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

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Psychopharmacologic MedicationWhat Teachers,
Clinicians, and Parents Need to Know
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• 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.

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• 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.

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• 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 definition of attention-deficit
  disorder in the American Psychiatric
  Association's Diagnostic and Statistical Manual
  of Mental Disorders, 4th Edition (DSM-IV 1994)
  to include individuals without impulsivity or
  hyperactivity.

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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/hyperac
  tivity 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.

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PSYCHOSTIMULANTS (contd)

• 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.

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Table 1. Time of Onset and Half-Life for
Psychostimulants
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Table 2. Psychostimulant Characteristics
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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).

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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.

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Table 3. Characteristics of Tricyclic
Antidepressant (TCAs)

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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).

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• 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

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Table 4. Most Commonly Prescribed TCAs
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• 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.

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

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• 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.

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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.

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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.

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• 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.

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Table 8. Characteristics of Lithium
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Table 9. Characteristics of Monoamine Oxidase
Inhibitors (MAOIs)
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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.

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Table 10. Characteristics of Antipsychotic
(Neuroleptic) Agents
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Table 11. Characteristics of Anticonvulsants

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• 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.

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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

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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.

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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.

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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
  absorption of adrenaline and noradrenaline.
• When adrenaline or noradrenaline 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.

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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.

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Table 12.
Anxiolytic Characteristics
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Table 13. Available Benzodiazepines, Their Age
Range, and Plasma Half-Life in Adults
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Table 14. Available Antihistamine Agents
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Propranolol

• Propranolol (Inderal) is a nonselective
  beta-adrenergic blocking agent with many
  established 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 and safety 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.

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Table 15. Clonidine Characteristics
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Table 16. Propranolol Characteristics
 
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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).