Kaplan + Sadock's Synopsis of Psychiatry, 11e

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31.18d Pharmacotherapy

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. 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 Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants and Other Antidepressants

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