"Adverse Drug Event "

INH Induced Psychosis in a Child – A Case Report

Abstract

One case of INH induced psychosis a relatively rare adverse drug reaction is being presented. The various mechanisms responsible for this entity are discussed with special implication on role of oxidative stress and potential usage of anti-oxidants and anti-psychotics along with pyridoxine.

Introduction
Isoniazid is a widely used anti-tubercular drug which has been extensively studied in terms of efficacy and adverse effects. The common adverse reactions with INH include peripheral neuropathy and hepatitis. All other reported reactions are rare. Other ADRs include hypersensitivity, hematological reactions, vasculitis and arthritic symptoms. The CNS adverse effects of INH though rare manifest as effects of both stimulation and depression. We present in this paper a case of INH induced psychosis in a child ¹.

Case report:
A young 10 year old female patient diagnosed with tubercular meningitis in May 2007 was put on a four drugs regimen consisting of Isoniazid (H), Rifampicin(R), Pyrazinamide (Z) and Ethambutol (E) in a blister combipack for an intensive phase of 2 months followed by continuation phase consisting of HR for 10 months. The dose of INH was 100mg (5mg/kg). After one month of medication, in June 2007, she was diagnosed with INH induced psychosis. This was reported to our ADR centre from JJ Hospital. However detailed history, use of steroids, Valproate and Phenobarbitone(which can also produce similar manifestations ) were not reported, making assessment of casuality difficult.(cause effect relationship)

Discussion
CNS stimulation due to INH manifests itself as restlessness, euphoria, insomnia and headache. CNS depression due to INH presents as mild drowsiness and somnolence ², ³. The overdose of INH leads to nausea, vomiting, dizziness, slurred speech, visual hallucination, coma, seizures, metabolic acidosis and hyperglycemia¹.

INH is metabolized by the liver enzyme N-acetyltransferase, which shows genetic polymorphism. It exists in two phenotype in population viz slow acetylators and fast acetylators. Most population in Europe and North America has 40%-70% slow acetylators while the Pacific Asian (Japanese, Chinese, Koreans and Thai) have only 10%-30% slow acetylators. Slow acetylators have higher peak levels of drug after therapeutic doses and thus higher frequency of adverse effects.

INH induced hepatitis is more common in fast acetylators while peripheral neuropathy is common in slow acetylators ⁴. Since the mechanism causing peripheral neuropathy and psychosis bears semblance, it can be speculate that INH induced psychosis would be more common in slow acetylators. However detailed studies on this are required.

Figure 1. Proposed Pathway for Isoniazid Metabolism

The mechanisms of production of neurological toxicity are not well defined. However, following are the few proposed mechanisms of psychiatric manifestations occurring with INH treatment.

AN ALGORITHM FOR MANAGING INH-INDUCED PSYCHIATRIC MANIFESTATIONS IS PROPOSED ¹¹

Mild Manifestations (Without predisposing conditions)	Severe Manifestations
INH should be continued	INH should be stopped
Treatment with Antipsychotics (Olanzepine, Risperidone)	Continue Antipsychotics (Olanzepine, Risperidone)
Pyridoxine in High Dose (50 mg/d)	Pyridoxine in High Dose (50 mg/d)
	After 1 month-start INH in low If tolerated – increase dose

Conclusion
Clinicians should be aware of INH induced psychosis. Despite the usage of pyridoxine there is occurrence of psychosis which points that in addition to pyridoxine deficiency, oxidative stress may also play role in the pathogenesis of INH induced psychosis

Note
This Adverse event has been reported to the South West zonal centre of the National Pharmacovigilance programme.The extent and completeness of information in a given report influences the quality of a case report. This case report is limited by lack of adequate information.

References
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