Late occurrence of isoniazid-induced psychosis

Dear Editor, Isoniazid (INH) is a first-line anti-tubercular drug. Psychiatric adverse reactions (ADR), including delirium, psychosis, mania, and depressive disorder have been reported with several antitubercular drugs including INH. Psychiatric ADR is usually present in the initiating phase of treatment and is rare in the continuation phase (CP) of treatment.[1] A rare case of INH-induced psychosis in a male subject in the maintenance phase of ATT for pulmonary tuberculosis is reported because of its rarity. A 26-year-old male patient, unmarried, was diagnosed with pulmonary tuberculosis in June 2023 and started on DOTS (INH 225 mg OD, Rifampicin 450 mg OD and Ethambutol 825 mg OD) therapy. He was brought to the psychiatry OPD in November 2023, in the CP of treatment with complaints of hearing voices unheard by others involving 5–6 people making fun of the patient amongst themselves, fearfulness that someone will harm him according to self, and increased irritability, decreased social interaction and muttering to self when alone by caretakers since last 10 days. Sleep was fragmented with a decreased appetite for the last 7 days. He had no past or family history of psychiatric disorders or substance abuse. Mental status examination revealed a sad mood, distressed affect, with delusions of persecution, and reference and 3rd person’s auditory hallucinations, memory and orientation were unimpaired. He lacked insight and his judgment was impaired. Routine investigations were within normal limits. Retroviral screening was seronegative. With a diagnosis of INH-induced psychosis, the patient was started on the tablet Olanzapine 5 mg HS and Isoniazid was stopped, while Rifampicin and Ethambutol were continued at the same dosage. The patient showed marked improvement in psychotic symptoms in the next 7 days. Olanzapine was tapered off over the next week and the patient did not have a relapse of psychotic symptoms even after discontinuing the drug. ATT was continued under supervision for the next few months keeping a close watch on the relapse of psychotic symptoms In the present case stopping INH and initiating an antipsychotic drug resulted in complete remission. This emphasizes the need to promptly treat the psychiatric ADR as the outcome of the latter varies greatly from complete resolution of symptoms to suicide in a few cases.[2,3] Psychiatric ADR is one of the reasons responsible for non-compliance to medication which increases disease burden as well as mortality rates. It is attributed to the fact that psychotic features significantly impact the quality of life of the patient, also posing numerous challenges to the management and care being provided to the patient by the caregivers. The caregivers must also be properly counseled in cases of neuropsychiatric ADR, paying special emphasis on adherence to medications prescribed henceforth and the possible outcomes. It has been suggested that pyridoxal-5- phosphate (produced in the body from pyridoxine) is inhibited by INH, causing a decrease in brain gamma-aminobutyric acid. INH also inhibits the monoamine oxidase enzyme. INH-induced oxidative stress causes a decrease in N-methyl D-aspartate receptors, thus resulting in the development of psychotic symptoms.[4] However, whether acute and delayed onset INH psychosis are the same or different conditions and the pathophysiology of delayed onset INH-induced psychosis remain unknown. In the present case apart from INH ethambutol has also been rarely reported to cause psychosis. However, the cessation of psychotics symptoms with stoppage of INH but a continuation of ethambutol indicates that in this case, INH was the offending agent. The present communication highlights a rare case of INH-induced psychosis of delayed onset that rapidly reversed with the stoppage of INH and the starting antipsychotic drug. Physicians should be vigilant for the occurrence of psychiatric symptoms not only in the induction phase but also in the maintenance phase of ATT. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed. Authors contribution Concept, design, literature search: AS, SC. data acquisition: AS,AH. Manuscript preparation: AS, AH. manuscript editing and manuscript review. SC, AJ. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.