From the FDA Drug Label
Overdosage Signs and Symptoms Isoniazid overdosage produces signs and symptoms within 30 minutes to 3 hours after ingestion. Nausea, vomiting, dizziness, slurring of speech, blurring of vision, and visual hallucinations (including bright colors and strange designs) are among the early manifestations For the Symptomatic Patient Ensure adequate ventilation, support cardiac output, and protect the airway while treating seizures and attempting to limit absorption If the dose of isoniazid is known, the patient should be treated initially with a slow intravenous bolus of pyridoxine, over 3 to 5 minutes, on a gram per gram basis, equal to the isoniazid dose. If seizures continue, the dosage of pyridoxine may be repeated. It would be rare that more than 10 grams of pyridoxine would need to be given. If the patient does not respond to pyridoxine, diazepam may be administered.
Isoniazid-induced psychosis treatment involves:
- Pyridoxine administration: on a gram per gram basis equal to the isoniazid dose, to counteract the toxic effects of isoniazid.
- Supportive care: ensuring adequate ventilation, supporting cardiac output, and protecting the airway.
- Seizure management: using diazepam if pyridoxine is not effective. 1
From the Research
Isoniazid (INH)-induced psychosis is treated by discontinuing isoniazid and providing supportive psychiatric care, as supported by the most recent and highest quality study 2. The first step is immediate cessation of INH therapy, followed by administration of pyridoxine (vitamin B6) at doses of 100-200 mg daily to counteract the neurotoxic effects. Antipsychotic medications such as risperidone (2-4 mg daily) or olanzapine (5-10 mg daily) may be needed for symptom control during the acute phase, as reported in previous studies 3, 4. Benzodiazepines like lorazepam (1-2 mg every 4-6 hours as needed) can help manage agitation. Most patients experience symptom resolution within 2-4 weeks after INH discontinuation, as observed in a systematic review of case reports and case series 2. The underlying mechanism involves INH's interference with pyridoxine metabolism, leading to decreased GABA synthesis in the brain, which can trigger psychotic symptoms in susceptible individuals. For patients who must continue tuberculosis treatment, alternative regimens excluding isoniazid should be considered in consultation with infectious disease specialists, as suggested by a case report 5. Close monitoring for symptom improvement is essential, and psychiatric follow-up should continue until complete resolution of psychotic symptoms. Key considerations in managing INH-induced psychosis include:
- Immediate discontinuation of isoniazid
- Administration of pyridoxine to counteract neurotoxic effects
- Use of antipsychotic medications and benzodiazepines as needed for symptom control
- Alternative tuberculosis treatment regimens for patients who must continue therapy
- Close monitoring and psychiatric follow-up until symptom resolution, as emphasized by recent studies 2, 6.