Isoniazid-Induced Psychosis: Clinical Manifestations
Isoniazid-induced psychosis typically presents with delusions and/or hallucinations, often accompanied by visual hallucinations including bright colors and strange designs, with onset most commonly occurring within the first 2 months of treatment. 1, 2
Timing and Onset
- Higher frequency of psychotic symptoms occurs during the first 2 months of isoniazid therapy, with relatively early onset observed in patients aged 18 years or younger 2
- Acute presentations can manifest within 30 minutes to 3 hours after ingestion in overdose scenarios 1
- Symptoms may appear as early as 3 days after initiating treatment in susceptible individuals 3
Core Psychotic Symptoms
Primary manifestations include:
- Delusions and hallucinations are the most common presenting features 2
- Visual hallucinations with bright colors and strange designs are characteristic early manifestations 1
- Auditory hallucinations may also occur 2
Associated Neuropsychiatric Features
Beyond core psychotic symptoms, patients frequently exhibit:
- Psychomotor disturbances 2
- Disorganized speech or formal thought disorder 2
- Disorganized or abnormal behavior 2
- Sleep disturbances 2
- Hostility or aggression 2
- Confusion 2
- Affective symptoms (mood changes, depression) 2, 4
- Anxiety symptoms 2
- Cognitive difficulties 2
Early Warning Signs in Mild Cases
- Nausea and vomiting 1
- Dizziness 1
- Slurring of speech 1
- Blurring of vision 1
- Mood and behavioral changes including anorexia, apathy, and fatigue 4
Severe Presentations
In marked overdosage or severe toxicity:
- Respiratory distress 1
- CNS depression progressing from stupor to profound coma 1
- Severe, intractable seizures 1
- Severe metabolic acidosis 1
Critical Clinical Pearls
Key distinguishing features:
- Awareness and level of consciousness typically remain intact in isoniazid-induced psychosis (unlike delirium), unless severe overdose has occurred 5
- More than 80% of cases rechallenged with isoniazid resulted in recurrence of psychotic symptoms, confirming the causal relationship 2
- The presentation can be acute and intense in patients without prior psychiatric history 6, 3
Risk Factors for Development
Predisposing factors include:
- Slow acetylator status 7
- Diabetes mellitus 4, 7
- Hepatic insufficiency 7
- Advanced age 7
- Alcoholism 4, 7
- Family or personal history of mental illness 7
- Nutritional deficiency states 4
Mechanism and Pathophysiology
Two primary mechanisms explain the presentation:
- Pyridoxine (vitamin B6) deficiency leading to decreased neurotransmitter synthesis, particularly serotonin 4, 7, 6
- Direct isoniazid toxicity related to its chemical similarity to iproniazid, a powerful monoamine oxidase inhibitor 7