What are the absolute and relative contraindications for initiating stimulant therapy (amphetamine or methylphenidate) in a patient?

Contraindications and Relative Contraindications for Starting Stimulants

Stimulants must not be used in patients taking MAO inhibitors, those with active psychotic disorders, or those with recent stimulant abuse history unless in a controlled setting. 1, 2

Absolute Contraindications

The following conditions represent true contraindications where stimulants should not be initiated:

Medication Interactions

• Concomitant MAO inhibitor use or use within the preceding 14 days—this combination causes severe hypertension and risk of cerebrovascular accident 1, 2

Psychiatric Conditions

• Active psychotic disorders including schizophrenia, psychosis NOS, or manic episodes with psychosis—stimulants are psychotomimetic in these patients and will worsen symptoms 1

Substance Use

• Recent stimulant drug abuse or dependence—FDA black box warning applies unless patient is in a controlled treatment setting with close supervision 1
• Note: History of other substance abuse (alcohol, opiates, benzodiazepines, cigarettes) does not preclude stimulant use, though closer monitoring is required 1

Ophthalmologic Conditions

• Glaucoma—sympathomimetics including stimulants may increase intraocular pressure 1, 2
• For patients with open-angle glaucoma or abnormally increased intraocular pressure, prescribe only if benefits outweigh risks and monitor closely 2

Cardiovascular Conditions

• Symptomatic cardiovascular disease, including known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, or coronary artery disease 1, 2
• Hyperthyroidism 1
• Hypertension (uncontrolled) 1

Other Medical Conditions

• Known hypersensitivity to methylphenidate or stimulant components 2
• Preexisting liver disease or abnormal liver function tests (specifically for pemoline, though this agent is rarely used due to hepatotoxicity) 1

Relative Contraindications (Conditions NOT Supported as Contraindications by Recent Evidence)

The American Academy of Child and Adolescent Psychiatry guidelines explicitly state that several FDA package insert contraindications are not supported by controlled trial data: 1

Motor Tics and Tourette's Syndrome

• Controlled studies show methylphenidate does not worsen motor tics in Tourette's syndrome or in children with ADHD without Tourette's 1
• Amphetamine may worsen tics more than methylphenidate in some patients 1
• Monitor for dose-dependent tic worsening, but tics alone are not a contraindication 1

Depression

• Not a contraindication—stimulants can produce dysphoria in vulnerable patients, but many ADHD patients with secondary depression improve when ADHD is treated 1
• Use caution in patients with unstable mood disorders 1

Anxiety Disorders

• Not a contraindication—children with comorbid anxiety disorder actually improve on methylphenidate 1

Seizure Disorders

• Not a contraindication if seizures are controlled—stabilize on anticonvulsants first, then initiate stimulants 1
• Studies show epileptic patients on anticonvulsants do not show increased seizure frequency when methylphenidate is added 1

Age Considerations

• Children under age 6: Package insert warns against methylphenidate use, but 7-8 published double-blind studies in 241+ preschoolers show good efficacy with somewhat higher adverse effect rates 1
• Paradoxically, amphetamine/dextroamphetamine are FDA-approved down to age 3 despite no published controlled data in preschoolers 1

Clinical Approach to Borderline Cases

Cardiovascular Risk Assessment

• Before initiating stimulants: Screen for structural cardiac abnormalities, cardiomyopathy, arrhythmias, and coronary artery disease 2
• Monitor blood pressure and pulse throughout treatment 2
• In rare cases where quality of life severely deteriorates off medication despite cardiovascular risk, shared decision-making with documented informed consent may be appropriate 3

Substance Use History

• Non-stimulant substance abuse history (alcohol, opiates, benzodiazepines) requires closer monitoring but is not a contraindication 1
• Remote stimulant abuse history may not represent absolute contraindication with appropriate supervision 1
• Ensure household members do not have active stimulant abuse to prevent diversion 1

Growth Concerns (Low BMI)

• Low BMI is not a contraindication if ADHD causes moderate-to-severe impairment in at least two settings 4
• Requires responsible adult to monitor medication administration and nutritional intake 4
• Monitor weight at each visit during titration and track growth charts regularly 4

Common Pitfalls to Avoid

• Do not rely solely on FDA package inserts—they list conditions (tics, anxiety, family history of Tourette's) that controlled trials have not validated as contraindications 1
• Do not assume all cardiovascular disease is equal—symptomatic disease is a contraindication, but well-controlled hypertension with monitoring may be manageable 1, 2
• Do not confuse therapeutic dosing with abuse patterns—neurotoxicity occurs at doses 50-80 times therapeutic levels via parenteral routes, not with standard oral dosing 5
• Do not overlook household diversion risk—if family members have stimulant abuse history, implement safeguards for medication storage 1