What is the antidote for methamphetamine and amphetamine overdose?

Antidote for Methamphetamine and Amphetamine Overdose

There is no specific antidote for methamphetamine or amphetamine overdose; treatment is entirely supportive and symptom-directed, with benzodiazepines as the cornerstone for managing the sympathomimetic toxidrome. 1, 2, 3

Immediate Management Approach

First-Line Treatment: Benzodiazepines

• Benzodiazepines are the primary pharmacologic intervention and should be administered promptly to control agitation, hypertension, tachycardia, psychosis, and seizures. 1, 2, 3
• Benzodiazepines alone may adequately relieve the entire spectrum of sympathomimetic effects without requiring additional agents. 1
• High-quality evidence (Level I studies) supports benzodiazepines for control of agitation and psychosis associated with amphetamine toxicity. 3

Second-Line Agents (When Benzodiazepines Are Insufficient)

If agitation, delirium, and movement disorders remain unresponsive to benzodiazepines, consider the following in order:

• Antipsychotics (ziprasidone or haloperidol) for persistent psychosis and severe agitation 2, 3
• Dexmedetomidine (central alpha-adrenergic agonist) for refractory agitation 2, 3
• Propofol for severe cases requiring sedation 2

Cardiovascular Management

Hypertension and Tachycardia

• Beta-blockers are recommended based on high-quality evidence (9 Level I studies) for control of hypertension and tachycardia. 3
• Calcium channel blockers are supported by 3 high-quality studies as an alternative. 3
• Alpha-blockers have Level I evidence (2 studies) and can be considered. 3
• Nitric oxide-mediated vasodilators may be used based on case report evidence. 3

Critical caveat: Benzodiazepines should be tried first for cardiovascular symptoms before escalating to specific antihypertensives, as they often resolve sympathomimetic cardiovascular effects. 1

Clinical Presentation to Anticipate

Neurological Effects

• Mydriasis, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and seizures 2

Cardiovascular Effects

• Tachycardia, hypertension, chest pain, cardiac dysrhythmias, vasculitis 1

Systemic Complications

• Hyperthermia, cerebral hemorrhage, rhabdomyolysis with renal complications, pulmonary effects, and gastrointestinal symptoms 1, 2

Mechanism of Toxicity (Informs Treatment Strategy)

• Amphetamines act as substrates for cellular monoamine transporters (particularly dopamine transporter), causing excessive release and blocking reuptake of dopamine, norepinephrine, and serotonin. 1, 2
• This results in overstimulation of central and peripheral α- and β-adrenergic postsynaptic receptors, producing the sympathomimetic toxidrome. 1

Common Pitfalls to Avoid

• Do not delay benzodiazepine administration while attempting other interventions—they are first-line for nearly all manifestations. 1, 2, 3
• Avoid using beta-blockers as first-line agents before adequate sedation with benzodiazepines, as unopposed alpha-adrenergic stimulation can theoretically worsen hypertension. 3
• Do not expect a specific reversal agent—there is no naloxone-equivalent for amphetamines; all treatment is supportive. 1, 2
• Monitor for secondary complications including rhabdomyolysis, acute kidney injury, hyperthermia, and cardiovascular events that require specific management beyond the initial sympathomimetic syndrome. 1, 2

Prognosis

• With appropriate symptom-directed supportive care, patients can be expected to make a full recovery despite severe initial presentation. 1
• Fatalities are rare with appropriate intensive care management. 2
• Most overdoses produce moderate to major morbidity requiring intensive care and prolonged hospital stays, but mortality remains low with proper treatment. 2