ADHD: Risk Reduction

Risks Related to ADHD Medications

Medication treatment risks usually relate to one or more of the following categories:

• Inappropriate prescribing (incorrect diagnosis, contraindication)
• Adverse reactions (Adverse Effects of Selected Medication Used in the Treatment of ADHD in Adults)
• Potential for abuse, misuse or diversion of stimulant medications
• Insufficient monitoring
• Insufficient secondary and tertiary prevention (reliance on medications only, no support/scaffolding, no accommodations, no skill building etc.)

Stimulant and related medications are generally well tolerated. Stimulant side effects are usually mild and respond to waiting, adjustment of dose, timing, or change in medication.

Medication Warnings

Stimulant products have a high potential for abuse. Stimulant products carry cardiovascular side effects, including tachycardia, palpitations, and blood pressure elevations. As a result, blood pressure should be monitored in those even with mild hypertension.  Uncontrolled hypertension should be controlled prior to starting stimulant therapy. Warnings exist with stimulants regarding the potential risk of serious cardiovascular events, of sudden death with use in those with pre-existing structural cardiac abnormalities or other serious heart problems. 

Additional adverse reactions with stimulants include insomnia, decreased appetite with possible weight loss, overstimulation, restlessness, dry mouth, unpleasant taste, diarrhea, and constipation.

The amphetamine group is also associated with dizziness, euphoria, dyskinesia, tremor, exacerbations of motor and phonic tics, and Tourette’s syndrome. Clinical evaluation and review of family history for tics and Tourette’s syndrome should precede use of stimulant medication.  

• 2013: FDA  Warning that methylphenidate and atomoxetine, may in rare instances cause prolonged and sometimes painful erections known as priapism. Priapism appears to be more common in patients taking atomoxetine than in those taking methylphenidate products.
• 2014: FDA Warning about Bruxism (as a form of akathisia) seen with Adderall and Adderall XR
• 2015: FDA Warning about Rhabdomyolysis seen with all stimulants and atomoxetine.

All stimulant medications are Schedule II prescriptions that are subject to Drug Enforcement Agency (DEA) regulations. All stimulant medications are Pregnancy Category C except for guanfacine (Category B).

Treated vs Untreated ADHD

The evidence on the long-term disease outcomes of treated versus untreated ADHD is somewhat inconsistent. Some studies in both children and adults concluded that ADHD individuals left untreated had poorer long-term outcomes compared to treated individuals in several major categories including academics, antisocial behavior, driving, non-medical drug use/addictive behavior, obesity, occupation, services use, self-esteem, and social function outcomes. However, treatment in these studies did not result in normalization. Studies also found that ADHD medications reduce ADHD symptoms and impairments, but that there is limited and inconsistent evidence for long-term medication effects on improved social functioning, academic achievement, employment status, and psychiatric comorbidity. Although some studies show an association between ADHD and suicidality, depression, and substance use disorder, some emerging evidence suggests that these co-occurrence could be due to shared familial risk factors rather than to harmful effects of ADHD medications.

Risk Reduction Strategies

Stimulant products and atomoxetine should generally not be used in patients with serious heart problems, or for whom an increase in blood pressure or heart rate would be problematic. Periodically monitor patients for changes in heart rate and blood pressure

Stimulant products are contraindicated for persons with the following co-existing conditions:

• Comorbid Tourette’s disorder
• Thyrotoxicosis
• Arrhythmias
• Uncontrolled moderate to severe hypertension
• Active angina
• Pheochromocytoma
• Glaucoma 
• Alcohol use disorder
• Anorexia nervosa

Clinical Bottom Line for Stimulants and Abuse Potential

Universal-precautions should be applied to all adult ADHD patients for whom stimulants are being considered. Universal-precautions include:

• careful diagnosis and consideration of indications, contraindications and comorbidities
• baseline risk stratification (Interventions for Minimizing Drug Misuse Based on Patient Risk)
• informed consent processes
• avoid short acting stimulants where possible
• treatment agreements
• periodic reassessments of treatment response
• meticulous documentation

Assume all patients are at risk of misuse, abuse, diversion, or having their medications stolen. Physicians should prescribe agents with less potential for abuse and monitor patients more intensely. Short-acting stimulant medications are the most likely to be abused and longer-acting stimulant medications less likely to be abused.