Pediatric Psychopharmacology for Primary Care Digital Tool

Name
Amphetamine

Brand Name
Adderall

Class
Stimulant

Indications
ADHD

Formulation
Immediate-release (DL-tablet)

Duration of Effect
4–8 hours

Initial Dose
5 mg in the early morning and 5 mg about 4 hours later (around lunch time)

Maximum daily dose
40 mg

Available unit dose forms
5, 7.5, 10, 12.5, 15, 20, or 30 mg

Dosage Adjustments

• Increase weekly by an amount equivalent to the starting dose.
• If feasible, collect parent and teacher ratings between dose adjustments.
• If there is a clear and positive response to the medication and no or minimal adverse effects, dose adjustments may be more frequent, as long as more frequent communication occurs with the caregiver(s) and school personnel.​

Monitoring Therapeutic Response During Dose Adjustments
During dose adjustment, a weekly phone check-in or appointment is preferred. Caregiver and teacher NICHQ Vanderbilt Assessment Scale reports can facilitate the tracking of changes in severity of symptoms.

Vital Signs, Physical Examination, and Laboratory Monitoring

• For all amphetamine preparations, monitoring blood pressure, heart rate, height, and weight is recommended.
• Patients taking stimulants should be observed for, and caregivers should be questioned about, tics.
• No specific laboratory monitoring is recommended.​

Optimizing Dose

• A general recommendation for optimizing dose—if confident that the child has adhered to the previously prescribed dose—is to continue to increase the dose until the benefit-to-risk ratio is optimized or the maximum recommended dose is achieved.
• Treatment response, assessed systematically using information from caregiver and teacher reports (eg, NICHQ Vanderbilt Assessment Scale ratings), should be considered alongside reported and observed adverse effects during dose escalation. Satisfaction of the caregiver, teacher, and child regarding the child's response can also be useful.
• Ideally, a consensus will emerge about the preferred dose that maximizes the benefit-to-risk ratio.​

Maintenance

• Once an optimal dose is determined, maintenance treatment begins.
• Frequency of monitoring can be reduced, usually to follow-ups every 1 to 3 months, depending on the patient's needs.
• Consideration of dose adjustments is recommended annually or more often if the patient's clinical status changes significantly.​

Medication Holidays

• Particularly for patients with amphetamine-induced growth suppression, medication "holidays" may be beneficial.
• Discontinuation of medication during a summer school recess may be sufficient to allow a growth "rebound."​

What if an Amphetamine Preparation Is Ineffective or Not Tolerated?

• If adverse effects limit dose escalation or if the initial medication is not considered sufficiently beneficial, discontinuation is recommended.
• If continued medication treatment is clinically indicated, consideration of another ADHD medication may be warranted.
• Available data suggest that a methylphenidate or an amphetamine preparation is effective in almost all children, so switching from one to the other is generally indicated if the first is ineffective.​

Discontinuing Amphetamine and Possible Withdrawal Adverse Effects

• For most patients, particularly those receiving extended-release (ER) preparations at recommended dosages, amphetamine can be discontinued abruptly.
• To minimize withdrawal adverse effects, particularly for patients receiving high doses, staggered discontinuation of amphetamine over a few days to weeks could be considered if withdrawal effects are anticipated or occur.
• Potential withdrawal adverse effects include anxiety, irritability, insomnia, and increased blood pressure.​

Switching From an Amphetamine to a Methylphenidate Preparation
Switching from an amphetamine preparation to a comparable methylphenidate one can be done abruptly, as long as the total daily dose is clinically comparable (ie, the amphetamine total daily dose is about one-half to three-quarters of the methylphenidate total daily dose).

When to Consult or Refer

• In general, consultation with, or referral to, a child and adolescent psychiatrist or other prescribing specialist may be considered when there is lack of clarity about diagnosis or after several medications have been tried and discontinued because of lack of effect or tolerability.
• A more extensive discussion regarding what to do when interventions fail is presented in Part 4 of the book.​

Contraindications

• Known hypersensitivity or idiosyncrasy to amphetamine products
• Symptomatic cardiovascular disease
• Moderate-to-severe hypertension
• Hyperthyroidism
• Glaucoma
• Agitated states
• History of drug abuse
• Currently using, or within 2 weeks of using, an MAOI​

Boxed Warnings

• Concerns about abuse and dependence. The boxed warnings for amphetamines state that they have a high potential for abuse and that prolonged administration may lead to dependence. Fortunately, there are no reports of children who were treated with therapeutic doses of stimulants developing dependence. Available data suggest that children with ADHD who are treated with stimulants are not more likely than those who did not receive stimulants to develop substance abuse later in life. A related problem is diversion—that is, patients selling their prescription stimulants to be used as cognitive enhancers or drugs of abuse.

Warnings and precautions
Most warnings and precautions rarely occur in children and adolescents treated with stimulants. Those most relevant to youth taking amphetamine preparations include

• Serious cardiovascular reactions and sudden death have been reported, most often in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious heart problems, but additional research is needed. Assessment prior to prescribing any ADHD medication, including stimulants, should include a targeted personal and family cardiac history and physical examination, with emphasis on the presence of structural heart defects, syncope, sudden unexplained death, and arrhythmias, particularly long QT syndromes. The present standard of care suggests that the decision to obtain an ECG prior to prescribing stimulant medication is a matter of physician judgment, considered to be reasonable but not mandatory in the absence of other findings.
• Blood pressure and heart rate increases
• Psychiatric adverse reactions (primarily emergence of psychotic, manic, or aggressive symptoms [or a combination of those])
• Long-term suppression of growth
• Peripheral vasculopathy, including Raynaud phenomenon (rare in children and adolescents)
• Seizures​
• Exacerbation of tics​

Adverse reactions
Across the package inserts for various amphetamine preparations, there is variation in the adverse effects listed. Those reported most consistently are

• Abdominal pain
• Appetite suppression
• Insomnia
• Weight loss
• Nervousness​

Drug Interactions
Drug interactions include

• Monoamine oxidases (current or within 14 days) may potentiate the effects of amphetamine.
• Alkalinizing agents may increase blood levels of amphetamine.
• Acidifying agents may reduce blood levels of amphetamine.
• Effects of α-adrenergic blocking agents, antihistamines, antihypertensives, phenobarbital, phenytoin, Veratrum alkaloids, and ethosuximide may be reduced by amphetamine.
• Effects of tricyclic antidepressants, norepinephrine, and meperidine may be potentiated by amphetamine.​