What are the risks associated with dextroamphetamine (amphetamine)

Risks of Dextroamphetamine

Dextroamphetamine carries a high potential for abuse and dependence (FDA Schedule II controlled substance with black box warning), along with significant cardiovascular risks including increased blood pressure, heart rate, and potential for sudden cardiac death in patients with underlying heart disease. 1

Critical Safety Warnings

Abuse, Misuse, and Addiction Risk

• Dextroamphetamine has a high potential for abuse and misuse that can lead to substance use disorder and addiction, as emphasized by FDA black box warnings 1
• Misuse and abuse can result in overdose and death, with risk increasing substantially with higher doses or unapproved administration methods (snorting, injection) 1
• The medication can be diverted for non-medical use into illicit channels 1
• Prolonged administration may lead to dependence 2

Cardiovascular Risks

Sudden Cardiac Death:

• Sudden death has been reported in patients with structural cardiac abnormalities or serious cardiac disease treated at recommended ADHD dosages 1
• Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease 1
• Prolonged amphetamine use has been associated with cardiomyopathy, characterized by left ventricular hypertrophy, dilation, or systolic dysfunction 3

Blood Pressure and Heart Rate Elevations:

• Dextroamphetamine increases systolic blood pressure by approximately 2-4 mmHg and diastolic blood pressure by similar amounts 1, 4
• Heart rate increases by approximately 3-6 bpm (mean increase 3.71 bpm) 1, 4
• These cardiovascular effects are sustained with long-term use (≥8 weeks), suggesting persistent increased risk of adverse cardiovascular events 4
• All patients require monitoring for potential tachycardia and hypertension 1

Psychiatric Adverse Reactions

Exacerbation of Pre-Existing Conditions:

• May exacerbate symptoms of behavior disturbance and thought disorder in patients with pre-existing psychotic disorders 1
• Can induce manic or mixed episodes in patients with bipolar disorder 1

New-Onset Psychiatric Symptoms:

• At recommended doses, may cause psychotic or manic symptoms (hallucinations, delusional thinking, mania) in patients without prior psychiatric history 1
• Pooled analysis shows psychotic/manic symptoms occur in approximately 0.1% of stimulant-treated patients versus 0% with placebo 1
• Screen patients for risk factors (comorbid/history of depressive symptoms, family history of suicide, bipolar disorder, or depression) before initiating treatment 1

Pregnancy and Fetal Risks

• Based on animal data, dextroamphetamine may cause fetal harm 2
• Human data are insufficient to determine risk 2
• Amphetamines cross the placental barrier 5
• Possible increased risk for gastroschisis (adjusted OR 3.0; 95% CI 1.2-7.4) and preeclampsia (adjusted RR 1.29; 95% CI 1.11-1.49) 5
• Continued stimulant use in second half of pregnancy may increase risk of preterm birth (adjusted RR 1.30; 95% CI 1.10-1.55) 5
• Monitor infants carefully for irritability, insomnia, and feeding difficulties if mother used amphetamines during pregnancy 5
• Amphetamines have been associated with possible increased risk for spontaneous abortion, though confounding by indication cannot be ruled out 5

Growth Suppression in Pediatric Patients

• CNS stimulants, including dextroamphetamine, are associated with weight loss and slowing of growth rate in pediatric patients 1
• Closely monitor growth (weight and height) in pediatric patients 1
• Pediatric patients not growing or gaining height/weight as expected may need treatment interruption 1

Common Adverse Effects

The most frequently reported adverse effects include: 2

• Sweatiness
• Edginess
• Weight changes (both gain and loss of appetite)
• Irritability

Overdose Presentation and Toxicity

Clinical Syndrome: The primary toxicity mechanism involves excessive extracellular dopamine, norepinephrine, and serotonin 6

Neurological Effects: 6

• Mydriasis
• Tremor, hyperreflexia
• Agitation, combative behavior
• Confusion, hallucinations, delirium
• Anxiety, paranoia
• Movement disorders
• Seizures

Cardiovascular Effects: 6, 7

• Tachycardia, tachypnea
• Hypertension
• Cardiac tachyarrhythmias

Other Complications: 6, 7, 8

• Hyperthermia (severe hyperpyrexia)
• Rhabdomyolysis
• Disseminated intravascular coagulation (DIC)
• Gastrointestinal bleeding
• Hepatic necrosis
• Renal failure
• Hyponatremia

Withdrawal Due to Adverse Effects

• Patients taking amphetamines are 2.69 times more likely to withdraw from treatment due to adverse effects compared to placebo (95% CI 2.13-3.40), representing an absolute risk increase of 4.3% 4

Chronic Use Complications

Long-term amphetamine abuse poses additional risks: 8

• Vasculitis
• Neuropsychiatric abnormalities
• Cardiomyopathy
• Potential long-lasting damage to dopaminergic and serotonergic neurons 8

Clinical Management Considerations

Before Prescribing: 1

• Assess each patient's risk for abuse, misuse, and addiction
• Screen for cardiovascular disease and psychiatric risk factors
• Educate patients and families about risks
• Advise on proper storage (preferably locked) and disposal

During Treatment: 1

• Reassess abuse/addiction risk throughout treatment
• Frequently monitor for signs/symptoms of abuse, misuse, and addiction
• Monitor blood pressure, heart rate, and growth (in pediatric patients)

Special Populations:

• The balance of risks and harms is likely different for pregnant and breastfeeding women 2
• Consider non-pharmacological interventions for ADHD during pregnancy 5