What is the frequency of naltrexone-induced psychosis?

Frequency of Naltrexone-Induced Psychosis

Naltrexone-induced psychosis is a rare adverse effect with limited documentation in the medical literature, with only isolated case reports suggesting its occurrence.

Overview of Naltrexone

Naltrexone is an opioid antagonist primarily used for:

• Treatment of alcohol use disorders
• Treatment of opioid use disorders
• Component in combination medications for obesity (naltrexone/bupropion)

Incidence of Psychosis with Naltrexone

The available evidence does not provide specific frequency data on naltrexone-induced psychosis. None of the major guidelines or drug information sources explicitly quantify this adverse effect, suggesting it is extremely rare. The American Family Physician guidelines on substance misuse do not list psychosis among the common or serious adverse effects of naltrexone 1.

What We Know:

• Naltrexone's common adverse effects include:

  • Hepatic injury at supratherapeutic doses (requiring liver function monitoring)
  • Nausea
  • Headache
  • Dizziness
  • Fatigue
  • Insomnia
  • Anxiety

• Serious adverse effects documented in guidelines include:

  • Precipitation of opioid withdrawal in patients currently taking opioids
  • Blocking of pain relief from opioid analgesics
  • Hepatotoxicity at high doses

Evidence in Special Populations

Patients with Schizophrenia and Related Disorders

Interestingly, naltrexone has been studied in patients with schizophrenia spectrum disorders with alcohol use problems without reports of worsening psychosis in most studies:

• A 2007 study of monitored naltrexone in 19 subjects with schizophrenia spectrum and alcohol use disorders showed significant reductions in PANSS positive, negative, and general psychopathology scores, suggesting improvement rather than worsening of psychotic symptoms 2.

• A 2017 systematic review of naltrexone for alcohol use disorder in individuals with comorbid psychosis endorsed naltrexone as both safe and effective in this population 3.

• A 2000 study of 72 mentally ill patients (including 17 with schizophrenia) treated with naltrexone for alcohol use disorders found good clinical response with only 11.1% discontinuing due to side effects (primarily nausea), with no mention of psychosis as an adverse effect 4.

Case Report of Visual Hallucinations

The only direct evidence of psychotic symptoms comes from a 2019 case report describing naltrexone-associated visual hallucinations 5. This report specifically notes that "potential psychotic symptoms due to adverse effects of naltrexone have not been investigated" in patients with schizophrenia, suggesting the rarity of this adverse effect.

Clinical Implications

When prescribing naltrexone:

1. Be aware that psychosis is a possible but extremely rare adverse effect
2. Monitor patients for any new or worsening psychiatric symptoms
3. Consider that patients with pre-existing psychotic disorders have generally tolerated naltrexone well in clinical studies
4. Weigh the benefits of naltrexone against this rare risk, particularly in patients with:
   • History of psychosis
   • Family history of psychotic disorders
   • Current use of medications that might increase psychosis risk

Monitoring Recommendations

For patients on naltrexone:

• Monitor liver function tests at baseline and every 3-6 months 1
• Assess for neuropsychiatric symptoms at follow-up visits
• Educate patients and families about reporting unusual mental status changes

Conclusion

While naltrexone-induced psychosis appears to be extremely rare based on the available evidence, clinicians should remain vigilant for this potential adverse effect, particularly when initiating treatment or increasing dosage. The benefit-risk profile of naltrexone remains favorable for its approved indications, even in patients with pre-existing psychotic disorders.