Evidence-Based Reviews

From a trickle to a flood: Pipelines fill with psychotropics for children

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Pediatric prescribing stands to gain as pharmaceutical companies develop new indications and drugs for younger patients.


 

References

Most psychotherapeutic drugs have been studied only in adults and are not approved for use in children and adolescents. Nevertheless, most drugs used in adult psychiatric treatment are widely prescribed to pediatric patients, and prescribing to this young population has increased dramatically (Box).1-3

Without the benefit of efficacy and safety data, one must rely on anecdotal reports and clinical judgment when choosing medications and determining dosages for children and adolescents. That may be changing soon, as more pediatric information is becoming available on psychotherapeutic drugs approved for adults and on agents under development.

Limited industry attention to pediatrics

The evidence gap between adult and pediatric practice4 can be attributed partly to child and adolescent psychiatry lagging behind adult psychiatry in embracing psychopharmacologic treatments. The primary reason, however, has been the pharmaceutical industry’s history of limited interest in studying pediatric populations.

An unprecedented step. In 1986 at Ciba-Geigy, I and colleagues Richard Katz, PhD, Phyllis Landau, MD, and Georges Moroz, MD, began developing clomipramine, the first drug approved in the United States to treat obsessive-compulsive disorder (OCD). Knowing that OCD onset is common in childhood or adolescence, we proposed doing a pediatric study concurrent with the adult studies that would provide the basis for regulatory approval.

Box 1

DESPITE LIMITED DATA, PEDIATRIC USE OF PSYCHOTROPICS IS GROWING

Researchers have documented a dramatic increase in psychotropic prescriptions to children and adolescents in recent years.

Olfson et al1 reviewed national trends across 10 years. They found the overall annual rate of prescription of psychotherapeutic drugs to children increased from 1.4 per 100 children in 1987 to 3.9 per 100 in 1996. Stimulant and antidepressant drug prescriptions mostly accounted for this nearly threefold increase.

Rushton and Whitmire 2 reviewed a North Carolina Medicaid population and found the number of children prescribed stimulants increased from 6,407 in 1992 to 27,951 in 1998; the corresponding numbers for selective serotonin reuptake inhibitor (SSRI) prescriptions were 510 and 6,984. These represent a fourfold and greater than tenfold increase, respectively, across 7 years.

Zito et al 3 reported increases of 1.3- to 3.1-fold for stimulant and antidepressant prescriptions to preschool children (aged 2 to 4) between 1991 and 1995 in three healthcare settings.

This approach was unprecedented and was initially met with considerable resistance. Ultimately, however, Ciba-Geigy included the pediatric study in the drug development program. As a result, clomipramine became the first psychotropic drug to be simultaneously studied—and eventually approved—for children and adolescents as well as for adults.5,6

Clinical development programs at other pharmaceutical companies followed suit when designing studies of selective serotonin reuptake inhibitors (SSRI) for OCD (SSRIs were just reaching the market as antidepressants). In some programs, pediatric studies were done after initial successful studies in adults with OCD. Even so, the industry continued to show little interest in including children and adolescents in routine clinical development of new drugs or in seeking regulatory approval for this population. This changed several years later, thanks to initiatives from the National Institute of Mental Health (NIMH) and the Food and Drug Administration (FDA).

RUPP and beyond

During the 1990s, NIMH convened meetings with the American Academy of Child and Adolescent Psychiatry (AACAP) and others that brought together representatives from academia, government, industry, and clinical practice, as well as patient advocates.7 Attendees discussed the need for new drug development to treat psychiatric disorders in children and adolescents and the obstacles to be overcome for progress to occur. As a result, NIMH in 1996 established Research Units in Pediatric Psychopharmacology (RUPP).

RUPP is a network of centers of excellence in child and adolescent psychopharmacology based in academic medical centers. Its purpose is to provide definitive studies of psychotropic drugs that are being used routinely in children and adolescents and to provide an infrastructure to support complicated multicenter trials. RUPP’s focus is practical, evaluating treatments used in clinical practice.

To date, RUPP has completed and reported the results of two significant studies:

  • a trial of fluvoxamine in anxiety disorders,8
  • and a trial of risperidone in autistic disorder.9
Other studies are under way, and RUPP has advanced the field substantially.

Even so, RUPP has limitations. Its network cannot conduct studies on all psychotropic drugs that are in use today, and it is not positioned to evaluate investigational drugs (in development but not yet approved).

As a result, RUPP’s network can only partially satisfy psychiatrists’ need for information to guide the prescribing of psychotropics to children and adolescents.

FDA initiatives. Concurrent with the NIMH efforts, the FDA implemented the Pediatric Rule of 1994, which applied to all classes of drugs that might be used in younger patients. Under this rule, pharmaceutical manufacturers:

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