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.<sup>48 Delay J., Deniker P., Harl J.M. Utilisation en thérapeutique psychiatrique d’une phénothiazine d’action centrale élective (4560 RP) Ann Med Psychiatry 1952 ;  110 : 112-117

Haga clic aquí para ir a la sección de Referencias</sup> 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).<sup>119 Lieberman J.A. Atypical antipsychotic drugs as a first-line treatment of schizophrenia: A rationale and hypothesis J Clin Psychiatry 1996 ;  57 (suppl 57) : 68-71

Haga clic aquí para ir a la sección de Referencias</sup> 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.<sup>53 Feinberg A.P., Snyder S.H. Phenothiazine drugs: Structure–activity relationships explained by a conformation that mimics dopamine Proc Natl Acad Sci USA 1975 ;  72 : 1899-1903  [cross-ref]

Haga clic aquí para ir a la sección de Referencias, 141 Peroutka S.J., Snyder S.H. Relationship of neuroleptic drug effects at brain dopamine, serotonin, ⍺-adrenergic, and histamine receptors to clinical potency Am J Psychiatry 1980 ;  137 : 1518-1522

Haga clic aquí para ir a la sección de Referencias, 151 Richelson E. Neuroleptic affinities for human brain receptors and their use in predicting adverse effects J Clin Psychiatry 1984 ;  45 : 331-336

Haga clic aquí para ir a la sección de Referencias, 152 Richelson E. Preclinical pharmacology of neuroleptics: Focus on new generation compounds J Clin Psychiatry 1996 ;  57 (Suppl 11) : 4-11

Haga clic aquí para ir a la sección de Referencias</sup> This finding led to the view that D₂ receptor blockade was pivotal for the treatment of psychosis.<sup>119 Lieberman J.A. Atypical antipsychotic drugs as a first-line treatment of schizophrenia: A rationale and hypothesis J Clin Psychiatry 1996 ;  57 (suppl 57) : 68-71

Haga clic aquí para ir a la sección de Referencias</sup>

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.<sup>26 Bymaster F.P., Rasmussen K., Calligaro D.O. , y al. In vitro and in vivo biochemistry of olanzapine: A novel, atypical antipsychotic drug J Clin Psychiatry 1997 ;  58 (Suppl 10) : 28-36

Haga clic aquí para ir a la sección de Referencias, 152 Richelson E. Preclinical pharmacology of neuroleptics: Focus on new generation compounds J Clin Psychiatry 1996 ;  57 (Suppl 11) : 4-11

Haga clic aquí para ir a la sección de Referencias</sup>