What are the common side effects of stimulant medication, such as Ritalin (methylphenidate) and Adderall (amphetamine and dextroamphetamine), in patients with attention deficit hyperactivity disorder (ADHD) or narcolepsy?

Common Side Effects of Stimulant Medication

The most common side effects of stimulant medications (methylphenidate and amphetamines) are appetite suppression, insomnia, abdominal pain, headaches, and weight loss, with these effects occurring significantly more often than placebo but typically being mild, short-lived, and responsive to dose or timing adjustments. 1

Most Frequent Side Effects

According to the American Academy of Child and Adolescent Psychiatry, placebo-controlled studies identify seven side effects that occur significantly more often with stimulants than placebo 1:

• Delayed sleep onset/insomnia - among the most commonly reported effects 1, 2
• Reduced appetite/anorexia - identified as a primary adverse effect common to all stimulants 1, 2
• Weight loss - can occur and requires monitoring 1
• Tics - may emerge or worsen 1
• Stomach-ache/abdominal pain - frequently reported 1
• Headache - common but typically transient 1, 2
• Jitteriness - reported with both stimulant types 1, 2

Cardiovascular Effects

Stimulants cause mild increases in heart rate and blood pressure that are clinically insignificant for most patients but require monitoring. 1

• Average increases: 1-2 beats per minute for heart rate and 1-4 mm Hg for systolic and diastolic blood pressure 1
• A subset of individuals (5%-15%) may experience more substantial increases requiring closer monitoring 1
• Research confirms statistically significant but small pre-post increases in systolic blood pressure with all stimulants (methylphenidate SMD 0.25, amphetamines SMD 0.09) 3
• Amphetamines show additional small increases in diastolic blood pressure (SMD 0.16) and heart rate (SMD 0.37) 3
• Adult studies demonstrate similar patterns with amphetamines causing +5.4 mm Hg systolic increases and +7.3 bpm heart rate increases 4

Growth Effects

Long-term stimulant use can decrease growth velocity by 1-2 cm from predicted adult height, particularly with higher and more consistently administered doses. 1

• The MTA study identified more persistent effects on growth compared to earlier studies 1
• Effects diminished by the third year of treatment, but no compensatory rebound growth was observed 1
• Weight should be measured at each visit as an objective measure of appetite loss 1

Differences Between Stimulant Types

Dexamphetamine causes more severe emotional and sleep-related side effects compared to methylphenidate at equivalent doses. 5

A double-blind crossover study of 125 children found six side effects significantly more severe with dexamphetamine than methylphenidate 5:

• Insomnia (more severe with dexamphetamine) 5
• Irritability 5
• Proneness to crying 5
• Anxiousness 5
• Sadness/unhappiness 5
• Nightmares 5

Both medications caused appetite suppression, but only dexamphetamine caused insomnia more severe than baseline 5. Notably, only 1.6% of subjects discontinued each stimulant due to severe adverse effects 5.

Rare but Serious Side Effects

Serious side effects are rare and short-lived if medication is reduced or discontinued. 1

• Severe movement disorders, obsessive-compulsive ruminations, or psychotic symptoms are very rare and disappear when medication is stopped 1
• Hallucinations and other psychotic symptoms are uncommon but significant adverse effects 1
• Sudden cardiac death is extremely rare and stimulants have not been shown to increase risk beyond baseline rates in children without pre-existing cardiac abnormalities 1
• New-onset hypertension (BP ≥140/90) occurred in 10% of medication-treated adults versus 8% on placebo 4

Management Strategies

Most side effects can be alleviated through dose reduction or timing adjustments without discontinuing medication. 1, 2

For Sleep Disturbances:

• Administer stimulants early in the day 2
• Implement consistent bedtime routines 2
• Consider dose reduction or timing changes 1, 2

For Appetite Loss:

• Provide high-calorie evening snacks 2
• Administer medication with meals 2
• Monitor weight at each visit 1

For Cardiovascular Effects:

• Monitor blood pressure and heart rate at baseline and regularly during treatment 1, 4
• Obtain cardiac history including family history of sudden death, cardiovascular symptoms, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, and long QT syndrome before initiating treatment 1
• If risk factors present, obtain additional cardiac evaluation before starting stimulants 1

Monitoring Schedule

Side effects should be systematically assessed by asking specific questions about known side effects at each visit. 1

• During initial titration (2-4 weeks), maintain weekly contact by telephone 1
• After stabilization, schedule appointments at least monthly 1
• More frequent appointments are warranted if side effects persist 1
• Weigh patient at each visit for objective appetite monitoring 1

Important Clinical Distinctions

Many symptoms commonly attributed to stimulant medication are actually pre-existing characteristics of ADHD that improve with treatment. 5

• Staring, daydreaming, irritability, anxiety, and nail-biting may decrease with increasing dose, representing preexisting symptoms rather than side effects 1
• Parents reported a greater mean number (8.19) and severity (4.08) of "side effects" before commencing stimulant trials than during methylphenidate treatment (number 7.19, severity 3.24) 5

Discontinuation Rates

Only 2% of patients discontinued medication treatment due to cardiovascular effects, and most cardiovascular effects resolved spontaneously or with dose adjustments. 3

• Amphetamines were associated with higher attrition due to adverse events overall (RR 2.69) 6
• In the majority of patients, cardiovascular effects were not considered clinically relevant 3
• Overall discontinuation due to severe adverse effects was only 1.6% for each stimulant type in pediatric populations 5