Pediatric Indications for CNS Disorders

Behavioral disorders in the pediatric population account for as many as 20% to 25% of office visits to a general pediatric practice.¹ It was once perceived that many psychiatric disorders, such as depression, bipolar disorder, obsessive compulsive disorder, and anxiety disorder, only manifested themselves in the adult population. More recently, it is estimated that 1 in 10 children and adolescents in the United States suffers from some form of mental illness causing some level of impairment.¹ Furthermore, fewer than 1 in 5 of these children receives any treatment at all.¹

Today, many treatments are available for children who have either behavioral or learning disorders, and may include both the use of medications and behavioral therapy. Each therapy should always be individualized based upon each patient's specific need. Childhood-onset depression and anxiety disorders are increasingly recognized and treated.² Attention deficit-hyperactivity disorder (ADHD), however, is the most studied, diagnosed, and treated childhood-onset psychiatric disorder. Yet, even this disorder has a need for further research with respect to very young children.³ The American Academy of Pediatrics (AAP) estimated an incidence of ADHD in children of between 4% and 12%.¹

Another condition that is on the rise is autism. Autism is a complex developmental disability that affects an individual in the areas of social interaction and communication in various degrees of severity. It affects 1 million to 1.5 million individuals in the United States and is considered to be the fastest growing developmental disorder.⁴

Pharmacologic Agents

Great debate still exists among many health care professionals regarding the best treatments for children with behavioral or learning disorders. It is quite evident that more studies need to be conducted, since the numbers of children with behavioral and learning disabilities continue to increase. Until more clinical research is done on the safety and efficacy of these agents with regard to the pediatric population, health care professionals will continue to debate whether it makes sense to prescribe these medications to the pediatric population.

The primary considerations when using medications in children include appropriate dosing, frequency of dosing intervals, distribution, metabolism, excretion of the drug, adverse effects, and long-term effects associated with their use. Common indications in which central nervous system (CNS) agents are used in children include:

• Anxiety and depression
• Behavioral problems
• Seizures?occuring in 1 in 4 individuals with autism spectrum disorder (ASD)⁴
• Hyperactivity and attention deficit

Psychostimulant Medications

Psychostimulants are generally the first line of therapy in treating children with ADHD (Table 1). They are the most commonly prescribed medications for the treatment of ADHD. It is thought that they exert their therapeutic effect by blocking the reuptake of norepinephrine and dopamine into the presynaptic neuron and increasing the release of these monoamines into the extraneuronal space.⁵

Nonstimulant Approved for ADHD

Amoxetine is the first noncontrolled, nonstimulant drug approved by the FDA to treat ADHD. The precise mechanism by which atomoxetine produces its therapeutic effects in ADHD is unknown, but is thought to be related to selective inhibition of the presynaptic norepinephrine transporter, as determined in ex vivo uptake and neurotransmitter depletion studies.⁶ Amoxetine is dosed once or twice a day. Common adverse effects include sleep disorders, stomach upset, and dizziness.

Antidepressants and Antianxiety Agents

Antidepressants

Selective serotonin reuptake inhibitors, such as fluoxetine, paroxetine, and sertraline, are the second-most prescribed psychotropic medications, after stimulants, for children.⁷ They are utilized to treat severe and persistent depression and anxiety disorders such as obsessive-compulsive disorder (OCD). In January 2003, the FDA approved the use of the antidepressant Prozac (fluoxetine) to treat children and adolescents 7 to 17 years of age for depression (major depressive disorder) and OCD.⁸ It is the only antidepressant that is FDA-approved for the treatment of major pediatric depression. On December 2, 2003, the Pediatric Research Equity Act of 2003 was signed into law. This Act provides the FDA with the authority to require drug manufacturers to perform pediatric testing on drugs and biological products, in order to establish safety and efficacy in children.⁹ More recently, in March 2004, the FDA asked pharmaceutical companies to include a stronger warning label with a recommendation of close observation of both adult and pediatric patients receiving antidepressants for worsening of depression or suicidality, particularly at the beginning of therapy or during dosage changes.¹⁰ The medications included in this new warning are: Prozac, Zoloft, Paxil, Luvox, Celexa, Lexapro, Wellbutrin, Effexor, Serzone, and Remeron. No cases of suicide have been found in the more than 4000 cases studied.¹⁰ The warning also encourages health care providers to carefully monitor patients throughout therapy. Other antidepressants used in children include the tricyclics (Table 2).

Antianxiety Agents

Anxiety is the most common mental health problem that occurs in children. Children are most often treated with benzodiazepines such as clonazepam and diazepam.⁷

Antipsychotic Agents

Antipsychotic agents (Table 3) have been used to treat various psychotic disorders, but have also been utilized to control severe symptoms, such as agitation, aggression, and self-injurious behaviors sometimes seen in children with severe developmental disorders or pervasive developmental disorders such as autism.⁷

Mood-Stabilizing Agents

These medications (Table 4) are sometimes used to treat bipolar disorder (manic-depressive illness). Because very limited data exist on the safety and efficacy of most mood stabilizers in youth, however, treatment of children and adolescents is based mainly on experience with adults.⁸

Role of the Pharmacist

Pharmacist have the responsibility to ensure that all medications are used appropriately, especially in the pediatric population due to the differences in the pharmacokinetics of this specific patient population. The pediatric patient population requires careful evaluation to determine safe and effective dosages. When the decision to place a child on a medication is made, it is essential that there be consistent monitoring by both the physician and caregiver to assess the patient for therapeutic and adverse effects. Consideration should also be given to incorporating nonpharmacologic therapies, such as behavior modification, and other forms of therapy, including support groups or educational programs geared toward specific behavioral disorders. Pharmacists should counsel all caregivers of children on medication about all pertinent patient information regarding the use of these medications and the importance of adhering to the therapy as directed; inform them of any potential drug interactions with other medications; and report any adverse effects to their health care provider. The best interest of each child should be the major focus of therapy. Health care providers need to make individualized clinical decisions by weighing the benefits versus the risks of pharmacologic therapy.

For more information, please visit the following Web sites:

National Institute of Mental Health Web site at: www.nimh.nih.gov.

Food and Drug Administration Web site at: www.fda.gov.

Ms. Terrie is a clinical pharmacy writer based in the northern Virginia area.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@ascendmedia.com.