Pharmacologic Treatment of ADHD

Posted by Carla Rothaus

What side effects are associated with stimulant use for ADHD?

Attention deficit–hyperactivity disorder (ADHD) is characterized by hyperactivity and impulsivity, by inattention, or by a combination of hyperactivity, impulsivity, and inattention that is inconsistent with developmental level and impairs daily function. Medications approved by the Food and Drug Administration comprise stimulants (amphetamines and methylphenidate) and nonstimulants (atomoxetine and extended-release clonidine and guanfacine). Read the NEJM Review Article here.

Clinical Pearls

Q: What is first-line treatment for ADHD?

A: Stimulants have generally been recommended as first-line pharmacologic treatment. A meta-analysis of double-blind, randomized, controlled trials with an average duration of 7 weeks showed that medications approved for ADHD were superior to placebo in decreasing the severity of inattention, hyperactivity, and impulsivity as rated by clinicians, with the largest effect sizes found for amphetamines, followed by methylphenidate. Determining the long-term effects of ADHD medications has been challenging because of the difficulty in overcoming bias and confounding in studies comparing treated and untreated patients.

Q: Is it known how ADHD medications affect the brain?

A: Our current knowledge of the molecular targets of ADHD medications in the brain does not directly inform the choice of medication in clinical practice, but these mechanisms are useful in understanding the effects of the medications. Across randomized trials, the most consistent effect of a single dose of stimulants is enhancement during neuropsychological tasks of the activity of the right inferior frontal cortex and insula, which together are involved in attention control and inhibition. Methylphenidate also temporarily normalizes the pattern of activation of other brain networks, such as the default network, which is usually deactivated in everyone during tasks requiring attention but is less deactivated in people with ADHD who have not received treatment.

Morning Report Questions

Q: What are some of the reasons that patients discontinue medications for ADHD?

A: Across the 12-month follow-up periods of various studies in a systematic review, the average duration of treatment with stimulants was 136 days in children and 230 days in adults. The highest rates of discontinuation of medication were reported in patients who were 15 to 21 years of age, and reasons for discontinuation included side effects, perceived lack of effectiveness, dislike of taking medications, a decision that treatment was not needed, stigma, and issues with the transition from child to adult services. 

Q: What side effects are associated with stimulant use for ADHD?

A: Short-term trials have shown significant increases in heart rate or blood pressure in persons with ADHD treated with stimulants or atomoxetine, as compared with placebo; in a meta-analysis of randomized controlled trials (RCTs) of stimulants in adults, the average increase in heart rate was 5.7 beats per minute, and the average increase in systolic blood pressure was 2.0 mm Hg. Across RCTs, electrocardiographic changes considered to be abnormal have not been observed or have occurred in less than 2% of participants; however, patients with preexisting cardiovascular conditions were likely to have been excluded from these trials. Stimulant use in children with ADHD has reduced growth in height by as much as 1 cm per year during the first 3 years of treatment. Pooled data from studies in 6-to-7-year-old children showed that after treatment with atomoxetine for 2 years, height was approximately 2.7 cm less than expected according to baseline height percentiles.

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