Psychopharmacologic Medication: What Teachers, Clinicians, and Parents Need to Know

Psychopharmacologic Medication:What Teachers, Clinicians, and Parents Need to Know

Four major classes of medications are commonly used to treat children with learning or behavioral disorders: stimulant medications, antidepressants or mood stabilizers, antipsychotics, and anticonvulsants. In addition, anxiolytics (e.g., Valium) and adrenergic agents (e.g., clonidine) are occasionally used to treat some disorders.

Research estimates suggest that between 2% and 3%of all school children may be on one of these medications at any time. • It has been further estimated that between 15% and 20% of children in special education may be receiving one or more of these drugs.

The use of psychopharmacology in treating children and adolescents with a variety of problems and psychiatric diagnoses has increased significantly in the 1990s (Campbell & Cueva, 1995). • This increase is attributed in particular to the expansion of the definitionof attention-deficit disorder in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV; 1994) to includeindividuals without impulsivity or hyperactivity.

PSYCHOSTIMULANTS • The psychostimulants methylphenidate (Ritalin), dextroamphetamine sulfate (Dexedrine), and magnesium pemoline (Cylert) are among the most commonly prescribed and most controversial medications in child psychiatry. • Nearly 2% of the school-age population receives stimulant medication for attention-deficit/hyperactivity disorder (ADHD) symptoms despite concerns about abuse and addiction. • A decrease in classroom performance among children treated with psychostimulants for ADHD and disruptive classroom behavior, questioned whether the resultant decrease in behavior problems or relative gains in attention are worth the greater loss of learning performance in some children. However, Forness and Kavale (1988) and Forness et al. (1992) have also noted the potential efficacy of these drugs across a wide range of classroom functioning for many children.

PSYCHOSTIMULANTS (cont’d) • The only uses approved by the Food and Drug Administration (FDA) for these drugs in children and adolescents are for ADHD and narcolepsy. However, current prescription studies indicate that psychostimulants are also being prescribed to treat ADHD symptoms co-existing with mental retardation, Fragile X syndrome, pervasive developmental disorders (PDD), or autism, organic brain disease, and Tourette's syndrome. All stimulant treatment for such disorders should nonetheless be considered experimental and be closely monitored by the prescribing physician relying on behavioral observations from parents and teachers.

Table 1. Time of Onset and Half-Life for Psychostimulants

Table 2. Psychostimulant Characteristics

ANTI DEPRESSANTS/ MOOD STABILIZERS • Antidepressants or mood stabilizers are quickly becoming the second most often prescribed psychotropic drugs for children and adolescents. • . Antidepressants are not only used to treat depression but also ADHD, obsessive- compulsive disorder (OCD), and school phobia (Werkman, 1993). Four different types of mood stabilizers will be discussed: tricyclic antidepressants (TCAs), novel (atypical) antidepressants, lithium, and monoamine oxidase inhibitors (MA0Is).

Tricyclic Antidepressants • TCAs have been found effective for treating major depressive disorders, anxiety disorders, and panic disorders in adults. • Most are relatively safe, effective, and easy to administer. • Within children and adolescents, however, they have not proven as effective • TCAs are metabolized more rapidly in children and adolescents than in adults. • The only FDA-approved indications for the use of TCAs with children and adolescents is for the treatment of enuresis. However, current research and practice suggests that TCAs may also be indicated for generalized depression, school phobia, and OCD in both children and adolescents. • The administration of TCAs alone or in combination needs to be closely monitored and supervised. In particular, a few case reports have documented sudden unexplained deaths among children taking desipramine, although these events are extremely rare and factors other than the medication itself may be at issue. • No set guidelines exist for dosing patterns or duration of treatment in children and adolescents.

Table 3. Characteristics of Tricyclic Antidepressant (TCAs)

Novel Antidepressants • The novel or atypical antidepressants include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil), also known as selective serotonin reuptake inhibitors (SSRIs). This category also includes bupropion (Welbutrin) and trazadone (Desyrel).

Bupropion and trazadone, although not chemically related to TCAs or SSRIs, have proven effective in the treatment of depression in adults. • Of these, Prozac has become the drug of choice in treating adults because of its relative lack of side effects and withdrawal symptoms. • In general, all the SSRIs have fewer side effects than the TCAs • are more selective in their chemical action • thereby reducing possible negative side effects. • All three of the SSRIs approved for use in the United States begin to work within 2 to 4 weeks, with Prozac having the longest half-life. • There are no currently established indications for the use of SSRIs in the treatment of children and adolescents

Table 4. Most Commonly Prescribed TCAs

When used in combination with TCAs, SSRIs appeared effective, with few side effects in the treatment of childhood anxiety disorders. • Tierney, Joshi, Llinas, Rosenberg, and Riddle (1995) reported that although some children with major depressive disorders (MDD) responded well to sertraline, adverse behavioral effects were common. • Among the other atypical antidepressants approved for use in the United States, it should be noted that trazadone is usually not recommended for routine use with children and adolescents. • Bupropion, on the other hand, has been used to treat ADHD and is being used experimentally in the treatment of MDD in children and adolescents, either alone or in combination with other medications (Barrickman et al., 1995; Campbell & Cueva, 1995; Jensen, 1993). • Bupropion is not FDA approved for use with patients under the age of 18, but it has been used in youngsters with ADHD or MDD who have not responded to treatment with SSRIs or TCAs.

Table 5. Time of Onset and Half-Life for Novel (Atypical) Antidepressants (SSRIs)

Table 6. Characteristics of Novel (Atypical) Antidepressants (SSRIs) Given the extensive list of absolute and relative contraindications for bupropion, we suggest that it be used in children and adolescents only in relatively controlled settings.

Table 6.Characteristics of Novel (Atypical) Antidepressants (SSRIs) Table 7. Characteristics of Other Atypical Antidepressants Given the extensive list of absolute and relative contraindications for bupropion, we suggest that it be used in children and adolescents only in relatively controlled settings.

Lithium • Lithium is also being used to treat some psychiatric disorders of children and adolescents. • Although its only established indication is for the treatment of bipolar disorders in patients over the age of 12, lithium has also been used in combination with other antidepressants for depression that seems resistant to standard treatment. • Campbell et al. (1995) found lithium to be effective in the treatment of severely aggressive children with conduct disorders. • Alessi, Naylor, Ghaziuddin, and Zubieta (1994) noted that lithium also proved effective in treating childhood aggression and behavior disorders associated with mental retardation and other developmental disorders such as autism.

Although GI problems are the most common side effects of lithium treatment: • eye irritation • cardiovascular problems • thyroid problems • diabetes • hair loss • and growth and development delays have also been reported. • Like the other classes of medication reviewed here, dosing levels and intervals for lithium have not been established when used to treat children and adolescents. • Thus, best practice again suggests that treatment with lithium needs to be closely supervised, with blood levels monitored regularly to determine the most effective dosage.

Monoamine Oxidase Inhibitors • As one of the first types of antidepressants developed, MAOls have been researched for 50 years. • Currently, no MAOI is approved for psychiatric use in children less than 16 years old. • Over the years, they have fallen into disuse because side effects such as liver failure and hypertensive crisis have been associated with their use and as newer antidepressants have been developed. • Patients on these medications also have to follow a restricted diet because foods such as cheese or yeast may cause severe or life-threatening drug interactions.

ANTI PSYCHOTIC/ NEUROLEPTIC AGENTS • The antipsychotic agents, also called neuroleptics or major tranquilizers. • Are a primary mode of treatment in adults with psychotic symptoms. • However, because of concerns over possible severe neurological and developmental aftereffects with long-term use and the possibility of short-term side effects that may hamper socialization and learning, only seven agents have FDA approval for use with children younger than 12 years of age (Baldessarini & Teicher, 1995; Forness et al., 1992; McClellan & Werry,1994). • These medications are increasingly being used to replace more costly behavioral interventions as a way of controlling a wide range of disruptive or aggressive disorders and self-injurious behavior in school settings (Campbell & Cueva, 1995; Wilens et al., 1995). • In addition to the established indications, neuroleptics are also used experimentally in the treatment of PDD and some autistic behavior. Trials with such populations have yielded mixed results, and the efficacy of treatment has not been clearly established.

In research focusing specifically on childhood-onset schizophrenia, several new atypical neuroleptics such as clozapine and risperidone have shown promising results, with relatively few side effects reported when treating children and adolescents (Frazier et al., 1994; Quintana & Keshavan, 1995). • These medications seem to relieve not only the positive or active symptoms of schizophrenia such as agitation, delusions, or hallucinations. • Also the so-called "negative" symptoms, such as withdrawal, flat affect, and cognitive dulling, that do not respond as well when treated by more traditional neuroleptics. • Many of the side effects associated with traditional neuroleptics are also minimized with these newer drugs. • Initially, clozapine was restricted to use in patients over 16 years of age and was only indicated when the patient had failed to respond to other traditional neuroleptics. • Another atypical neuroleptic, olanzapine, has proven promising in reducing both positive and negative symptoms with few side effects. • More recent studies have found these atypical neuroleptics effective in treating' aggression, self-injury, explosivity, and overactivity in older adolescents diagnosed with autism, such that they are rapidly becoming the treatment of choice for psychiatric conditions that have failed to respond to first-line neuroleptics, such as Mellaril or Haldol.

Table 8. Characteristics of Lithium

Table 9. Characteristics of Monoamine Oxidase Inhibitors (MAOIs)

ANTICONVULSANTS • The fourth class of medication are the anticonvulsants, which are primarily used in the treatment of epileptic disorders. • Recent research has indicated that anticonvulsants are also useful in the treatment of some behavioral disorders (Rosenberg et al., 1994). • Although anticonvulsants have been used experimentally to treat mood disorders, aggression, and impulse control disorders, the anticonvulsants of choice have changed over the years. • Current best practice employs Tegretol or Depakene when treating behavioral disorders with anticonvulsants.

Table 10. Characteristics of Antipsychotic (Neuroleptic) Agents

Table 11. Characteristics of Anticonvulsants

Anticonvulsants are currently being used in the treatment of bipolar disorders, major depression, and aggressive behavior in children and adolescents. • The efficacy of treating these problems in this population is still under study. • The use of anticonvulsants alone or in combination with other psychoactive drugs for the treatment of nonepileptic disorders needs to be closely controlled and monitored.

ANXIOLYTIC/SEDATIVE AGENTS • Originally developed for the treatment of anxiety disorders. • Anxiolytic (antianxiety) and sedative agents are among the most frequently prescribed drugs. • In children and adolescents, antidepressants are the long-term treatment of choice for most anxiety disorders. • Likewise, antipsychotics and adrenergic agents (clonidine) are often prescribed to children and adolescents for their sedative and antianxiety properties. • Thirty years ago this category of drugs included barbiturates, benzodiazepines, and sedating antihistamines. • Today the term anxiolytic is nearly synonymous with the benzodiazepines, even though antihistamines continue to be used as hypnotics. • A new category of nonsedating, nonaddictive anxiolytic (a • zapirones) has recently been introduced, including buspirone. • Despite having no FDA approved indications for use with persons younger than 18 years of age, the use of buspirone with children and adolescents is of great interest to child psychiatrists because of its minimal sedation and low potential for abuse (Keltner & Folks, 1993; Rosenberg et al., 1994). I

Benzodiazepines • Since chlordiazepoxide (Librium) and diazepam (Valium) were first introduced in the 1960s, the benzodiazepines.(BZPs) have become the most widely prescribed psychoactive agents in the world. • The BZPs are easy to use, have relatively low toxicity, and are highly effective in reducing anxiety. • However, these same qualities have caused the BZPs to become one of the most widely abused prescription drugs, prompting some states to require mandatory triplicate prescription regulations. • Some of the BZPs have been approved for pediatric use, but controlled studies of their efficacy in children and adolescents are scarce. • The BZPs most often used to treat adolescents with anxiety disorders include Xanax, Klonopin, and Ativan. • Because the relationship between BZPs and birth defects has not been clearly established, appropriate contraception should be ensured in adolescent girls of childbearing age.

Antihistamines • Antihistamines are primarily used to treat insomnia due to their mild, rapid sedating effect. • There is no evidence supporting this use to treat anxiety disorders in children, although some evidence suggests that they may be useful as brief treatments for situational or anticipatory anxiety. • Because antihistamines may increase the effects of alcohol and other prescription or illicit drugs, they should be prescribed for adolescents with caution. • All of the anxiolytics are used infrequently with children and adolescents because the tricyclic and novel antidepressants have demonstrated better efficacy with fewer side effects in the treatment of anxiety. • Anxiolytics continue to be used to treat specific psychiatric disorders, including certain sleep disorders and panic disorders. All such uses should be considered short-term interventions, however, because tolerance to the sedative properties develops quickly and all of the anxiolytics may predispose patients to drug abuse.

ADRENERGIC AGENTS • The two adrenergic agents to be considered here are the antihypertensive clonidine and the beta-blocker propranolol. • Adrenergic,agents influence the secretion or absorptionof adrenaline and noradrenaline. • When adrenaline ornoradrenaline levels are determined to be low, adrenergic agents are used to increase the secretion of these substances. • When the levels of adrenaline or noradrenaline are determined to be adequate but are not being absorbed at receptor sites, adrenergic agents are used to increase absorption. • Adrenaline or noradrenaline are central nervous system neurotransmitters that are involved in blood pressure regulation, cardiac output, and arousal. • Neither of the adrenergic agents considered here are approved by the FDA for treatment of psychiatric disorders but are often routinely prescribed for treatment of several disorders that fail to respond to other forms of medication or to reduce side effects of other medications.

Clonidine • Clonidine (Catapres) is an antihypertensive with no established FDA recommendations for use in child and adolescent psychiatry. • Clonidine has been investigated most often as a treatment for Tourette's syndrome, although there is a recent trend toward treating this disorder more often with certain novel antidepressants. • It has also been used to treat ADHD in children and adolescents, especially when conventional stimulant medications are not effective. • Further, clonidine has been used in clinical trials for the treatment of anxiety and panic disorders, bipolar disorders in children and adolescents, psychosis, agitation, ADHD in adults, borderline personality disorder, social phobia, conduct disorders, mania, autism, and posttraumatic stress disorder. • These trials have suggested that clonidine is more effective in reducing hyperarousal and motor activity and less effective in decreasing distractibility and improving attention span (Hunt, Capper, & O'Connell, 1990). • Clonidine is sometimes used in combination therapy with Ritalin in the treatment of ADHD.

Table 12. Anxiolytic Characteristics

Table 13. Available Benzodiazepines, Their Age Range, and Plasma Half-Life in Adults

Table 14. Available Antihistamine Agents

Propranolol • Propranolol (Inderal) is a nonselective beta-adrenergic blocking agent with manyestablished uses for treatment of cardiovascular disorders but no FDA-established indications for use in psychiatric disorders. • Investigative studies have suggested that propranolol may be effective in reducing aggression in patients with brain damage and in the treatment of posttraumatic stress disorders, anxiety and panic disorders, and motor restlessness (Rosenberg et al., 1994). • Propranolol is also used to treat behavior disorders in some children with mental retardation when other first-line agents have failed. • Because the efficacy andsafety of propranolol have not been established in children and adolescents with psychiatric disorders, its use should be considered investigative when prescribed to these populations. • Propranolol is metabolized by the liver, and in adults exerts its peak effect 1 to 1 1/2 hours after oral administration. It has a serum half-life in adults of between 3 and 6 hours, so it must be given more than once per day. • Due to the potential life-threatening side effects of propranolol (e.g., asthma and congestive heart failure), a complete medical history and physical examination should be completed before beginning treatment. • None of the other beta-blockers (e.g., atenolol, nadolol, or metoprolol) are currently indicated for use with children or adolescents.

Table 15. Clonidine Characteristics

Table 16. Propranolol Characteristics

ETHICAL AND LEGAL CONCERNS • Despite substantial advances over the past several years, the field of pediatric psychopharmacology is faced with several ethical, methodological, and regulatory issues that remain unresolved (Biederman, 1996). Glantz (1996) pointed out that several ethical issues surround the use of psychotropics with children and adolescents in the absence of sufficient data to support their use, including the inability to obtain informed consent from minor or incapacitated subjects and the risk of using placebo in patients with a known illness. • Until recently, no large-scale studies had investigated the efficacy of psychotropic medications in the treatment of psychiatric illnesses in children and adolescents (Greenhill et al., 1996). This lack of research has contributed to the absence of FDA approval for the use of many psychotropic agents with children and adolescents, which requires that the safety and effectiveness of each medication be adequately demonstrated within each age group for each condition indicated (Laughren, 1996). • Issues to be considered in such clinical trials include drug effects on growth and development and onset of potentially dangerous side effects. • Current FDA regulations do not require pharmaceutical companies to conduct research in pediatric populations prior to bringing a new drug to market; therefore., little funding is available for such studies. • Some professionals are becoming more concerned that this increased reliance on psychopharmacology represents a trend in which quality programming for children and adolescents with emotional or behavioral disorders is being replaced by attempts to find a quick cure to behavior problems through the use of medication (Forness, Sweeney, & Toy, 1996). However, Gadow (1992) noted that advances in pharmacology have provided better information about dosing levels, concentration of the drug at the effector site, and the end response. • As a result, many drugs may be used selectively to treat psychiatric symptoms or behaviors not previously thought to respond to these medications. For example, antidepressants and neuroleptics are sometimes used to treat certain disruptive behavior disorders (Rosenberg et al., 1994).

Psychopharmacologic Medication: What Teachers, Clinicians, and Parents Need to Know