In September 2005, the U.S. Food and Drug Administration (FDA) issued a warning that atomoxetine (Strattera) — a treatment for attention-deficit hyperactivity disorder (ADHD) — may increase suicidal thinking in a small percentage of children and adolescents.
The warning labels advise parents and guardians to call a doctor immediately if the child develops thoughts of suicide, or if the child's mood changes for the worse.
During that period, the FDA looked closely at the effects of psychiatric drugs on the risk of suicide, particularly in children and adolescents. In a review of 2,200 cases of children and adolescents taking either atomoxetine or placebo (sugar pill), evaluators found that approximately one in every 250 patients taking atomoxetine reported suicidal thinking. One patient taking the drug made a suicide attempt. No one in the placebo group reported suicidal thoughts or behavior.
None of the subjects in either group committed suicide. Nonetheless, given the difference between the drug and placebo groups, the FDA recommended being cautious. That is, the need for the drug should be balanced against serious risks.
Atomoxetine carries another rare, but important risk: Two cases of severe liver damage have been reported. Though both patients recovered when they stopped taking the drug, in 2004 the FDA issued an advisory about that risk.
To put this in perspective, though, more than 2 million patients have taken atomoxetine. To be safe, anyone taking the drug should look out for the symptoms of liver damage, including itching, dark urine, jaundice (yellowing of the skin), or some discomfort on the right side of the belly (where the liver is).
Stimulants such as methylphenidate (Ritalin and others) and amphetamine have been the first choice for treating ADHD for almost 75 years. They are believed to work by boosting the transmission of chemical messengers in the brain, primarily norepinephrine and dopamine. Dopamine is the chief neurotransmitter in the motor and reward systems, which explains why the drugs enhance a child's level of attention. But it also explains two occasional but troubling side effects: tics and substance abuse.
Atomoxetine is as effective for treating ADHD as are stimulants, but it achieves its effect by a different mechanism. Atomoxetine increases the activity of norepinephrine by blocking the pump that pulls it back into nerve cells. Atomoxetine does not affect dopamine concentrations. The drug is therefore classified as a selective norepinephrine reuptake inhibitor (SNRI). Other antidepressants that boost norepinephrine are also effective for ADHD, such as tricyclics (amitriptyline and imipramine) and bupropion (Wellbutrin).
Because atomoxetine doesn't activate dopamine, it doesn't affect the reward system, which means people won't abuse it. Atomoxetine also does not have the uncomfortable and sometimes dangerous side effects of tricyclic antidepressants. Thus, atomoxetine is an important alternative to older treatments.
Nausea, vomiting, stomach distress, loss of appetite, weight loss, weakness and fatigue are the most common side effects of atomoxetine in children. In adults, sexual problems can occur, and some patients develop trouble starting their urinary stream. A rise in pulse or blood pressure is a concern for those with heart disease or cerebrovascular disease, though these measurements usually return to normal when the drug is stopped. Overall, however, atomoxetine is tolerated reasonably well.
Despite these concerns, atomoxetine will remain one of the therapies for ADHD, a condition that affects up to 1 in 10 school-age children. In fact, for patients who are vulnerable to drug abuse or who have not been able to tolerate treatment with stimulants, atomoxetine may be the best and even the safest option.
People respond differently to medications, so it is always important to weigh the personal advantages of atomoxetine against risks small and large. Suicide, like liver failure, is a terrible result, but fortunately suicide is very rare.
Close follow-up and regular meetings with the doctor are always important. Call the doctor immediately if you have any questions about your or your child's progress. If you and your doctor stay alert to the warnings, you or your child can still have the benefit of the drug while significantly reducing the risks.
Michael Craig Miller, M.D., is the Editor in Chief of the Harvard Mental Health Letter. He is also associate physician at Beth Israel Deaconess Medical Center and assistant professor at Harvard Medical School. He has been practicing psychiatry for over 25 years at Beth Israel Deaconess Medical Center. He teaches in the Harvard Longwood Psychiatry Residency Program.