Kids on Meds by Kevin T. Kalikow

Author:Kevin T. Kalikow
Language: eng
Format: epub
Publisher: W. W. Norton & Company

The First-and Second-Generation Antipsychotics

Let's take a more detailed look at individual antipsychotic medications.

Specific Second-Generation Antipsychotics

There are currently about a half dozen SGAs, including clozapine, risperidone, olanzapine, quetiapine, aripiprazole, and ziprasidone, the last two really being members of the third generation of antipsychotics.

Clozapine

Clozapine was the first marketed SGA. It works by blocking dopamine at a number of different dopamine and serotonin receptors. It binds D2 relatively weakly and is strongly anticholinergic. It is not FDA approved for use in children and adolescents.

When clozapine was introduced in the late 1980s as the first SGA, its ability to improve the negative symptoms of schizophrenia gave hope that the SGAs would be a major improvement over the FGAs, which had been used for the previous 30 years. And in fact, clozapine has proven uniquely effective in adult schizophrenia.

A few early studies in children with schizophrenia showed it to be superior to haloperidol (Kumra, 1996), an FGA, and very effective in children with schizophrenia who did not respond to other medication. In particular, one study showed it to be more effective than olanzapine in improving the negative symptoms of childhood schizophrenia (Rapoport, Gogtay and Shaw, 2008).

The unique efficacy of clozapine, however, must be measured against its significant side effects. These have led to its diminished use in both adults and children. The most important of these is agranulocytosis (see above). This requires that white blood cell (WBC) levels in the blood be monitored on a regular basis.

In addition, clozapine can lower the seizure threshold, making seizures more likely. This is particularly worrisome in children with PDDs, who are already more prone to seizures. Because clozapine is strongly anticholinergic, side effects such as dry mouth and orthostatic blood pressure changes must be monitored. Clozapine is also one of the SGAs most strongly associated with weight gain. Therefore the patient must be followed for changes in weight and blood levels of cholesterol, lipids, and sugar. Clozapine is also relatively sedating.

Clozapine is metabolized by a few different enzymes. Of particular importance are its potential interactions with fluvoxamine, fluoxetine, and paroxetine, all of which inhibit some of the enzymes that metabolize clozapine. These therefore have the potential to increase clozapine levels, although individuals might vary greatly. Other substances that increase the level of various enzymes, such as cigarettes and some antiseizure medicines, can decrease clozapine levels. If, however, these substances are stopped, enzyme levels drop, and clozapine levels might increase.

Overall, the use of clozapine is hampered by its side effects. It nevertheless remains a treatment of choice for children with schizophrenia who have not responded to other treatments.

Risperidone

Risperidone is FDA approved for use in adults with schizophrenia and with mania. It was also the first SGA to gain FDA approval in children, being approved for the extreme irritability and agitation of children with autistic disorder. Subsequently it was approved for the treatment of adolescents with schizophrenia and 10-to 17-year-olds with bipolar disorder mania or mixed states. Risperidone has also been shown to be as effective as pimozide and clonidine in treating the tics of Tourette's disorder.

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