A Rare Case of Isoniazid-Induced Psychosis in a Young Female

Sir, Tuberculosis is one of the most common infective diseases in the world, and even after decades of research and experience, the diagnosis and management of tuberculosis pose various challenges. The management of drug-sensitive tuberculosis includes the first-line drugs: isoniazid, rifampicin, pyrazinamide, and ethambutol which are safe and effective; however, adverse drug reactions (ADRs) are known to occur due to the complexity of the disease, prolonged treatment, and various drug interactions. Isoniazid is one of the cheapest and most potent first line drug of antitubercular therapy (ATT). It is known to cause ADRs such as peripheral neuropathy, hepatitis, and rash, but rare complications include cerebellar symptoms, psychosis, and convulsions. Herein, we present a rare case of a young female who was diagnosed with pulmonary tuberculosis and isoniazid-induced psychosis, later diagnosed with multidrug-resistant tuberculosis, which was managed at our center. A 14-year-old female was brought to our hospital with a history of altered sensorium for 5 days. There was a history of agitation, abnormal speech, and auditory hallucinations. There was no history of any previous psychiatric illness or drug abuse. She was a diagnosed case of sputum-positive pulmonary tuberculosis and was on first-line ATT (Tab isoniazid 300 mg, Tab rifampicin 450 mg, Tab pyrazinamide 1000 mg, Tab ethambutol 800 mg) for the last 5 months. She had presented 5 months ago to a civil hospital with a history of cough, fever, and weight loss for 2 months. On evaluation, she had a consolidation on the chest radiograph, and her sputum, on Zeil–Neelson staining, showed acid-fast bacilli-2+. She was diagnosed with pulmonary tuberculosis and was started on first-line ATT, however her mother gave history of poor compliance with the medications. On arrival, she was cachexic [body mass index (BMI) 16.8 kg/m2], had tachycardia, tachypnea, was hypoxic at room air, and hypotensive. Her blood investigation revealed anemia, thrombocytopenia, elevated erythrocyte Sedimation Rate (ESR) and Creactive protein (CRP) levels, raised alkaline phosphate levels with normal AST and Alanine Aminotransferase (ALT) levels, decreased serum albumin levels (1), and dyseclectrolytemia as shown in Table 1. Her chest radiograph showed multifocal consolidation in the bilateral upper and Mid zones as shown in Figure 1. Her bedside ultrasound showed a collapsing inferior vena cava with B-lines of bilateral pulmonary areas. She was managed with intravenous (IV) fluids, IV antibiotics, high-flow oxygen, and supportive management. She showed a significant response and was continued on first-line ATT. However, she remained agitated with delirious behavior and hallucinations. Her computed tomography of the head was normal. Isoniazid-induced psychosis was suspected, and isoniazid was stopped. A psychiatry consult was taken, and she was started on Tab olanzapine. Her symptoms resolved within 5 days. Her sputum, tested using Mycobacterium tuberculosis (MTB) Cartridge-Based Nucleic Acid Amplification Test (CBNAAT), showed high MTB detection with rifampicin resistance. Subsequently, her first-line probe assay showed high-level resistance to isoniazid. She was diagnosed with multidrug-resistant tuberculosis and her first-line ATT was stopped. She was started on an oral bedaquiline- based ATT and showed significant response, with clinical improvement and weight gain. She is presently on follow up. Tuberculosis is one of the commonest infectious diseases in the world, and even after decades of improvement in diagnostic and management protocols, it remains a challenge for treatment and eradication. Isoniazid is one of the most important first-line drugs in ATT. The drug is given for the entire 6 months of the treatment and is known to cause adverse effects such as hepatitis, peripheral neuropathy, and central nervous systemic effects. However, psychosis due to Isoniazid (INH) is a rare but serious side effect of the drug.[1,2] The causes of INH-induced psychosis include the destruction of the vitamin B12 complex and the inhibition of the conversion of pyridoxineto pyridoxine-5-phosphate. Pyridoxal-5-phosphate is a cofactor for glutamic acid decarboxylase, which catalyzes the conversion of glutamic acid to gamma-aminobutyric acid (GABA), causing depletion of GABA levels in the brain. This can lead to central nervous system disinhibition and seizures. INH also inhibits monoamine oxidase, leading to increased concentrations of catecholamines and serotonin. Another implicated mechanism is related to the pharmacokinetic properties of the drug. INH is rapidly metabolized and reaches its peak levels within 1 to 2 hours of ingestion. About 40% of Indians are slow acetylators, leading to reduced metabolism and increased side effects. Lack of pyridoxine supplementation has also been documented as a cause of INH-related toxicity.[2‐5] The risk factors for INH-induced psychosis include low BMI, malnutrition, old age, alcohol intake, diabetes, and Past or family history of psychiatric illness. The time of onset can range from days to months after starting the drug, with documented cases having a predilection for earlier onset. Our patient developed INH-induced psychosis 5 months after starting ATT, which has been rarely documented. Symptoms include paranoid delusions; auditory, visual, and tactile delusions; suicidality; mood symptoms; and disorientation. There can be prodromal symptoms such as headache, sleep disturbances, and twitching. The treatment strategy includes withdrawal of INH, treatment of psychosis, and a gradual reintroduction of the drug at lower dosages.[1‐3] We managed our patient with oral antipsychotic and a high dose of pyridoxine, with which she showed a significant response. Some studies have also documented that INH can be continued alongside antipsychotics, especially in cases in which the psychiatric symptoms are not very severe. Our case also highlights the importance of performing upfront MTB CBNAAT in all pulmonary cases for early diagnosis of drug resistance, preventing unnecessary complications, and avoiding delays in starting Multidrug resistance (MDR) treatment Tuberculosis is an endemic disease that needs thorough diagnostic and management protocols involving multiple drug interactions and side effects; therefore, physicians should be aware of drug toxicity profiles of antitubercular drugs to prevent and manage these complications.