Clinical Uses

The treatment of schizophrenia is the primary indication for the use of these drugs. The principal goals for the management of a chronic schizophrenic disorder are the minimizing of symptoms and the prevention of exacerbations. Antipsychotic effectiveness is demonstrated by their ability to reduce the rate of relapse in the chronic condition by about two-thirds to three-quarters compared to no treatment. Drug choice is determined mainly by the patient's past responses and the drug's potential for producing adverse effects. The clinical trend is to prescribe the higher-potency atypical agents.

All antipsychotics except clozapine have a similar potential for producing tardive dyskinesia, the most serious adverse effect. Clozapine is reserved for patients who have failed to respond to therapy with at least two other antipsychotics and for those who have disabling tardive dyskinesia. Therapy with clozapine has been reported to salvage up to half of otherwise treatment-refractory pa-

tients. Its second-line status follows from its ability to cause seizures and a fatal agranulocytosis in large doses.

Substantial therapeutic margins exist for doses of antipsychotic drugs. Once the disorder is controlled, single daily doses are preferred. Bedtime dosing facilitates compliance and takes advantage of the sedation produced by some agents, and patients have fewer adverse reactions. Use of large doses, or rapidly increasing doses to treat severe conditions, has not proved beneficial because of the incidence of acute dystonic reactions. A parenteral form of haloperidol offers the advantage of greater bioavailability and so can be used for rapid initiation or for long-term maintenance in noncompliant individuals. During maintenance therapy, continual dosing with the smallest possible antipsychotic dose is preferred, as opposed to "as needed" treatment for recurrent episodes. Therapy is typically continued for at least a year after remissions are apparent.

Schizoaffective disorders have depression or mania as a major component in addition to psychosis. Thus, lithium or an antidepressant may have to be added to the regimen. Antipsychotic agents are also used in the initial therapy of mania because the patient's response is more rapid than with lithium. As the condition subsides, the antipsychotic can be withdrawn.

Tourette's syndrome, a heterogeneous behavioral disorder associated with motor and vocal tics of variable form and severity, can be effectively treated with haloperidol. Antipsychotics can also be employed to control disturbed behavior in senile dementia or Alzheimer's disease, since they decrease confusion, agitation, and hyperactivity. Most of these drugs also exhibit a strong antiemetic effect and can sometimes be used clinically for this purpose.

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