Large research gap exists in effectiveness, mechanism and safety of drugs in children

Only a few anti-spasticity medications used for children with cerebral palsy are backed by sufficient research to justify their use, according to a new review of scientific literature headed by a UT Southwestern Medical Center neurologist and conducted by a national panel of interdisciplinary experts nationwide.

The findings prompted the American Academy of Neurology to release a new practice guideline on effective treatments. Dr. Mauricio Delgado-Ayala, professor of neurology at UT Southwestern is lead author of the guideline, which appears in the Jan. 26 issue of the academy's journal, Neurology.

Botulinum toxin type A, sold under the brand names Botox and Dysport, is effective and generally safe to relieve spasticity, the researchers found. The drugs diazepam (Valium) and tizanidine (Zanaflex, Sirdalud) can also be used, although they carry more risks.

The researchers found insufficient evidence on whether other commonly used drugs are effective or safe.

A statement by the academy said that practice guidelines are intended to keep neurologists up to date on clinical research and improve medical treatment; they are not intended as hard-and-fast rules.

"The guideline identified a need for more research on most drugs used to treat generalized spasticity," said Dr. Delgado-Ayala. "These drugs might work and be safe, but that needs to be proved.

The lack of evidence does not mean that existing treatment methods are not effective and safe, but it should make us pause and realize that more research needs to be conducted."Most of the medications we use in children were originally studied in adults," Dr. Delgado-Ayala said. "We need to know more about how these medications work in the body, and the doses for best results and least side effects, not only to reduce spasticity but also to improve quality of life."

About 10,000 babies a year in the U.S. are born with cerebral palsy. Cerebral palsy comprises several types of movement disorders, sometimes accompanied by learning disorders, epilepsy and other conditions. The most common characteristic is spasticity, in which muscles tense and flex uncontrollably.

Botox and other drugs can be legally prescribed to treat spasticity, but this use is considered "off-label" because they have not been specifically approved by the Food and Drug Administration for that condition.

For the practice guideline panel, the American Academy of Neurology enlisted five pediatric neurologists, two developmental pediatricians, one pediatric physiatrist, one pediatric orthopedist and one adult neurologist. The panelists examined 218 research studies, all of which appeared in peer-reviewed journals and involved cerebral palsy patients under the age of 19, with at least nine patients studied. The panel made recommendations according to the level of evidence found.

Overall, the literature review identified a large "research gap," showing that the effectiveness, mechanism and safety of many drugs has not been adequately studied in children, Dr. Delgado-Ayala said.

"There is an urgent need to develop new drugs to treat spasticity in general," he said. "There has not been a new drug approved for spasticity by the FDA in more than 10 years."