What are the potential side effects of methylphenidate in children, adolescents, and young adults with Attention Deficit Hyperactivity Disorder (ADHD) or narcolepsy?

Methylphenidate Side Effects in Children, Adolescents, and Young Adults

Most Common Non-Serious Adverse Effects

The most frequently reported side effects of methylphenidate include decreased appetite (31.1%), insomnia and sleep problems (17.9%), headache (14.4%), abdominal pain (10.7%), dry mouth, sweating, and stomach discomfort. 1, 2

Gastrointestinal and Appetite Effects

• Decreased appetite affects approximately one-third of patients (31.1%, 95% CI 26.5% to 36.2%) and represents the single most common non-serious adverse effect 2
• Abdominal pain occurs in 10.7% (95% CI 8.60% to 13.3%) of patients on methylphenidate 2
• Dry mouth and stomach discomfort are commonly reported with long-term treatment 1

Sleep Disturbances

• Difficulty falling asleep affects 17.9% (95% CI 14.7% to 21.6%) of children and adolescents taking methylphenidate 2
• Methylphenidate increases the risk of insomnia and sleep problems by 2.58-fold compared to no treatment (RR 2.58,95% CI 1.24 to 5.34) 2
• Insomnia can be managed by administering doses earlier in the day and lowering the final dose 3

Neurological Effects

• Headache occurs in 14.4% (95% CI 11.3% to 18.3%) of patients 2
• Sweating and hyperhidrosis are frequently reported 1, 4

Cardiovascular Effects

• Tachycardia and palpitations are common adverse reactions listed in FDA labeling 4
• Blood pressure and heart rate must be measured before initiating treatment and at each follow-up visit 5

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Serious Adverse Events and Black Box Warnings

Abuse, Misuse, and Addiction Risk

Methylphenidate is an FDA Schedule II federally controlled substance with a black box warning for high potential for abuse and misuse, which can lead to substance use disorder, including addiction. 1, 4

• Before prescribing, assess each patient's risk for abuse, misuse, and addiction, and educate patients and families about proper storage and disposal 4
• The medication should be given cautiously to patients with a history of drug dependence or alcoholism 1
• Approximately 4% of older teens and emerging adults in the US annually misuse methylphenidate 6
• Throughout treatment, frequently monitor for signs and symptoms of abuse, misuse, and addiction 4

Cardiovascular Risks

Methylphenidate is contraindicated in patients with uncontrolled hypertension, underlying coronary artery disease, and tachyarrhythmias due to increased risk of cardiovascular adverse effects. 5

• Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease 4
• Methylphenidate increases the risk of arrhythmia by 1.61-fold (RR 1.61,95% CI 1.48 to 1.74) compared to no intervention 2
• The American College of Cardiology recommends measuring blood pressure and heart rate before initiating treatment and at each follow-up visit 5

Psychiatric Adverse Events

Methylphenidate increases the risk of any psychotic disorder by 1.36-fold (RR 1.36,95% CI 1.17 to 1.57) compared to no intervention. 2

• Prior to initiating methylphenidate, screen patients for risk factors for developing a manic episode 4
• If new psychotic or manic symptoms occur, consider discontinuing methylphenidate 4
• Some evidence suggests an elevated risk of psychosis and tics, though case reports describe remission on discontinuation 7
• Common neuropsychiatric effects include anxiety, irritability, and edginess 1, 4
• Memory impairment or "patchy memory" is not a typical therapeutic response—the drug should improve attention and working memory, not impair episodic memory formation 5

Growth Suppression in Pediatric Patients

The American Academy of Pediatrics recommends regular monitoring of height and weight in pediatric patients taking methylphenidate due to potential for growth suppression. 5

• Closely monitor height and weight in pediatric patients throughout treatment 4
• Pediatric patients not growing or gaining height or weight as expected may need to have their treatment interrupted 4

Other Serious Adverse Events

• Overall, 1.20% (95% CI 0.70% to 2.00%) of participants on methylphenidate experience any serious adverse event 2
• Priapism: If abnormally sustained or frequent and painful erections occur, patients should seek immediate medical attention 4
• Peripheral vasculopathy, including Raynaud's phenomenon: Careful observation for digital changes is necessary during treatment 4
• Acute angle closure glaucoma: Patients at risk (e.g., those with significant hyperopia) should be evaluated by an ophthalmologist 4
• Increased intraocular pressure: Prescribe to patients with open-angle glaucoma only if benefit outweighs risk 4

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Special Population Considerations

Pregnancy and Breastfeeding

• Based on animal data, methylphenidate may cause fetal harm, though human data are insufficient to determine risk 1
• The balance of risks and harms is likely different for pregnant and breastfeeding women 1

Patients with Intellectual Disability

Children with intellectual disability may be more sensitive to side effects of methylphenidate, and conservative dosing is generally recommended. 1

• The adverse effects experienced by children with intellectual disability in randomized trials were similar to those in children with typical development, primarily appetite suppression and sleep problems 1
• Methylphenidate can be considered in children with ADHD and intellectual disability regardless of severity 1

Patients with Tics or Tourette's Syndrome

• Before initiating methylphenidate, assess family history and clinically evaluate patients for tics or Tourette's syndrome 4
• Regularly monitor patients for the emergence or worsening of tics or Tourette's syndrome 4
• Discontinue treatment if clinically appropriate 4
• Evidence suggests caution in specific groups including those with tics 7

Preschool-Aged Children

• Evidence suggests caution in preschool children, as they may experience more frequent or severe adverse effects 7
• Methylphenidate is the recommended first-line pharmacologic treatment for preschool children with moderate-to-severe ADHD, though use remains off-label 1

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Withdrawal Rates Due to Adverse Events

• Withdrawal from methylphenidate due to serious adverse events occurs in 1.20% (95% CI 0.60% to 2.30%) of patients 2
• Withdrawal due to non-serious adverse events occurs in 6.20% (95% CI 4.80% to 7.90%) of patients 2
• An additional 16.2% (95% CI 13.0% to 19.9%) are withdrawn for unknown reasons 2
• Adverse events of unknown severity lead to withdrawal in 7.30% (95% CI 5.30% to 10.0%) of participants 2

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Critical Clinical Pitfalls to Avoid

• Do not assume all late-day irritability is rebound—peak effects occurring 1-3 hours after dosing can also cause irritability if doses are too high 3
• Do not ignore timing patterns—document when symptoms occur relative to dosing to distinguish peak effects from rebound effects 3
• Do not use older sustained-release formulations expecting full-day coverage, as they only provide 4-6 hours of action 3
• Avoid scheduling any methylphenidate dose after 2:00 PM to minimize sleep disruption 3
• Methylphenidate is contraindicated with MAOIs and should not be used within 14 days of MAOI discontinuation 4

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Quality of Evidence Note

The overall quality of evidence regarding methylphenidate adverse events is very low, with most non-comparative studies at critical risk of bias. 2 The actual risk of adverse events may be higher than reported, and large-scale, high-quality randomized controlled trials are needed to accurately estimate risks 2. Despite these limitations, the consistent pattern of adverse effects across multiple studies and guideline recommendations provides a reasonable basis for clinical decision-making and patient counseling.