The National Institute of Mental Health (NIMH) has awarded a contract providing almost $500,000 a year jointly to Johns Hopkins University (JHU) and the New York State Psychiatric Institute (NYSPI) at Columbia University to study whether psychotropic drugs approved for adults are safe and effective for children and adolescents.

Although the contract must be renewed annually, researchers from both JHU and the NYSPI said they anticipated that funding would be provided for a total of three years. In addition to the NIMH funds, Solvay Pharmaceuticals agreed to provide $100,000 a year for three years contingent on yearly renewal of the NIMH contract, according to Laurence Greenhill, M.D., an associate professor of clinical psychiatry at Columbia University and principal investigator for the NYSPI site.

The research will be conducted in special units, called Research Units of Pediatric Psychopharmacology (RUPP's), that will be set up at universities and hospitals in Ohio, California, Louisiana, Arkansas, Tennessee, and Michigan. The RUPP's will be networked with the Hopkins and Columbia sites.

Nationwide 8 million children suffer from behavioral and emotional problems each year, according to NIMH. Although clinicians often use psychotropic medication, 80 percent of psychiatric drugs marketed today are not approved for use in children or adolescents, leading to widespread off-label prescribing.

The results of the program will be used to help pharmaceutical companies provide the Food and Drug Administration (FDA) with data on the appropriate use of psychiatric medications in children, said Greenhill.

At present, "pediatricians, child psychiatrists, family practitioners, and pediatric neurologists are doing a lot of off-label prescribing" in treating children with mental disorders, he noted. NIMH thought it was time for "the field [to] catch up to practice so that clinicians will be comfortable prescribing Prozac or other widely used drugs for kids."

Psychotropic drugs approved for adults may have unpredictable side effects when used by children. There have been infrequent reports of sudden death following use of such common drugs as desipramine and clonidine, according to Greenhill. No cause-and-effect relationship has been established between use of these drugs and such fatalities, but the FDA was concerned enough that it issued a directive to manufacturers that packages of desipramine carry a revised package insert warning that it "has been associated with sudden deaths in children," he noted.

NIMH directed the RUPP's to look first at drugs used to treat anxiety disorders in children. One class of drugs getting close scrutiny will be the selective serotonin reuptake inhibitors (SSRI's).

Other studies will look at pharmacotherapy for obsessive-compulsive disorder, major depressive disorder, and pervasive developmental disorders. Attention deficit disorder and comorbid substance abuse are excluded from the RUPP agenda because they are already being adequately researched through the National Institute on Drug Abuse and other agencies and programs, said Greenhill.

The FDA requires that all new drugs be tested for each population in which they will be used, but ethical and methodological obstacles have long hampered drug research in children, according to Mark Riddle, M.D., director of the JHU Division of Child and Adolescent Psychiatry and principal investigator for the Hopkins site.

"Off-label use of psychiatric medications for children and adolescents is very common," Riddle said. This occurs because "very few of the medications used to treat children with psychiatric disorders have been subjected to safety and efficacy studies that meet adequate standards of science. Thus, clinicians who treat children with psychiatric disorders have a difficult choice--either prescribe off-label or withhold medication from children."

The RUPP initiative will "move the field forward," he added. As part of this process, the FDA has revised labeling criteria to make it easier for drug companies to run safety and efficacy studies on children prior to marketing, Riddle said.

Children "really are therapeutic orphans," said Riddle. "In this country, adults are not exposed to new drugs until safety and efficacy studies are reviewed and approved by the FDA." Such data often involve thousands of adults 18 years and older, he noted.

In contrast, "of the last 10 new psychiatric drugs that have come onto the U.S. market, none had any data on safety and efficacy for children," Riddle said.

For clinicians, the situation is like trying to "fly the plane while we are building it," said Riddle. "If that plane were full of adults, there would be no flying until the federal government had carefully evaluated its safety."

The results of the RUPP studies "should be helpful to pediatricians as well as child and adolescent psychiatrists," said Riddle. Pediatricians are increasingly prescribing for those psychiatric disorders more common in children, including ADHD, anxiety, and depression, he noted.

In addition to evaluating safety and efficacy of existing medications for use in children, the "single most important goal that can be realized from the RUPP's is to develop a national infrastructure for pediatric psychopharmacology research," said Riddle. "I hope that some day children with medication-responsive psychiatric disorders, which are often chronic and disabling, will have the benefit of research comparable to that for children with cancer. Children with major psychiatric disorders deserve no less."

(Psychiatric News, May 16, 1997)