What is the treatment for acute psychosis from Wilson’s disease?

Treatment of Acute Psychosis from Wilson's Disease

Initial treatment for acute psychosis in Wilson's disease should include a chelating agent (penicillamine or trientine) to address the underlying copper toxicity causing the psychiatric symptoms. 1

Primary Treatment Approach

Copper Chelation Therapy

• D-Penicillamine or trientine should be started immediately as the first-line treatment for symptomatic patients with Wilson's disease presenting with psychosis 1
• These medications promote urinary excretion of copper, addressing the root cause of neuropsychiatric symptoms 1
• Chelation therapy alone can improve psychotic symptoms as copper levels decrease, potentially without requiring antipsychotic medications 2
• Initial dosing should be carefully monitored as neurological symptoms (including psychiatric manifestations) may worsen in 10-50% of patients during the early phase of chelation treatment 1

Alternative Chelating Agent

• Tetrathiomolybdate is an experimental chelating agent that may be preferable for patients with neuropsychiatric symptoms as it appears less likely to cause neurological deterioration during initial treatment 1
• This medication remains experimental in the United States and is not commercially available 1

Adjunctive Treatments

Antipsychotic Considerations

• If antipsychotic medications are needed for symptom control, they should be used cautiously due to the risk of worsening extrapyramidal symptoms in Wilson's disease 3, 4
• Atypical antipsychotics are preferred over typical antipsychotics due to lower risk of extrapyramidal side effects 1, 4
• Low doses should be used initially (e.g., risperidone 2 mg/day or olanzapine 7.5-10 mg/day) 1
• Careful monitoring is essential as patients with Wilson's disease may develop abnormal involuntary movements that could be misinterpreted as medication side effects rather than disease manifestations 5

Supportive Measures

• Antioxidants, particularly vitamin E, may have a role as adjunctive treatment as serum and hepatic vitamin E levels are often low in Wilson's disease 1
• Dietary modifications to reduce copper intake (avoiding shellfish, nuts, chocolate, mushrooms, and organ meats) should be implemented, especially during the first year of treatment 1
• Consultation with a dietitian is advisable, particularly for vegetarians 1

Monitoring and Follow-up

• Frequent monitoring is essential during the initial phase of treatment 1
• Laboratory testing should include liver biochemistries, tests of hepatic synthetic function, and indices of copper metabolism (serum copper and ceruloplasmin) 1
• 24-hour urinary copper excretion should be monitored to assess treatment efficacy and compliance 1
• Target values for patients on chelation therapy should be 200-500 μg/day (3-8 μmol/day) 1
• Physical examinations should look for evidence of liver disease and neurological symptoms 1
• Psychiatric symptoms, especially depression, should be carefully monitored 1

Special Considerations

• Treatment must never be terminated indefinitely, even if symptoms resolve 1
• Interruption of treatment has resulted in fulminant hepatic failure and severe neuropsychiatric deterioration 1
• For patients with decompensated liver disease alongside psychosis, a combined regimen of chelator and zinc may be necessary, with careful timing to avoid interaction between medications 1
• Liver transplantation may be considered for patients with severe neuropsychiatric disease that doesn't respond to medical therapy, though outcomes are variable 1

Long-term Management

• After adequate treatment with a chelator (typically 1-5 years), stable patients may be transitioned to zinc maintenance therapy 1
• Zinc is more selective for removing copper than penicillamine or trientine and is associated with fewer side effects 1
• Psychoeducation and supportive psychotherapy have been shown to improve medication adherence, which is critical for long-term management 4