Pharmacotherapy as a treatment modality for children and adolescents is a relatively young

discipline that is based more on the collective experiences of clinicians than on empirical
verification of the effects of various classes of psychoactive medications on children's
psychiatric disorders. Because of the paucity of empirical data, pharmacotherapy was
regarded as the treatment of last resort in this population until the mid-1990s. Indeed,
clinicians did not consider it during initial treatment formulation until all other treatment
modalities had been tried.
The situation today, however, is somewhat different. Although there are still few empirically
based studies on the use of psychotropic drugs in the treatment of childhood disorders,
pharmacotherapy is considered, along with other treatment modalities, an integral part of a
treatment plan. Like any other single modality treatment, pharmacotherapy is limited in scope
because it focuses on only one aspect of the child. Given that children develop in an
interactional biological, psychological, social, and cultural matrix, effective interventions
must be multimodal, multifocused, and interdisciplinary in nature.
A comprehensive psychiatric assessment is necessary before a child or adolescent can be
considered for pharmacotherapy. The assessment provides the basis for determining the
child's psychopathological condition, indications for treatment, and the nature of the proposed
treatment. It is multidimensional and interdisciplinary, incorporating assessments of the
child's symptoms and functioning across multiple domains, as well as an evaluation of his or
her family history and physical and cultural environment. Typically, a baseline assessment
includes (a) the source of and reason for referral, including the target symptoms that may be
the focus of treatment, (b) history of the presenting symptoms, (c) psychiatric history and
current mental status, (d) developmental and medical history, (e) family and education/school
history, and (f) an evaluation of cultural context of the family (e.g., determine if the family
has any specific religious, spiritual, or cultural beliefs that may interact with the child's
psychiatric treatment in general and psychopharmacological treatment in particular).
In general, the psychiatrist's goal is to understand the presenting problems or symptoms at the
highest level of diagnostic sophistication that can be achieved based on a comprehensive
interdisciplinary assessment. There are four levels of diagnostic sophistication: (1)
symptomatic, which includes isolated symptoms (e.g., auditory hallucinations) that provide an
indication of a possible diagnosis (e.g., psychotic disorder not otherwise specified), (2)
syndromic, which includes the constellation of signs and symptoms that have been present for
a given time, and standardized inclusionary and exclusionary criteria can be used to derive a
diagnosis (e.g., depression), (3) pathophysiologic, which includes structural or biochemical
changes that indicate the diagnosis (e.g., an individual presenting with anxiety, depression, or
manic excitement, weakness, excessive sweating, tremors, and, in some cases, with
disturbances of thought and cognition may have elevated thyroid function tests that suggest a
diagnosis of hyperthyroidism, and (4) etiologic, in which the diagnosis is based on known
causative factors.
With children, most psychiatric diagnoses are at the symptomatic and syndromic levels of
sophistication because we currently do not have a thorough understanding of the
pathophysiology or etiology of many childhood disorders. Thus, it is not uncommon to find
wide variability in treatment outcomes in children diagnosed with the same syndrome because
they have similar presentations but substantially different underlying mechanisms. This means
that at times we treat children's behavioral symptoms or psychiatric disorders without fully

appreciating the biological and genetic underpinnings or how these factors transact with the
children's physical, psychosocial, and cultural environments.
The clinical formulation follows the standard biopsychosocial model, which means that
biological, psychological, and social factors are integrated into a comprehensive framework
for understanding the child's symptomatic and syndromic presentation. Once the relevant data
are gathered, the clinician synthesizes the information and reaches a working diagnosis.
However, before a psychiatric diagnosis is finalized, any general medical conditions that may
account for the child's problems are ruled out. In addition, it is critical that deviation from the
normal range of development is considered. Furthermore, a child may have symptoms of
multiple conditions and all relevant diagnoses are considered (e.g., attentiondeficit/hyperactivity disorder [ADHD] and learning disorders).
In the clinical formulation for pharmacotherapy, the clinician pays particular attention to signs
and symptoms associated with psychiatric disorders that are biologically based. These
disorders are potentially responsive to psychotropic agents. The clinician obtains much of this
information from a descriptive, phenomenological assessment of the child's feelings,
emotions, and behaviors, which provides important insights on the child's disorder(s).
Because the same signs and symptoms occurring at different ages may be indicative of
different disorders, information on the clinical course helps the clinician to place the disorder
in a specific developmental context. For example, attention and concentration problems may
be indicative of ADHD at ages 5 or 6 but of a mood disorder at 15 or 16. The clinician uses all
of this information to formulate a treatment plan that includes pharmacotherapy as well as
psychosocial and psychoeducational interventions, because pharmacotherapy alone is rarely
sufficient for complete recovery. Medication provides symptomatic relief, allowing the child
to function more fully at school and home and in the community. Furthermore, medication
usually relieves the child's symptoms of psychiatric illness, but it does not address the
vulnerability to its recurrence because the environmental and constitutional stressors that gave
rise to the illness are not affected by the medication.

RESEARCH BASIS
Until very recently, children were thought of as little adults in terms of pharmacotherapy.
Drugs and dosages were extrapolated from the adult research literature to treat childhood
disorders. Pharmacotherapy was based more on the trial-and-error experiences of individual
clinicians than on evidence-based practice derived from randomized controlled trials. Indeed,
in the United States, the Food and Drug Administration (FDA) has not formally approved
many of the drugs currently used by physicians to treat childhood disorders. Using drugs not
approved by the FDA is called off-label use and sometimes leads to questionable
medication management practices.
With the passage of the FDA Modernization Act in 1997, drug companies were encouraged to
conduct pediatric studies of psychotropic agents. In 1998, the FDA passed regulations
mandating that drug companies assess the safety and efficacy of new drugs intended for use
by children. In addition, the National Institute of Mental Health began sponsoring large
multicenter research studies with the Research Units on Pediatric Psychopharmacology
(RUPP) grants. While the evidence-based research data on the safety and efficacy of drugs for
treating childhood disorders are currently very limited, these recent national efforts should
increase our knowledge substantially in the near future.

RELEVANT TARGET POPULATIONS AND

EXCEPTIONS
The target patient populations for pharmacotherapy are defined by the presumed etiology of
the presenting problems of children and adolescents. Additional factors that define these
populations include empirical evidence from randomized controlled trials, other wellcontrolled treatment outcome research, and, to a lesser extent, clinical case studies. When
clearly implicated in the etiology of the disorder, or the presenting problem, psychobiology
and neurobiology may provide rational targets for pharmacological interventions.
Following a complete diagnostic assessment, medication is prescribed adjunctively within an
interdisciplinary psychosocial and psychoeducational plan. Pharmacotherapy is used only
when a child has a medication-responsive psychiatric diagnosis or there is a behavioralbiological rationale for the treatment. For example, aggression associated with an identifiable
psychiatric illness (e.g., psychotic disorder, mood disorder, or mental disorder due to a general
medical condition) may be controlled when the underlying disorder is treated with
medication, but instrumental or predatory aggression, which is associated with low levels of
autonomic nervous system arousal and intended to extract resources from the environment in
a planned and premeditated fashion, may not be responsive to medication.
The major classes of medications used with children include the antipsychotics,
antidepressants, antimanics, anxiolytics, and stimulants. In children, the antipsychotics are
used mainly in the treatment of psychotic disorders, as well as other behavioral symptoms
such as agitation, aggression, self-injury, tics, and stereotypies. Psychotic disorders (e.g.,
schizophrenia) present with positive (or productive) symptoms (e.g., delusions and
hallucinations) and negative (or deficit) symptoms (e.g., blunting or flattening of affect,
poverty of speech and thought, lack of motivation, poor self-care, and social withdrawal).
There are two main classes of antipsychotics: the older or typical agents and the newer agents,
referred to as novel or atypical. Positive symptoms respond well to both typical and atypical
antipsychotics, but negative symptoms respond better to atypicals. The typical antipsychotics
are divided into high-potency (or low-dosage) and low-potency (or high-dosage). Among the
typicals, haloperidol and pimozide are the drugs of choice for treating children with Tourette's
disorder. Clozapine, an atypical agent, is particularly useful in treating refractory
schizophrenia in adolescence. The atypical agent risperidone is useful in treating some
symptoms associated with pervasive developmental disorders.
Several different types of antidepressants are used for treating children and adolescents with
psychiatric disorders. Tricyclic antidepressants (e.g., imipramine, amitriptyline, desipramine,
nortriptyline) have been used extensively to treat nocturnal enuresis, obsessivecompulsive
disorder, ADHD, and anxiety disorders (e.g., school phobia, separation anxiety). Tricyclic
antidepressants are no longer considered first-line drugs because of the clinical concern over
their cardiovascular safety profile. A new generation of antidepressants, called selective
serotonin reuptake inhibitors (SSRIs, e.g., fluoxetine, paroxetine, sertraline, fluvoxamine, and
citalopram), with much safer side effect profiles has been introduced. They are clearly
effective for the treatment of depressive and obsessive-compulsive disorders and are probably
effective for selective mutism, school phobia, and separation anxiety. Other antidepressants,
such as venlafaxine, nefazodone, trazodone, mirtazapine, and bupropion, are beginning to be
used with children and adolescents. Their effectiveness with specific disorders has yet to be

established, with the exception of bupropion, which has proven efficacy in the treatment of
ADHD.
Lithium carbonate is the main antimanic drug used with children, with the anticonvulsants
carbamazepine and valproic acid used as alternative antimanic agents. Lithium carbonate is
currently indicated for the treatment of bipolar disorder, aggression, impulsivity, and temper
tantrums in children. The drug works reasonably well in children with behavior problems that
are characterized by impulsivity, aggressiveness, rage, or emotional lability. However,
clinicians are cautioned that most of this understanding comes from clinical experience and
not from double-blind, placebocontrolled studies. Carbamazepine and valproic acid are
indicated for bipolar disorder and as an adjunct treatment in refractory major depressive
disorders.
Antianxiety agents, also called anxiolytics, are used to treat the various anxiety disorders seen
in children (e.g., separation anxiety disorder, panic disorder, agoraphobia, school phobia, and
generalized anxiety disorder). Benzodiazepines are the most notable agents. They are also
known as sedative-hypnotics because they act as sedatives in low doses, as anxiolytics at
moderate doses, and as hypnotics in high doses. In general, sedatives reduce daytime activity,
temper excitement, and generally calm the child, and hypnotics produce drowsiness and
facilitate the onset and maintenance of sleep. High-potency benzodiazepines (e.g.,
clonazepam, alprazolam, lorazepam) are used in the treatment of anxiety disorders and as
adjuncts in the treatment of refractory psychosis and mania, severe agitation, Tourette's
disorder, severe insomnia, and major depressive disorder with anxiety. Buspirone, an atypical
anxiolytic, is also used for anxiety disorders and as an adjunct in the treatment of refractory
obsessive-compulsive disorder and for treating aggressive behaviors in children with mental
retardation and autism.
Stimulants are probably the most widely used psychotropic drugs with children. The most
commonly used stimulants include dextroamphetamine, methylphenidate, and magnesium
pemoline. They are indicated for ADHD, ADHD with comorbid disorders, ADHD in children
with developmental disabilities, and as adjunctive therapy for refractory depression.
Generally, stimulants are effective in controlling the symptoms of ADHD, especially
hyperactivity, impulsivity, distraction, and inattention. Furthermore, they are effective in
improving parent-child interactions, peer relationships, academic productivity, and classroom
behavior. Stimulants minimally affect academic achievement, but they do enhance
performance on measures of vigilance, impulse control, fine motor coordination, and reaction
time.

COMPLICATIONS
All medications used to treat psychiatric disorders generally have adverse effects. The issue is
whether, on balance, the benefits of using psychotropic drugs to treat the disorder outweigh
the adverse effects associated with them. Typically, the benefits outweigh the costs, but there
are definite risks involved in using drugs for treating childhood disorders. For example, most
drugs can cause weight gain, some by as much as 30% to 40% in less than a year, and
excessive weight gain is a risk factor for type 2 diabetes.
Certain adverse effects are associated with the different classes of drugs. For example, even
when effective, the typical antipsychotic medications may produce Parkinsonian signs (e.g.,
muscle stiffness, gait disturbance, and tremors), abnormal muscle contractions, drowsiness

and sedation, and anticholinergic side effects (e.g., dry mouth, constipation, urinary retention,
and blurred vision). Other side effects include other movement disorders as well as
cardiovascular and hematological adverse effects. The antimanic drug lithium has the
potential to induce central nervous system confusional state, gastrointestinal disturbance, and
kidney problems. The anxiolytic agents, such as benzodiazepines, have the short-term
problem of sedation that may interfere with learning and can cause drug dependency in the
longer term. Furthermore, anxiolytic agents may cause irritability and aggressiveness. The
most frequently reported adverse effects of stimulants include insomnia, decreased appetite,
weight loss, abdominal pain, and headaches.
When using medications for the adjunctive treatment of childhood disorders, clinicians
carefully monitor medical, physical, behavioral, and cognitive side effects. They use data on
the intended and adverse effects of medication to revise the child's treatment plan so that the
smallest effective dose can be prescribed.

CASE ILLUSTRATION
Monica was a 15-year-old who had been a wellbehaved young lady until about 4 months
ago, when she began displaying behavior problems. These included verbal outbursts,
irritability, changes in mood, grandiosity, and hyper-episodes (e.g., not sleeping for several
days, excessive shopping). Furthermore, both her parents and teachers reported increasing
oppositional behaviors at home and at school. A few weeks prior to seeing her family
physician, Monica began smoking and drinking alcohol, activities that she had abhorred
before. Her family physician noted that these were common problems of adolescence, and
with parental support and understanding, she would gradually grow out of it.
As Monica's behavior worsened, it reminded her father that his younger brother had exhibited
similar behaviors during his teen years that necessitated treatment with lithium before he got
better. Thus, he arranged a psychiatric consultation for Monica. The psychiatric assessment
suggested that Monica met some of the signs and symptoms of bipolar disorder and had a
paternal family history of bipolar disorder and maternal family history of depression and
alcohol abuse. Her parents maintained that until the last 4 or 5 months, Monica was a
completely different child. The psychiatrist suggested a provisional diagnosis of bipolar
disorder and prescribed her a daily dose of lithium that was maintained at steady-state serum
levels between 0.9 and 1.1 mEq/L.
Most of Monica's signs and symptoms were resolved within 6 to 8 weeks of pharmacotherapy.
She was referred for cognitive-behavioral therapy with the following goals: increasing her
knowledge of bipolar disorder and its treatment, teaching her cognitive behavioral skills for
coping with psychosocial stressors and related problems, facilitating compliance with
pharmacological and cognitive behavioral interventions, self-monitoring the occurrence and
severity of her symptoms, and seeking professional help when necessary. Monica is back on
track with her life and knows what to do about her disorder.
Nirbhay N. Singh and Mohamed Sabaawi
Further Reading

Entry Citation:
Singh, Nirbhay N., and Mohamed Sabaawi. "Pharmacotherapy." Encyclopedia of Behavior
Modification and Cognitive Behavior Therapy. 2007. SAGE Publications. 15 Apr. 2008.
<http://sage-ereference.com/cbt/Article_n2090.html>.