Pediatric Movement Disorders - Treatments

Neuroleptics

Neuroleptics are a class of medications that were originally developed to treat psychosis. Neuroleptics work by blocking dopamine D2-like receptors. This action is thought to have a potentiating effect on the indirect pathway of basal ganglia transmission, thereby inhibiting excess activity in the cortex. Different neuroleptics have different effects on subclasses of the D2-like receptors. This probably accounts for their slightly different actions and side effects.

Because neuroleptics stimulate the relatively inhibitory indirect pathway, these drugs are also used to treat disorders of excess involuntary movement. In particular, neuroleptics are very helpful for tic disorders, and occasionally helpful in chorea. They can also be used to treat nausea, psychosis, hallucinations, or behavioral changes caused by L-dopa or dopamine agonists.

Pimozide (Orap®) and haloperidol (Haldol®) are two of the most commonly used neuroleptics for tics in children. Other commonly used neuroleptics include thioridazine (Mellaril®) and fluphenazine (Prolixin®). Newer, "atypical" neuroleptics may have a decreased rate of neurological side effects, including clozapine (Clozaril®), risperidone (Risperdal®), quetiapine (Seroquel®), and olanzapine (Zyprexa®).

The side effects of neuroleptics can be very serious and they do not always resolve following discontinuation of the medication. In particular, all neuroleptics, with the exception (thus far) of clozapine have been reported to induce parkinsonism and tardive symptoms, including tardive dyskinesia and tardive dystonia. "Tardive" refers to the late occurrence of symptoms, often many months after starting the medicine, and, in some cases, many months after stopping the medicine.

Tardive dyskinesia, a "rabbit-like" movement of the mouth and lower face, and tardive dystonia are difficult to treat and often do not resolve once started. Neuroleptics may also cause an acute dystonic reaction, which occurs when starting the medication for the first time or increasing the dose. In an acute dystonic reaction, the neck or the back arches involuntarily, and the mouth, tongue, and face may be pulled to one side or have continuous rolling or writhing movements. Acute dystonic reactions are usually treated with an intravenous injection of diphenhydramine (Benadryl®). Neuroleptic malignant syndrome, characterized by confusion, stiffening of the muscles, high temperature, and elevated muscle enzymes in the blood, is a rare, potentially life-threatening complication of neuroleptic treatment. This syndrome is more likely to occur if neuroleptics are suddenly discontinued. (Neuroleptic malignant syndrome has also been reported after rapid withdrawal from dopamine.) Therefore, it is important to taper the dose gradually before stopping any neuroleptic. Although clozapine may have fewer neurological side effects than other neuroleptics, it may cause a life-threatening decrease in the white blood cell count. During treatment with clozapine, blood needs to be tested frequently (usually every week) and closely monitored.