Stimulant Toxicity: Symptoms and Treatment
Stimulant toxicity presents primarily with sympathomimetic syndrome characterized by neurological and cardiovascular manifestations, requiring immediate supportive care with benzodiazepines as first-line treatment for agitation and seizures. 1
Clinical Presentation of Stimulant Toxicity
Neurological Symptoms
- Agitation, combative behavior, and delirium are hallmark features of stimulant overdose 1
- Paranoid hallucinations and psychotic symptoms can occur, with documented cases at single doses of 300 mg amphetamine in normal adults 2
- Seizures, tremor, hyperreflexia, and movement disorders represent severe CNS toxicity 1
- Mydriasis (dilated pupils), confusion, and anxiety are common presenting signs 1
Cardiovascular Manifestations
- Hypertension and tachyarrhythmias dominate the cardiovascular presentation 1
- Severe hypertension can lead to hypertensive encephalopathy or intracerebral hemorrhage, particularly with phenylpropanolamine where toxicity occurs at less than three times therapeutic dose 3
- Cardiovascular damage is a documented risk with extremely high doses (50 times therapeutic levels) 2
Secondary Complications
- Rhabdomyolysis occurs in 30.5% of amphetamine toxicity cases 4
- Hyperthermia and dehydration require immediate attention 4
- Renal, muscle, pulmonary, and gastrointestinal effects may develop as secondary complications 1
Treatment Algorithm
First-Line Management
Benzodiazepines are the cornerstone of acute stimulant toxicity treatment, effectively managing 70-90% of agitated patients 4. The approach is:
- Administer benzodiazepines immediately for agitation, seizures, and sympathomimetic symptoms 1, 4
- Provide supportive care focusing on interruption of the sympathomimetic syndrome 1
- Control hypertension with rapidly acting vasodilators when present 3
- Treat tachyarrhythmias with beta-blockers as needed 3
Second-Line Therapies
When benzodiazepines fail to control agitation, delirium, or movement disorders 1:
- Antipsychotics: ziprasidone or haloperidol 1
- Central alpha-adrenergic agonists: dexmedetomidine 1
- Propofol for refractory cases 1
Critical caveat: Avoid high-potency first-generation antipsychotics in acute stimulant intoxication as they may precipitate malignant catatonia 5. Use antipsychotics judiciously only when benzodiazepines fail.
Supportive Measures
- De-escalating communication and stimulus shielding are essential environmental interventions 4
- Treat hyperthermia and dehydration aggressively 4
- Monitor for rhabdomyolysis with serial creatine kinase levels 4
Dose-Dependent Toxicity Considerations
The evidence distinguishes between therapeutic and toxic exposures:
- Therapeutic doses in ADHD treatment (0.3 mg/kg orally in children) rarely cause serious toxicity 2
- Severe toxicity occurs at doses 50 times therapeutic levels, as documented in Japanese factory workers taking large amphetamine amounts 2
- The NIH Consensus Development Conference cautioned that extremely high doses cause CNS damage, cardiovascular damage, and hypertension 2
Common Pitfalls to Avoid
- Do not use plasma levels to guide treatment - methylphenidate plasma levels do not correlate with clinical response or toxicity 2
- Avoid aggressive antipsychotic use before adequate benzodiazepine trials, as this increases risk of malignant catatonia 5
- Do not overlook secondary complications like rhabdomyolysis and hyperthermia, which require specific interventions 4
- Recognize that confusion may worsen in delirious patients given stimulants therapeutically 6
Prognosis
Overdose with ADHD medications produces major morbidity requiring intensive care and prolonged hospitalization, but fatalities are rare with appropriate care 1. The key to favorable outcomes is early recognition and aggressive supportive management with benzodiazepines as the primary intervention.