What is the recommended dose of pyridoxine (Vitamin B6) for isoniazid-induced psychosis?

Pyridoxine Dosing for Isoniazid-Induced Psychosis

For isoniazid-induced psychosis (not acute overdose), administer pyridoxine 50-100 mg orally daily, as this condition results from chronic pyridoxine depletion rather than acute toxicity requiring gram-for-gram replacement. 1

Distinguishing Psychosis from Acute Overdose

The dosing strategy for pyridoxine depends critically on whether you're treating chronic isoniazid-induced psychosis versus acute isoniazid overdose with seizures:

Chronic Isoniazid-Induced Psychosis

• Psychosis from therapeutic isoniazid use is caused by gradual pyridoxine (vitamin B6) deficiency, occurring in 1-2% of patients on chronic therapy 2
• The mechanism involves pyridoxine depletion leading to decreased GABA synthesis and potential monoamine oxidase inhibition effects 3
• Treatment requires standard vitamin B6 replacement doses of 50-100 mg orally daily for one to two weeks 1
• This is the same dosing used for any chronic vitamin B6 deficiency from poor dietary intake or medication-induced depletion 1
• After resolution, continue pyridoxine supplementation at 10-100 mg daily throughout isoniazid therapy to prevent recurrence 1

Acute Isoniazid Overdose (Different Scenario)

• In contrast, acute isoniazid overdose with seizures requires massive pyridoxine doses: 1 gram of pyridoxine IV for each gram of isoniazid ingested, up to 5 grams maximum 4
• If the ingested amount is unknown, give 5 grams IV in adults or 80 mg/kg in children 4, 5
• This gram-for-gram replacement is necessary because acute overdose causes immediate GABA depletion and refractory seizures 6

Clinical Approach to Psychosis

When encountering isoniazid-induced psychosis specifically:

• Discontinue isoniazid immediately and initiate pyridoxine 50-100 mg daily 1, 3
• The favorable evolution after stopping isoniazid with pyridoxine supplementation confirms the diagnosis 3
• Predisposing factors include slow acetylator status, diabetes, hepatic insufficiency, advanced age, alcoholism, and personal/family psychiatric history 3
• Resolution typically occurs within days to weeks of stopping isoniazid and starting pyridoxine replacement 3, 2

Prevention Strategy

Systematic pyridoxine supplementation (10-100 mg daily) should be given prophylactically to all patients receiving isoniazid therapy to prevent neuropsychiatric complications 1, 3

Safety Considerations

• Avoid prolonged doses exceeding 300 mg/day due to neurotoxicity risk, including sensory neuropathy and Lhermitte signs 1
• Long-term doses as low as 100 mg/day have been associated with spinal cord effects 1
• The 50-100 mg daily range for treating psychosis is well below the neurotoxicity threshold 1

Common Pitfall

Do not confuse the dosing for chronic isoniazid-induced psychosis (50-100 mg daily) with acute isoniazid overdose seizures (gram-for-gram replacement). The case report of inadequate pyridoxine therapy leading to status epilepticus involved acute overdose, not chronic psychosis 5. Using overdose protocols for psychosis would be excessive and potentially harmful, while using deficiency replacement doses for acute overdose would be dangerously inadequate 5, 7.