What are the effects of long-term use of Adderall (amphetamine and dextroamphetamine)?

Long-Term Effects of Adderall Use

Long-term Adderall (amphetamine and dextroamphetamine) use is associated with increased risk of cardiovascular diseases, particularly hypertension and arterial disease, with risk increasing with duration of use beyond one year. 1

Cardiovascular Effects

• Prolonged Adderall use can lead to cardiovascular complications including palpitations, tachycardia, and elevated blood pressure 2
• Isolated reports of cardiomyopathy have been associated with chronic amphetamine use 2, 3
• A recent large case-control study found that longer cumulative duration of ADHD medication use was associated with an increased risk of cardiovascular disease compared to non-use 1:
  • 1-2 years use: 9% increased risk (AOR, 1.09)
  • 2-3 years use: 15% increased risk (AOR, 1.15)
  • 3-5 years use: 27% increased risk (AOR, 1.27)

  • 5 years use: 23% increased risk (AOR, 1.23) 1

• Hypertension risk is particularly elevated with long-term use (>5 years: AOR, 1.80) 1

Neurological and Psychiatric Effects

• Common central nervous system effects include:
  • Insomnia and sleep disturbances 2, 4
  • Restlessness and irritability 2, 4
  • Headaches 2, 4
  • Rare psychotic episodes even at recommended doses 2
  • Exacerbation of motor and phonic tics and Tourette's syndrome 2
• Long-term use may lead to tolerance, requiring higher doses to achieve the same therapeutic effect 2

Dependence and Withdrawal

• Amphetamines have been extensively abused with potential for extreme psychological dependence 2
• Abrupt cessation after prolonged high-dose use can result in:
  • Extreme fatigue
  • Mental depression
  • Changes in sleep EEG patterns 2
• Chronic intoxication manifestations include:
  • Severe dermatoses
  • Marked insomnia
  • Irritability
  • Hyperactivity
  • Personality changes 2
• The most severe manifestation of chronic intoxication is psychosis, which can be clinically indistinguishable from schizophrenia (though rare with oral amphetamines) 2

Gastrointestinal and Metabolic Effects

• Common gastrointestinal effects include:
  • Dry mouth
  • Unpleasant taste
  • Diarrhea or constipation 2
• Decreased appetite and weight loss are common side effects 4, 2
• Growth suppression may occur in children with prolonged use 4

Endocrine Effects

• Long-term use may cause:
  • Impotence
  • Changes in libido 2
  • Hormonal dysregulation that may contribute to growth suppression 4

Effectiveness with Long-Term Use

• While short-term efficacy of psychostimulants is well-established, longer-term effects have been less well investigated 4
• Some observational data suggest that children with ADHD who continued psychostimulants for more than 10 years showed no better symptom reduction than those who discontinued medication 4
• However, a 24-month study of extended-release mixed amphetamine salts in children with ADHD showed maintained significant behavioral improvements during long-term treatment 5

Clinical Monitoring Recommendations

• Regular cardiovascular monitoring is essential, including blood pressure and heart rate checks 4, 1
• Periodic assessment of continued need for medication, potentially including medication-free intervals 4
• Monitoring for growth in children on long-term therapy 4
• Assessment for signs of tolerance, dependence, or abuse 2

Caveats and Considerations

• Individual response to Adderall varies significantly; some patients may experience minimal side effects while others experience significant adverse reactions 4
• Benefits of treatment must be weighed against potential risks, especially for long-term use 1
• Patients with pre-existing cardiovascular conditions may be at higher risk for adverse effects 4
• The risk of cardiovascular effects appears to increase most significantly in the first 3 years of cumulative use 1