THE ANTIPSYCHOTICS : A Pediatric Perspective - 08/09/11
Résumé |
Antipsychotics are medications that reduce the symptoms of hallucinations and delusions that characterize psychosis. They have been used in the treatment of patients with schizophrenia for more than 45 years.48 Fourteen antipsychotics are currently marketed in the United States. Ten are considered “typical” antipsychotics. The “typical” antipsychotics are all equally effective in their ability to reduce symptoms of psychosis. Because adolescents with a psychotic illness are often treated with doses of antipsychotics similar to those used in adults, a listing of these medications and their dosing in adults with psychotic disorders is shown in Table 1.
More recently, four agents considered “atypical” antipsychotics became available. What distinguishes the typical from the atypical antipsychotics is that atypical antipsychotics are associated with a reduced or absent risk for extrapyramidal side effects (EPSs).119 A list of these medications and their usual daily dosing for adults with schizophrenia are shown in Table 2. Other than the 14 agents that are marketed for use in psychotic disorders, two other medications with antipsychotic properties are currently marketed for neuropsychiatric illnesses in the United States. Pimozide (Orap) is labeled for use for treatment-resistant Tourette syndrome, whereas amoxapine (Asendin) is marketed as an antidepressant.
As can be seen from Table 1 and Table 2, daily doses of antipsychotics (in mg) generally used to treat schizophrenia in adults vary widely between compounds. Medications that are generally administered in larger daily doses (in mg) are considered “low-potency” agents (e.g., chlorpromazine, thioridazine, and clozapine). Similarly, medications that are generally given in smaller daily doses (in mg) are considerd “high-potency” agents (e.g., haloperidol, fluphenazine, and risperidone). As is discussed later, the distinction between high- and low-potency compounds is important when considering side effects. But “potency” does not reflect an agent's ability to reduce target symptoms of psychosis.
Other than their ability to treat psychotic illnesses, what the antipsychotic medications also have in common is that they all reversibly block type 2 dopamine (D2) receptors in the central nervous system. As can be seen in Table 1 and Table 2, the usual daily dosing for antipsychotics in adults with psychotic disorders is generally related to each medication's ability to block D2 receptors. Specifically, drugs with greater affinity for D2 receptors are generally more potent than those with lower D2 receptor affinity.53, 141, 151, 152 This finding led to the view that D2 receptor blockade was pivotal for the treatment of psychosis.119
At therapeutic doses, all antipsychotics bind to other receptors in the central nervous system to varying degrees. These include muscarinic, ⍺-adrenergic (both ⍺1 and ⍺2), histaminergic (H1) receptors, and several serotonin receptors. As is discussed later, an antipsychotic's blockade of these other receptors causes some of the side effects seen with each agent at therapeutic doses.26, 152
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| Address reprint requests to Robert L. Findling, MD, Department of Psychiatry, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106 The investigators' research is funded in part by Janssen Research Foundation, Eli Lilly & Company, Zeneca Pharmaceuticals, Abbott Laboratories, and Pfizer, Inc. This work was funded, in part, by the Stanley Foundation, NICHD grant HD31323-04 (Pediatric Pharmacology Research Unit), and the Children's Research Foundation of Cleveland. |
Vol 45 - N° 5
P. 1205-1232 - octobre 1998 Retour au numéro
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