31.18d Pharmacotherapy
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given once per day and increased to a therapeutic dose ranging
between 1.4 mg/kg and 1.8 mg/kg, either in one dose or in two
divided doses.
Second generation Antipsychotics
(SGAS) and Conventional
Antipsychotic Agents
The SGAs represent a major advance in the pharmacologi-
cal treatment of schizophrenia in children and adolescents, as
well as in adults. The atypical antipsychotic agents have largely
replaced traditional antipsychotics because of their more favor-
able side-effect profiles, greater effectiveness for negative symp-
tomatology, and mood-stabilizing effects. Although the SGAs
are generally recommended currently as first-line agents in the
treatment of psychotic disorders in children and adolescents,
only one controlled NIMH trial has been conducted using an
atypical agent in the treatment of schizophrenia for youth.
This study examined clozapine and found it to be superior to
haloperidol for treating positive and negative symptoms of
schizophrenia in 21 youth. The serious drawbacks of clozapine,
however, limit it as a first-line agent for this disorder. In the
NIMH trial, five participants developed significant neutropenia,
and two experienced seizures. Clozapine is generally used only
for treatment-resistant schizophrenia.
Open label trials in youth with schizophrenia have suggested
efficacy of other atypical antipsychotic agents such as olanzap-
ine, risperidone, and quetiapine. Case reports have suggested
that ziprasidone is effective. One of the main side effects of the
atypical antipsychotic agents is significant weight gain. A newer
atypical agent, aripiprazole awaits clinical trials to confirm its
potential to be an efficacious and more weight neutral agent for
the treatment of childhood psychoses. Although conventional
antipsychotics, such as haloperidol, loxapine (Loxitane), and
thioridazine (Mellaril) have been shown to be significantly
superior to placebo in the treatment of psychosis in youth, given
their side effect profiles they are typically chosen as first-line
treatments. Schizophrenia with onset in late adolescence is
treated, as is adult-onset schizophrenia.
Aggressive, explosive, and assaultive behaviors associated
with disruptive behavior disorders, psychotic disorders, and
posttraumatic stress disorders have been treated with antipsy-
chotic agents with varying reports of success. Randomized
controlled trials with several atypical antipsychotics, such as
risperidone, olanzapine, quetiapine (Seroquel), and aripiprazole
(Abilify), have provided evidence of effectiveness for behav-
ioral improvement, with fewer long-term adverse effects than
typical antipsychotics.
When conduct disorder is associated with ADHD, a trial of a
stimulant is indicated; stimulants are faster acting than atypical
antipsychotics or mood-stabilizing agents used in clinical prac-
tice to control dangerously aggressive behaviors.
The management of severe aggression, disruptive behavior,
and ADHD remains a challenge. Combinations of antipsychot-
ics with mood-stabilizing agents or stimulants are sometimes
used in treatment-resistant cases, although few studies attest
to the efficacy or safety of drug combinations. Newer “atypi-
cal” antipsychotic medications—SDAs—such as risperidone,
olanzapine, clozapine (Clozaril), ziprasidone (Geodon), and
aripiprazole have enabled a wider range of treatment-resistant
patients to benefit from neuroleptic treatment. The SDAs are
believed to relieve both the positive and negative symptoms
of schizophrenia and to produce less risk of extrapyramidal
adverse effects and less potential for the development of tar-
dive dyskinesia. Nevertheless, all antipsychotics pose some risk
of extrapyramidal adverse effects and tardive dyskinesia. One
challenge in obtaining optimal pharmacological treatment for
children is to decrease maladaptive behaviors while promoting
productive academic functioning. To this end, clinicians must
consider adverse effects of medication that result in cognitive
“dulling.” Certain pharmacological agents used in pediatric
populations are associated with a specific disorder or with target
symptoms that appear in several disorders. For example, halo-
peridol was shown in past studies to be effective in the treat-
ment of Tourette’s disorder, but it has also been used to control
severe aggression. The high-potency antipsychotics haloperidol
and pimozide (Orap) still have the greatest body of evidence as
effective medications for Tourette’s disorder, although they also
have considerable drawbacks. Pimozide prolongs the QT inter-
val and, thus, requires electrocardiography (ECG) monitoring.
Clonidine, a presynaptic
a
-adrenergic blocking agent, is less
effective than either of the above-mentioned antipsychotics, but
has the advantage of avoiding the risk for tardive dyskinesia;
sedation is a frequent side effect of clonidine.
Tic disorders often coexist with ADHD in children and ado-
lescents. Stimulant use is controversial; it can precipitate tics
and should be avoided in these patients, although recent stud-
ies indicate that the prohibition may not be totally warranted.
Clonidine sometimes reduces tics in both ADHD and the
comorbid cases.
Selective Serotonin Reuptake
Inhibitor (SSRI) Antidepressants and
Other Antidepressants
SSRI antidepressants have been found in randomized clinical
trials to have efficacy in the treatment of childhood anxiety dis-
orders, depressive disorders, and OCD. A substantial evidence
base exists for the efficacy of SSRIs in the treatment of sepa-
ration anxiety, generalized anxiety disorder, and social phobia
in children and adolescents. Thus, SSRIs are currently recom-
mended as first-line medications in the treatment of childhood
anxiety. Separation anxiety disorder, generalized anxiety disor-
der, and social phobia are often studied together because they
so commonly coexist. A given child with one of the preceding
anxiety disorders has a 60 percent chance of having a second
one, and in 30 percent of cases, all three are comorbid. Alpra-
zolam (Xanax) may be helpful in separation anxiety disorder,
but randomized clinical trials are still needed.
The SSRIs currently are the drugs of choice in the phar-
macological treatment of depressive disorders in children and
adolescents. Given the FDA placement of the “black-box”
warning on all antidepressants used in children and adolescents
because of the slightly increased risk of suicidal behaviors,
close monitoring of suicidal ideation and behavior is impera-
tive. Although most side effects of SSRIs are tolerable, anec-
dotal recent reports indicate occasional SSRI-induced apathy
