FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in adults

This update is in follow-up to the FDA Communication about an Ongoing Safety Review of Stimulant Medications used in Children with Attention-Deficit/Hyperactivity Disorder (ADHD).

Safety Announcement
Additional Information for Patients
Additional Information for Healthcare Professionals
Data Summary

Safety Announcement

[12-12-2011] The U.S. Food and Drug Administration (FDA) is updating its communication on the ongoing cardiovascular safety review of medications used for treating Attention-Deficit/Hyperactivity Disorder (ADHD), many of which are known to increase heart rate and blood pressure. A large, recently-completed study that included one study that evaluated heart attacks and sudden deaths in a sample of adults, and a second study that assessed strokes in these adults, has not shown an increased risk of serious adverse cardiovascular events in adults treated with ADHD medications.

The medications studied include stimulants (amphetamine products and methylphenidate), atomoxetine, and pemoline (no longer marketed).

ADHD medications involved in this safety review

Stimulants

methylphenidate (Concerta, Daytrana, Metadate CD, Metadate ER, Methylin, Methylin ER, Ritalin, Ritalin-LA, Ritalin-SR)
dexmethylphenidate HCl (Focalin, Focalin XR)
dextroamphetamine sulfate (Dexedrine, Dexedrine Spansules, Dextroamphetamine ER, Dextrostat)
lisdexamfetamine dimesylate (Vyvanse)
amphetamine, mixed salts (Adderall, Adderall XR)
methamphetamine (Desoxyn)

Non-stimulants

pemoline (Cylert-no longer marketed)
atomoxetime (Strattera)

FDA recommendations for the use of medications to treat ADHD have not changed. Healthcare professionals should continue to take special note that:

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.
Patients treated with ADHD medications should be periodically monitored for changes in heart rate or blood pressure.

Patients should continue to use their medicine for the treatment of ADHD as prescribed by their healthcare professional.

In the two recently-completed epidemiologic studies, data were analyzed from over 440,000 adults aged 25-64 years, including over 150,000 adults treated with medications for ADHD. One study evaluated heart attacks and sudden cardiac deaths in this sample of adults, and the second study assessed strokes in these adults. Together, these studies were designed to evaluate the potential increased risk of heart attack (myocardial infarction, or MI), sudden cardiac death, or stroke that could be associated with the use of ADHD medications. The adult study is being published in the Journal of the American Medical Association on December 12, 2011.¹

On November 1, 2011, FDA communicated the results of a study in children and young adults treated with ADHD medications that also did not show an increased risk of serious cardiovascular events. This study was published in the New England Journal of Medicine on November 1, 2011.² The Drug Safety Communication may be found here.

FDA is releasing the following documents today:

Study Reports:

Final Study Report: ADHD Medications and Risk of Stroke in Young and Middle-Aged Adults (PDF - 836KB)

FDA Reviews:

Additional Information for Patients or Caregivers

Continue your ADHD treatment as prescribed by a healthcare professional.
Talk to your healthcare professional about any questions you may have about ADHD medications.
Immediately see a healthcare professional if you or the person you are caring for develops chest pain, shortness of breath or fainting while taking medication to treat ADHD,
Report any suspected side effects of ADHD medication use to your healthcare professional or to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of the page.

Additional Information for Healthcare Professionals

A large retrospective cohort study in adults (aged 25-64 years) did not show an increased risk of MI, stroke, or sudden cardiac death with use of ADHD medications.
Continue to prescribe drugs used for the treatment of ADHD according to the professional prescribing directions.
Report adverse events involving ADHD medications to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of the page.

Data Summary

Blood pressure and heart rate increases have been observed in patients treated with the sympathomimetics methylphenidate and amphetamine, and with atomoxetine. In view of these effects, together with spontaneous postmarketing reports of serious cardiovascular events with use of ADHD drugs, FDA, in partnership with AHRQ, sponsored three related observational studies of serious cardiovascular events with drugs for ADHD. One study assessed myocardial infarction (MI), stroke, and sudden cardiac death (SCD) with use of ADHD drugs by children and young adults aged 2-24 years; a second study assessed MI and SCD among non-elderly adult users (aged 25-64 years); and the third study evaluated stroke in non-elderly adult users (aged 25-64 years). The third study also included an analysis of a composite endpoint (SCD plus MI plus stroke) in adults.

Each study was a retrospective cohort study using health care claims databases from several sources: Kaiser Permanente, Tennessee Medicaid, Washington State Medicaid, Ingenix, and HMO Research Network. Drug exposures were identified from prescription claims data. Outcomes of stroke, MI, or SCD were identified from diagnoses in claims data, and from searches of vital statistics and death certificate data. Potential cases were either adjudicated from medical records by experts blind to exposure status, or were identified using electronic data case definition algorithms.

The first study to be published was performed using data from children and young adults aged 2-24 years and published in the New England Journal of Medicine on November 1, 2011.² FDA's recent Drug Safety Communication (DSC) on the child and young adult study can be viewed here.

The study performed in adults included one study that evaluated heart attacks and sudden deaths in a sample of adults, and a second study that assessed strokes in these adults. The adult study is being published in the Journal of the American Medical Association on December 12, 2011.¹

The two adult studies consisted of data from 150,359 current users of ADHD medications and 292,540 non-users. For the combined (composite) outcome of stroke plus MI plus sudden cardiac death, there were a total of 107,322 person years of ADHD drug exposure among current users and 234 events, a much higher rate than in the youth study, as would be expected in an adult population. In comparison to no use, current use of ADHD drugs by adults did not increase the rate of serious cardiovascular events (adjusted incidence rate ratio 0.83, 95% confidence limits 0.72-0.96). Although the rate was lower with ADHD drug use versus no use, due to limitations of the observational study design, we are not concluding that ADHD drugs have a protective effect. An analysis with past ADHD drug users as the comparison group also found no significant increase in cardiovascular events with ADHD drug use, but could not rule out a small increase in cardiovascular risk (adjusted rate ratio 1.03, 95% confidence limits 0.86-1.24).

With this communication, FDA is providing the Agency's analysis of the most up-to-date information that is currently available to healthcare professionals and families.

References

Habel LA, Cooper WO, Sox CM, et al. ADHD medications and risk of serious cardiovascular events in young and middle-aged adults. JAMA 2011 (published online December 12, 2011; doi: 10.1001/jama.2011.1830).
Cooper WO, Habel LA, Sox CM, et al. ADHD drugs and serious cardiovascular events in children and young adults. N Engl J Med 2011. ePub ahead of print. http://www.nejm.org/doi/full/10.1056/NEJMoa1110212 . Accessed November 4, 2011.

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