Atypical neuroleptics/antipsychotics olanzapine, risperidone

Atypical antipsychotics The second generation or so-called atypical antipsychotics have chemical, pharmacological, and clinical properties that are different from those of the classical antipsychotics/ neuroleptics. The most commonly used atypicals include clozapine, olanzapine, risperidone, and quetiapine. 

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

The main indications for atypical antipsychotics are the acute and maintenance treatment of schizophrenic disorders, with an emphasis on the treatment of refractory and chronic disorders. However, because of the lower risk of EPS and in particular of tardive dyskinesia, there is a tendency toward a wider range of indications for some of the atypical neuroleptics. Favorable effects in drug-induced psychoses have been demonstrated for olanzapine. Clozapine seems effective in the treatment and relapse prevention of manic episodes and bipolar disorders, and risperidone has been shown to have good efficacy in conduct disorders and in the pervasive developmental disorders. 

The results of a similar study of ours, in which the study drugs were three atypical neuroleptics or antipsychotics, are given in Table 5-4. During the time of this study, clozapine, olanzapine, and risperidone were the only atypical neuroleptic or antipsychotic agents in general use at HCPC these three drugs were selectively used in accordance with the clinical criteria set by the Harris County Mental Health and Mental Retardation Authority. These criteria included documentation of at least two failures to respond clinically to treatment with different typical neuroleptic agents. 

Findings of our study of atypical neuroleptics and antipsychot-ics show that African American patients may need a higher dose of clozapine than that required by Caucasian patients. Likewise, it appears that African Americans may need a higher dose of olanzapine than Caucasians do and that Hispanics have intermediate requirements. Asian patients appear to require the lowest dose of all, but it must be noted that the study included a relatively small sample of Asians. Finally, Hispanics may need a lower dose of risperidone than that required by African Americans or Caucasians, and the dose difference between the latter two groups may be negligible. 

As noted earlier, evidence indicates that atypical antipsychotics may also produce NMS ( 488). Several patients have developed NMS after treatment with clozapine, risperidone, or olanzapine. A few of these cases are classic NMS, with symptoms such as markedly elevated temperature and CPK levels. For each drug, approximately a dozen reported cases fulfill a reasonably stringent criteria for NMS, whereas the rest can be considered borderline. The number of NMS cases, however, appears low relative to use. In addition, some of the patients on clozapine who developed NMS were also receiving neuroleptics. There are cases of patients who had NMS on clozapine alone, however, and when rechallenged with clozapine experienced another NMS episode. Similarly, rechallenge with olanzapine- or risperidone-induced NMS has resulted in either questionable or definite reemergence of NMS. 

The term neuroleptic is often applied to drngs that have relatively prominent experimental and clinical evidence of antagonism of D2-dopamine-receptor activity, with substantial risk of adverse extrapyramidal nenrological effects and inaeased release of prolactin. The term atypical antipsychotic is applied to agents that are associated with snbstantially lower risks of snch extrapyramidal effects. Representative examples inclnde aripiprazole, clozapine, quetiapine, ziprasidone, and low doses of olanzapine and risperidone. 

Although the term neuroleptic initially encompassed this whole unique syndrome and is still used as a synonym for antipsychotic, it now is used to emphasize the more neurological aspects of the syndrome i.e., the parkinsonian and other extrapyramidal effects). Except for clozapine, arip-iprazole, quetiapine, ziprasidone, and low doses of olanzapine and risperidone, antipsychotic drugs available in the U.S. also have effects on movement and posture and can be called neuroleptic. The more general term antipsychotic is preferable, as reinforced by the growing number of modern atypical antipsychotic drugs with little extrapyramidal action. 

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