clinical Pitfall

The most dangerous pitfall is failing to prepare patients for the dramatically increased overdose risk if they return to opioid use after Vivitrol discontinuation. 1 This education must be explicit, documented, and reinforced with family members who can intervene in crisis situations.