# Isoniazid-Associated Serotonin Toxicity in the Critical Care Setting: A Case Report

## TL;DR

This case report highlights a rare instance of serotonin toxicity linked to isoniazid, a tuberculosis medication, in a patient with autism and severe TB.

## Contribution

The paper presents a novel clinical case linking isoniazid's MAO inhibition to serotonin toxicity despite no direct serotonergic drug use.

## Key findings

- The patient developed serotonin toxicity despite discontinuation of serotonergic psychotropics.
- Isoniazid's MAO inhibition may contribute to serotonin toxicity in vulnerable patients.
- Psychiatrists should consider pharmacodynamic interactions when prescribing drugs to patients on isoniazid.

## Abstract

Serotonin syndrome presents with the triad of neuromuscular excitability, autonomic disturbance, and altered mental status, resulting from excess serotonergic tone. Isoniazid (INH), a core agent for the management of tuberculosis (TB), is a weak, non-selective monoamine oxidase inhibitor (MAOI), and there have been minimal reports of its potential to contribute to serotonin toxicity. We present a complex case of INH-associated serotonin toxicity in a patient with autism spectrum disorder and co-occurring severe TB in the critical care setting. The patient was on rifampin, INH, pyrazinamide, and ethambutol regimen (RIPE) for pulmonary TB. Due to severe, refractory agitation for over a week, which prevented weaning of sedation and extubation, psychiatry was consulted. The psychiatry team worked to address agitation through a combination of haloperidol, lithium, valproic acid (VPA), and pregabalin. The patient developed serotonin toxicity, which persisted despite the cessation of psychotropics with serotonergic potential. This report illustrates the potential of INH’s MAO inhibition to contribute to the development of serotonin toxicity. Consulting psychiatrists should exercise caution when recommending psychotropics to patients receiving INH and should take into account pharmacodynamic and pharmacokinetic interactions associated with its use. We recommend regular screening for serotonin toxicity in patients on INH and other agents that can increase serotonergic serum levels.