What is the treatment for isoniazid-induced psychosis?

Treatment of Isoniazid-Induced Psychosis

Immediately discontinue isoniazid and administer pyridoxine (vitamin B6) supplementation, as pyridoxine deficiency is the primary mechanism underlying isoniazid-induced psychosis. 1, 2

Immediate Management

Discontinue Isoniazid

• Stop isoniazid therapy immediately upon recognition of psychotic symptoms. 3, 4
• Do not rechallenge with isoniazid, as more than 80% of patients rechallenged experienced recurrence of psychotic symptoms. 5
• Psychotic symptoms typically resolve partially or completely after isoniazid discontinuation. 3

Pyridoxine Administration

• Administer pyridoxine (vitamin B6) supplementation as the primary treatment intervention. 1, 2
• Pyridoxine deficiency is the key pathogenic mechanism, as isoniazid inhibits pyridoxine-dependent enzymes and depletes vitamin B6 stores. 1, 3
• The specific dosing of pyridoxine for treating established psychosis is not well-defined in the literature, but supplementation should be initiated promptly. 2

Pharmacological Management of Persistent Symptoms

Antipsychotic Therapy

• If psychotic symptoms persist after isoniazid discontinuation and pyridoxine supplementation, initiate treatment with an atypical antipsychotic. 3
• Start with risperidone 2 mg/day or olanzapine 7.5-10 mg/day as first-line agents due to better tolerability and lower extrapyramidal side effects. 6
• In the reported case by Levine and Rosenblatt, olanzapine successfully resolved persistent psychotic symptoms after isoniazid discontinuation. 3
• Monitor response over 4-6 weeks before considering medication changes. 6

Adjunctive Benzodiazepines

• Consider short-term benzodiazepines as adjuncts to help stabilize acute agitation or severe anxiety, though use caution with long-term administration. 6

Clinical Presentation and Timeline

Symptom Recognition

• Delusions and/or hallucinations are the most common presenting symptoms. 5
• Additional manifestations include psychomotor disturbances, disorganized speech, abnormal behavior, sleep disturbances, hostility, confusion, and cognitive difficulties. 5
• Visual hallucinations (including bright colors and strange designs) may occur as part of the clinical picture. 7

Temporal Pattern

• Psychotic symptoms most frequently develop within the first 2 months of isoniazid treatment. 5
• Onset may be particularly early in patients aged 18 years or younger. 5
• Symptoms typically manifest within 30 minutes to 3 hours in acute overdose situations. 7

Tuberculosis Treatment Continuation

Alternative Anti-TB Regimen

• Substitute rifampin-based regimens without isoniazid for continued tuberculosis treatment. 8
• Four months of daily rifampin is a preferred alternative regimen with high effectiveness and safety. 8
• Three months of daily rifampin plus ethambutamol can be considered as an alternative continuation phase. 8

Prevention Strategies

Prophylactic Pyridoxine

• Routine pyridoxine supplementation during isoniazid therapy should be systematic to prevent neuropsychiatric complications. 1
• This is particularly important in high-risk populations including slow acetylators, diabetics, patients with hepatic insufficiency, elderly patients, and those with alcohol use disorder. 1

Risk Factor Assessment

• Identify patients with family or personal history of mental illness, as these are predisposing factors for isoniazid-induced psychosis. 1
• Monitor all patients receiving isoniazid for psychotic and neuropsychiatric symptoms, especially during the first 2 months of therapy. 5

Common Pitfalls to Avoid

• Do not continue isoniazid after psychotic symptoms emerge, as this will perpetuate the adverse reaction. 3, 4
• Do not attempt rechallenge with isoniazid, given the high recurrence rate of psychotic symptoms. 5
• Do not delay pyridoxine supplementation while waiting for psychiatric consultation or antipsychotic initiation. 2
• Do not assume psychosis is due to underlying psychiatric illness without first considering medication-induced etiology in patients on isoniazid. 1, 3
• Do not overlook the need for alternative tuberculosis treatment, as discontinuing isoniazid requires substitution with effective anti-TB therapy to prevent treatment failure. 8