For release: Tuesday, April 2, 2002
For decades, doctors who have treated children with both attention deficit-hyperactivity disorder (ADHD) and tics have been warned not to prescribe methylphenidate (Ritalin), the most common drug for ADHD, because of a concern that it would make the tics worse. Now, the first randomized, placebo-controlled clinical trial of methylphenidate and another drug, clonidine (Catapres), has found that in fact these drugs do not adversely affect tics. The researchers also found that a combination of the drugs is more effective than either drug alone.
The study showed that methylphenidate and clonidine are individually effective for treating ADHD in children with tics and that the two drugs help control different symptoms of ADHD, says Roger Kurlan, M.D., of the University of Rochester Medical Center in New York, who led the multicenter study. Methylphenidate primarily improved attentiveness and helped children stay "on task," while clonidine helped control hyperactivity and impulsivity. The study was supported in part by the National Institute of Neurological Disorders and Stroke (NINDS).
Most experts estimate that ADHD affects between 2 and 5 percent of children in kindergarten through grade 12, although some studies have suggested that those estimates are low. In Rochester, about a third of the children with ADHD also have tic disorders, although the tics in some children are very mild, Dr. Kurlan says. Studies have tied both ADHD and tics to problems in the brain's basal ganglia and in connections between the basal ganglia and the frontal lobes, which may explain why the two disorders often appear together, he adds.
The study examined the effects of methylphenidate alone, clonidine alone, methylphenidate plus clonidine, and a placebo in 136 children aged 7 - 14 years who had been diagnosed with both ADHD and a chronic tic disorder, such as Tourette syndrome. The investigators adjusted the doses of the drugs to achieve the best results in each child. Each patient's symptoms were rated by the study investigators and by his or her parents and a designated teacher at various points during the 16-week study period. An independent observer also rated classroom behavior at the beginning and end of the study.
Children who received methylphenidate or clonidine alone had significantly fewer ADHD symptoms than children who received the placebo, the study found. However, children who received both drugs did the best of all the groups. While some children's tics worsened initially, this change also occurred in the placebo group, suggesting that it was not caused by the drugs. By the end of the study, tic severity actually decreased in all of the children who received drug treatment, with the best results in the children who received both drugs.
About half the children who received clonidine alone experienced sedation (drowsiness), which was the most common side effect in this study. However, this problem was less common in children who received the combination therapy.
Because there had been previous anecdotal reports of sudden death and heart problems in several children who received combined treatment with methylphenidate and clonidine, the researchers excluded children with pre-existing heart problems from this study and then looked closely for evidence that the drugs affected children's hearts. They did not find any heart problems that resulted from treatment with the individual drugs or the combination therapy. One patient on clonidine developed a heart arrhythmia, but it was so mild that the patient did not notice any symptoms, says Dr. Kurlan. However, more study is needed to determine if the drugs are safe in children with pre-existing heart problems.
This is the first study to examine the safety and effectiveness of combined treatment with methylphenidate and clonidine in children with both ADHD and tics, although some previous studies tested methylphenidate alone with mixed results, the investigators say. Use of the combination therapy has been increasing in recent years and investigators suspected that the reported tic-suppressing effect of clonidine might counteract the apparent tic-accentuating effect of methylphenidate.
While this study focused on children with both ADHD and tics, the differing effects on ADHD symptoms in children treated with methylphenidate or clonidine alone suggest that clonidine may be an alternative to methylphenidate for children with ADHD who primarily have hyperactivity, says Dr. Kurlan. It also may be helpful for children who have a combination of symptoms, he adds. For children whose primary symptom is inattention, however, methylphenidate appeared to be a better option.
The researchers are now planning clinical studies of a drug called guanfacine, which is similar to clonidine but appears to cause less sedation, to see if it has the same beneficial effects as clonidine for these children. They also plan to test longer-acting versions of methylphenidate and other types of stimulants, such as dextroamphetamine (Dexedrine) and a combination of amphetamines (Adderall), to see what effect those drugs have on tics in children with ADHD.
Reference: The Tourette's Syndrome Study Group. "Treatment of ADHD in children with tics." Neurology, Vol. 58, No. 4, February 26, 2002, pp. 527-536.
Editorial: Nass R, Bressman S. "Attention deficit hyperactivity disorder and Tourette syndrome: what's the best treatment?" Neurology, Vol. 58, No. 4, February 26, 2002, pp. 513-514.
- By Natalie Frazin
Last Modified September 30, 2011