Can You Overdose on Vyvanse?

Yes, overdose on Vyvanse (lisdexamfetamine) is absolutely possible and can result in life-threatening toxicity and death. 1

Overdose Risk and Severity

Misuse and abuse of CNS stimulants, including lisdexamfetamine, can result in overdose and death, with this risk increased at higher doses or with unapproved methods of administration such as snorting or injection. 1
The FDA explicitly warns that overdose of CNS stimulants is characterized by sympathomimetic effects including tachyarrhythmias, hypertension or hypotension, vasospasm, myocardial infarction, aortic dissection, and sudden cardiac death. 1
Life-threatening complications include temperatures greater than 104°F, rhabdomyolysis, serotonin syndrome, seizures, cerebral vascular accidents, and coma. 1

Cardiovascular manifestations:

Tachyarrhythmias, hypertension or hypotension 1
Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death 1
Takotsubo cardiomyopathy may develop 1

Central nervous system effects:

Psychomotor agitation, confusion, and hallucinations 1
Mydriasis, tremor, hyperreflexia, combative behavior, delirium, anxiety, paranoia 2
Seizures, cerebral vascular accidents, and coma 1
Movement disorders 2

Secondary complications:

Hyperhidrosis, excessive thirst, and polydipsia leading to severe hyponatremia and water intoxication 3
Serotonin syndrome when combined with other serotonergic agents 1, 4
Life-threatening hyperthermia and rhabdomyolysis 1

A 6-year-old girl who accidentally ingested lisdexamfetamine developed serotonin syndrome with persistent neuromuscular hyperactivity and severe agitation requiring dexmedetomidine after benzodiazepines failed. 4
An 8-year-old boy who mistakenly took methylphenidate (a related stimulant) instead of his prescribed lisdexamfetamine developed hyperhidrosis, polydipsia, hypothermia, severe hyponatremia, and status epilepticus requiring intubation. 3
US poison centers reported 17,000 human exposures to ADHD medications in 2010, with 80% occurring in children under 19 years old. 2

First-line interventions:

Contact the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations. 1
Consider the possibility of multiple drug ingestion, as overdose with multiple drugs is common. 5
Establish standard airway management, support of breathing, and treatment of hypotension and dysrhythmias. 5

Pharmacologic management:

Judicious use of benzodiazepines is the primary treatment for interrupting the sympathomimetic syndrome, focusing on sedation and control of agitation. 2
For agitation, delirium, and movement disorders unresponsive to benzodiazepines, second-line therapies include antipsychotics (ziprasidone or haloperidol), central alpha-adrenoreceptor agonists (dexmedetomidine), or propofol. 2, 4

Important limitations:

Lisdexamfetamine and d-amphetamine are not dialyzable. 1
The pharmacokinetic profile of lisdexamfetamine should be considered when treating overdose patients, as it is a prodrug that is converted to dextroamphetamine. 1

Do not underestimate the severity of stimulant overdose—while fatalities are rare with appropriate care, major morbidity is common, with many cases requiring intensive care medicine and prolonged hospital stays. 2
Be aware that some children show paradoxical reactions to benzodiazepines, necessitating alternative sedation strategies like dexmedetomidine. 4
Monitor for secondary complications including severe hyponatremia from polydipsia, which can lead to seizures and require treatment with 3% NaCl saline solution. 3
Recognize that the combination of benzodiazepines with high-dose antipsychotics to manage amphetamine-induced agitation carries a risk of oversedation and respiratory depression. 6