The evidence in support of using the stimulant methylphenidate (more commonly known by such brand names as Ritalin, Concerta, Methylin and Medikinet) to treat children with attention deficit hyperactivity disorder (ADHD) is of such low quality that physicians should prescribe these drugs only with caution, the authors of a major new meta-analysis warn.

The meta-analysis — conducted by an independent and international team of 17 Cochrane researchers — found that the evidence in favor of treating ADHD with methylphenidate is weaker than many physicians (and parents) realize.

Furthermore, even if the existing evidence is taken at face value, the benefits from methylphenidate are modest at best. And the drug is not harm-free, for its use in children is associated with sleep problems and decreased appetite.

The meta-analysis’ findings, published last week in the Cochrane Database of Systemic Review, are troubling. ADHD is one of the most commonly diagnosed and treated childhood neurodevelopmental disorders. In 2011, approximately 11 percent of U.S. children aged 4 to 17 — 6.4 million young people in all — had been diagnosed with ADHD, according to the Centers for Disease Control and Prevention (CDC).

More than half of these children — 6.1 percent of all American children and teens — were taking a medication, primarily methylphenidate, to control their ADHD symptoms, which include difficulty paying attention and controlling impulsive behaviors and/or a tendency to be overly active. 

Details of the review

For their meta-analysis, the Cochrane reviewers looked at 185 studies (38 randomized controlled trials and 147 crossover trials) that compared methylphenidate with either placebo or no intervention. The studies, which were mostly conducted in the U.S., Canada and Europe, involved more than 12,000 children and teens, aged 3 to 18. The children took methylphenidate for one to 425 days, with an average treatment run of 75 days.

A pooling of the data from a number of those trials revealed that methylphenidate resulted in a slight improvement in how teachers rated ADHD symptoms when compared to placebo or no intervention. But the difference was modest: an average of 9.6 fewer points on the ADHD Rating Scale. This scale has a range of 0 to 72 points, and, as experts for the U.K.’s National Health Service note in their discussion of the meta-analysis, a change of 6.6 points is considered the minimal amount needed to be clinically meaningful.

The Cochrane reviewers also say that those modest improvements need to be balanced against an increased risk of adverse effects, particularly sleeping problems and decreased appetite. Their analysis found that children with ADHD who received methylphenidate in clinical trials were 29 percent more likely to develop these problems than children with ADHD who received a placebo.

Although the reviewers found no evidence that methylphenidate leads to serious adverse health problems in children, they point out that “very little” is known about the drug’s long-term effects. That’s because most studies that examined methylphenidate in children did not last longer than six months.

Extensive bias

But the overriding problem with all 185 studies, say the Cochrane reviewers, is that each was designed in a way that could have led to biased findings. In many of the studies, for example, it would have been relatively easy for everybody involved to figure out which children were taking the drug and which were taking the placebo.

In addition, some 40 percent of the methylphenidate studies were funded by the pharmaceutical industry. In recent years, several groups of researchers, including a team from Cochrane, have reported that industry-sponsored studies are significantly more likely to produce results that paint a positive picture of a drug or device than independently funded ones.

The 185 studies “suggest that methylphenidate might improve some of the core symptoms of ADHD — reducing hyperactivity and impulsivity, and helping children to concentrate,” the authors of the meta-analysis conclude.  “Methylphenidate might also help to improve the general behaviour and quality of life of children with ADHD. However, we cannot be confident that the results accurately reflect the size of the benefit of methylphenidate.”

“Better-designed trials are needed,” they stress, before we can know for sure if the benefits truly outweigh the risks.

You’ll find the study on the Cochrane Library website.