What is the presentation and treatment of an amphetamine overdose, and does it differ by type of amphetamine?

Amphetamine Overdose: Presentation and Treatment

Clinical Presentation

Amphetamine overdose presents as a sympathomimetic toxidrome characterized by cardiovascular and CNS hyperactivity, with the core presentation being similar across amphetamine types (including methamphetamine, dextroamphetamine, and mixed amphetamine salts like Adderall), though severity and specific complications may vary. 1

Common Clinical Features Across All Amphetamine Types

The overdose syndrome is characterized by excessive extracellular dopamine, norepinephrine, and serotonin, producing:

Cardiovascular Effects:

• Tachycardia and tachyarrhythmias 1, 2
• Hypertension (or paradoxically hypotension in severe cases) 1
• Risk of vasospasm, myocardial infarction, aortic dissection, and sudden cardiac death 1
• Takotsubo cardiomyopathy may develop 1

Neurological Effects:

• Psychomotor agitation, confusion, and hallucinations 1, 2
• Mydriasis, tremor, hyperreflexia 2, 3
• Combative behavior, delirium, anxiety, paranoia 2
• Movement disorders and seizures 2
• Serotonin syndrome may occur 1
• Cerebral vascular accidents and coma in severe cases 1

Life-Threatening Complications:

• Hyperthermia (temperatures >104°F) 1, 3
• Rhabdomyolysis 1
• Posterior reversible encephalopathy syndrome (PRES) in severe hypertensive cases 4

Differences by Amphetamine Type

Methamphetamine vs. Prescription Amphetamines:

• The clinical presentation is fundamentally similar across types, as all work through the same mechanism of inhibiting dopamine and norepinephrine transporters 5
• Methamphetamine may have higher abuse potential and more severe presentations due to typical higher doses used illicitly 1
• Extended-release formulations (like Adderall XR) may cause delayed onset of peak symptoms, with effects potentially appearing 9-14 hours post-ingestion 4

"Overamping" Phenomenon:

• People who use methamphetamine describe a constellation of psychological and physical symptoms on a continuum from less to more severe, which they term "overamping" 6
• Acute fatal methamphetamine overdose is reported as rare by users, though severe morbidity is common 6

Treatment Approach

The management of amphetamine overdose is primarily supportive, focusing on aggressive sedation with benzodiazepines as first-line therapy, followed by antipsychotics or dexmedetomidine for refractory agitation, and careful cardiovascular management avoiding beta-blockers alone. 7, 2

Immediate Management Algorithm

Step 1: Stabilization and Decontamination

• Consider multiple drug ingestion 1
• D-amphetamine is not dialyzable 1
• Contact Poison Help line (1-800-222-1222) or medical toxicologist for complex cases 1

Step 2: Control Agitation and Psychosis (First Priority)

First-Line: Benzodiazepines

• Use benzodiazepines as primary therapy for agitation, psychosis, and interruption of sympathomimetic syndrome 7, 2
• High-quality evidence (6 studies) supports this approach 7
• Titrate to effect for sedation control 2

Second-Line (for benzodiazepine-refractory cases):

• Antipsychotics: Ziprasidone or haloperidol 2
  • High-quality evidence supports butyrophenone and later-generation antipsychotics 7
  • Phenothiazines can also control seizures 3
• Dexmedetomidine: Central alpha-adrenoreceptor agonist 2
  • Several case reports detail successful use 7
• Propofol: For severe refractory cases 2

Step 3: Cardiovascular Management

For Tachycardia and Hypertension:

• Beta-blockers: High-quality evidence (9 studies) supports safety and efficacy for controlling hypertension and tachycardia 7
  • Propranolol can manage cardiac tachyarrhythmias 3
  • Critical caveat: Avoid beta-blockers in isolation for severe vasoconstriction as they may worsen symptoms through unopposed alpha-adrenergic stimulation 8

For Severe Hypertension/Hypertensive Emergency:

• Alpha-blockers (phentolamine): Effective for severe vasoconstriction and hypertensive emergencies 8, 4
  • Two level I studies support use 7
  • Successfully used in PRES cases 4
• Calcium channel blockers (nicardipine): Three high-quality studies support use 7
  • Particularly useful for improving ocular blood flow in vasoconstriction 8
  • Can be initiated after phentolamine for sustained control 4

Step 4: Supportive Care

Temperature Management:

• Aggressive cooling for hyperthermia >104°F 1, 3
• Intravenous fluids to counter hyperthermia 3

Renal Protection:

• IV fluids to maintain renal function and promote amphetamine elimination 3
• Monitor for rhabdomyolysis and treat accordingly 1

Seizure Control:

• Benzodiazepines first-line 2, 3
• Phenothiazines, pentobarbital, or propofol for refractory seizures 3

Special Considerations and Pitfalls

Extended-Release Formulations:

• Symptoms may be delayed 9-14 hours post-ingestion 4
• Prolonged monitoring required (minimum 24-36 hours) 4
• Peak effects may occur much later than immediate-release preparations 4

Mixed Ingestions:

• Co-ingestion with clonidine can cause initial hypertension followed by hypotension and bradycardia, complicating management 4
• Always consider polypharmacy 1

Cardiovascular Complications:

• Monitor for vasospasm-related complications including visual hypoperfusion, myocardial infarction, and aortic dissection 8, 1
• Patients with pre-existing cardiovascular conditions are at higher risk 8
• Avoid concurrent vasoconstrictive substances (caffeine, decongestants) 8

Warning Signs Requiring Intensive Intervention:

• Severe headache with visual symptoms (possible cerebrovascular effects) 8
• Persistent visual changes despite treatment 8
• Severe hypertension or tachycardia indicating systemic sympathetic overstimulation 8
• Temperature >104°F 1

Monitoring Parameters

• Vital signs frequently, particularly blood pressure and heart rate 8
• Core temperature 1, 3
• Cardiac rhythm monitoring 1, 3
• Renal function and creatine kinase for rhabdomyolysis 1
• Consider ophthalmological evaluation for visual symptoms 8

Prognosis

Prognosis depends on severity and duration of clinical signs at presentation 3. With appropriate aggressive supportive care, fatalities are rare despite major morbidity requiring intensive care and prolonged hospitalization 2.