ADHD update: New data on the risks of medication

Medications — chiefly the stimulants dextroamphetamine and methylphenidate — are the only proven treatment for attention deficit hyperactivity disorder (ADHD), with its symptoms of distractibility, impulsiveness, and hyperactivity. But the benefits of stimulants last only as long as patients continue to take them, and worries about the risks of long-term use are again in the news.

Blood pressure and heart problems. Stimulants raise blood pressure and heart rate. New data are fueling a debate about how dangerous this is for people who take the drugs for extended periods. In 2005 Health Canada, the Canadian equivalent of the FDA, removed Adderall XR (an extended-release form of dextroamphetamine) from the market, citing a suspicious pattern of 20 sudden deaths and 12 strokes in children and adults taking the drug. The ban was lifted when many of these patients proved to have structural heart defects.

This spring an FDA panel reported on a study of physicians' reports on ADHD medications recorded in its Adverse Events Reporting System database. More than 300 people taking the medications died suddenly. Only 25 of these deaths appeared to be drug-related, and autopsies indicated pre-existing heart abnormalities in some of these cases. There were also 26 incidents of apparently drug-related symptoms such as chest pain, heart attacks, strokes, and arrhythmias. In a close vote, the panel members recommended the strongest possible action short of banning the drugs, a so-called black box warning of cardiovascular risk on prescription labels. They also unanimously recommended improved information sheets for physicians, patients, and families.

The FDA records were not easy to interpret. On the one hand, it's estimated that fewer than 10% of adverse drug effects are actually reported. On the other hand, the rate of sudden cardiac death in the survey was much lower than the average among children of the same age in the general population. After further analysis, a second FDA panel canceled the black box warning but agreed to strengthen present warnings about prescribing these medications to anyone with high blood pressure or heart defects.

Meanwhile, the Medicines and Healthcare Products Regulatory Agency, the British equivalent of the FDA, noted seizures and heart rate irregularities in a few people taking atomoxetine (Strattera), a new ADHD drug that is not a stimulant. The overwhelming majority of them had a prior history of seizures (which the drug did seem to exacerbate). Heart rate irregularities were less common and often associated with the use of antidepressants that interfered with the breakdown of atomoxetine. The British agency required updating of the drug's label.

The bottom line is that ADHD drugs are not likely to cause cardiovascular problems in anyone who does not already have underlying cardiac risk. But more such people are now using the drugs, because of the explosive growth in adult prescriptions. One estimate is that 1.5 million adults, 10% of them over age 50, now take stimulants for ADHD. Careful screening and monitoring make sense.

Growth suppression. Many children start taking ADHD medications young and stay on the drugs for years, so the effect on growth is a persisting concern. Three studies offer conflicting evidence. In the first study, 178 children ages 6–13 taking Concerta (a sustained-release form of methylphenidate) were followed for nearly two years. Their height and weight were average at the start; at the end, they were slightly shorter and lighter than average, but the difference could have been due to chance.

In a second study, 79 children ages 6–12 at the outset, also taking Concerta, were followed for up to five years. The results varied by age, sex, and dose, with overall small but statistically significant differences from the average in weight (about 3 pounds for a nine-year-old boy) and height (a little under an inch for a 13-year-old boy).

In a third, larger study with a broader focus, children ages 7–9 were followed for two years. At the end, those who had continuously taken ADHD medication during that time were on average half an inch shorter and 8 pounds lighter than those not taking the medication. To clarify the practical significance of this effect, researchers will have to do studies taking into account the adolescent growth spurt.

Abuse and diversion. Investigators at the Centers for Disease Control and Prevention examined the records of 64 hospital emergency departments and found 188 visits involving ADHD medications from August 2003 to December 2005. The overwhelming majority of the patients were children, and in 60% of cases the cause was intentional ingestion or an overdose, usually of a medication prescribed for someone else. About 15% of the patients had cardiovascular symptoms such as chest pain and high blood pressure; other symptoms included stomach pain, muscle weakness, and rashes.

The stimulants used to treat ADHD have some potential for abuse, because crushing pills and snorting (snuffing) them can produce a cocaine-like high. Several studies indicate that nearly 10% of students in grades 7–12 have used nonprescribed stimulants; that as many as a third of young ADHD patients have been asked to sell or give away their medications; and that 7%–15% have done so. A 10-year study suggested that 11% of adolescent and adult ADHD patients had sold the drugs at some time; 22% had taken more than prescribed; and 10% had used the drugs to get high. Nearly a third had used alcohol or other drugs while taking the ADHD medication, but only 5% had experienced bad side effects as a result.

More than 80% of the abusers already had a diagnosis of conduct disorder or substance abuse, so they were at high risk for selling or using illicit drugs of any kind. The overwhelming majority of abusers were taking immediate-release preparations. These are increasingly being supplanted by extended-release formulas (and a skin patch), which are absorbed so gradually that they don't cause a euphoric sensation and are therefore much less susceptible to misuse.

So, over all, new findings do not seriously challenge the consensus that most people who are properly diagnosed with ADHD will decide that the benefits of stimulant medications outweigh the risks.

Resources

Children And Adults with Attention Deficit/Hyperactivity Disorder800-233-4050 (toll free)www.chadd.org

This support and educational organization of parents of children with ADHD sponsors lectures, maintains support groups, publishes information, and refers patients for treatment.

National Institute of Mental Health www.nimh.nih.gov/healthinformation/adhdmenu.cfm

Provides information on symptoms, publications, research, treatment, clinical trials, and how to get services.

References

Charach A, et al. "Stimulant Treatment Over 5 Years: Effects on Growth," Journal of the American Academy of Child and Adolescent Psychiatry (April 2006), Vol. 45, No. 4, pp. 415–21.

MTA Cooperative Group. "National Institute of Mental Health Multimodal Treatment Study of ADHD Follow-up: 24-Month Outcomes of Treatment Strategies for Attention-Deficit/Hyperactivity Disorder," Pediatrics (April 2004), Vol. 113, No. 4, pp. 754–61.

MTA Cooperative Group. "National Institute of Mental Health Multimodal Treatment Study of ADHD Follow-up: Changes in Effectiveness and Growth After the End of Treatment," Pediatrics (April 2004), Vol. 113, No. 4, pp. 762–69.

Nissen SE. "ADHD Drugs and Cardiovascular Risk," New England Journal of Medicine (April 6, 2006), Vol. 354, No. 14, pp. 1445–48.

Spencer TJ, et al. "Does Prolonged Therapy with a Long-Acting Stimulant Suppress Growth in Children with ADHD?" Journal of the American Academy of Child and Adolescent Psychiatry (May 2006), Vol. 45, No. 5, pp. 527–37.

Wilens TE, et al. "Characteristics of Adolescents and Young Adults with ADHD Who Divert or Misuse Their Prescribed Medications," Journal of the American Academy of Child and Adolescent Psychiatry (April 2006), Vol. 45, No. 4, pp. 408–14.