Management of Naltrexone-Associated Psychosis
Naltrexone-associated psychosis should be managed by immediate discontinuation of naltrexone, followed by antipsychotic medication if symptoms persist, and consideration of alternative pharmacotherapy for the original indication.
Initial Management
- Immediate discontinuation of naltrexone is the first and most crucial step when psychosis is suspected to be medication-induced 1
- Monitor vital signs and assess for other potential causes of psychotic symptoms
- Visual hallucinations appear to be the most commonly reported psychotic symptom associated with naltrexone 1
- Document the timeline between naltrexone initiation and onset of psychotic symptoms to establish causality
Acute Symptom Management
If psychotic symptoms persist after discontinuation:
- Short-term antipsychotic medication may be necessary
- Benzodiazepines can be used as adjuncts for severe agitation
- Avoid using antipsychotics as stand-alone medications for withdrawal symptoms, as they should only be used as adjuncts to benzodiazepines in severe withdrawal delirium that has not responded to adequate doses of benzodiazepines 2
Alternative Treatment Options
After resolution of psychotic symptoms, consider alternative pharmacotherapy for the original indication:
For Alcohol Use Disorder:
- Acamprosate is a safer alternative for patients who experienced psychosis with naltrexone 2
- Disulfiram may be considered as it has shown approximate equivalence with naltrexone in effectiveness for alcohol use disorder in patients with comorbid psychosis 3
For Opioid Use Disorder:
- Buprenorphine (8-16 mg daily) is recommended as an effective approach for managing patients who cannot tolerate naltrexone 4
- For patients with chronic pain, higher doses of buprenorphine divided throughout the day may be needed 4
For Obesity Management:
- Consider alternative weight management medications such as liraglutide 3.0 mg, which works through a different mechanism (GLP-1 receptor agonist) 2
- Intensive behavioral modification should be emphasized
Risk Assessment and Monitoring
- Patients with a history of psychotic disorders are at higher risk for naltrexone-associated psychosis 3, 5
- In patients with schizophrenia, schizoaffective disorder, or bipolar disorder, careful monitoring is essential if naltrexone is used 6
- These patients had worse alcohol outcomes than those without psychotic spectrum disorders but still benefited from medication treatment compared to placebo 6
Follow-up Care
- After discontinuation of naltrexone and resolution of psychotic symptoms:
- Reassess the patient's underlying condition requiring naltrexone
- Document naltrexone-induced psychosis in the medical record as a medication allergy/adverse reaction
- Consider psychiatric consultation if symptoms persist beyond 1-2 weeks after discontinuation
- Monitor for withdrawal symptoms if naltrexone was being used for substance use disorder
Prevention Strategies
For patients requiring opioid antagonist therapy with risk factors for psychosis:
- Consider starting with lower doses of naltrexone and titrating slowly
- Implement more frequent monitoring during initiation phase
- Educate patients and caregivers about early warning signs of psychosis
- Consider alternative medications when possible for high-risk patients
Special Considerations
- In patients with comorbid psychiatric illness and substance use disorders, retention rates and medication compliance can exceed 80% with appropriate support 6
- The combination of pharmacotherapy with psychosocial interventions is essential for optimal outcomes 2
- Patients with a history of self-injurious behavior who benefited from naltrexone may require alternative treatments such as dialectical behavior therapy if naltrexone must be discontinued 7