Characteristics of isoniazid-induced psychosis: a systematic review of case reports and case series

Abstract

Purpose: Isoniazid, a first-line antitubercular drug, is associated with nervous system adverse drug reactions such as seizures, peripheral neuropathy, and psychosis. This systematic review of case reports and case series aimed to characterize the demographic, social, and clinical factors associated with isoniazid-induced psychosis in patients with active tuberculosis (TB) and those who received isoniazid for latent TB infection (LTBI).

Methods: We comprehensively searched the Embase, PubMed, and Scopus databases to identify relevant studies published between the date of inception of the database and June 2024.

Results: A total of 28 studies, including 21 case reports and 7 case series involved 37 patients who developed isoniazid-induced psychosis. A higher frequency of isoniazid-induced psychosis was observed during the first 2 months of treatment, with a relatively early onset observed among patients aged 18 years or less. Delusions and/or hallucinations are the common symptoms of isoniazid-induced psychosis. Psychomotor disturbances, disorganized speech or formal thought disorder, disorganized or abnormal behaviour, and neuropsychiatric symptoms (sleep disturbances, hostility or aggression, confusion, affective symptoms, anxiety symptoms, and cognitive difficulties) were the other symptoms observed in the included studies. More than 80% of cases rechallenged with isoniazid resulted in the recurrence of psychotic symptoms.

Conclusion: Patients with TB and LTBI should be assessed for psychotic and neuropsychiatric symptoms during isoniazid therapy, mainly in the first 2 months. Further research is required to understand the impact of underlying risk factors, such as genetic predisposition and isoniazid pharmacokinetics, as well as the clinical utility and dosage recommendations of pyridoxine for managing isoniazid-induced psychosis.

Keywords: Adverse drug reaction; Isoniazid; Psychosis; Pyridoxine; Tuberculosis.

Fig. 1

PRISMA 2020 flow diagram for study selection. Abbreviations: INH, isoniazid; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; TB, tuberculosis

Fig. 2

Medication, family and social history profile of patients who developed psychosis after the administration of isoniazid. *Cases that were not isoniazid induced psychosis has been excluded from the case series. Pyridoxine administered before the occurrence of the psychosis. Abbreviations: Fam_hist_Psy_illness, family history of psychiatric illness; NR, not reported; PAS, para-aminosalicylic acid

Fig. 3

Onset of psychosis symptoms with a dose of isoniazid. Footnote: Out of the 37 observed cases, only 21 were included in this study, while the remaining 16 were excluded due to incomplete documentation of dose or onset of psychosis. Abbreviation: mg, milligram