Antipsychotic drugs definition

For approximately 20% to 30% of people with schizophrenia, drug treatment is ineffective. A standard definition of treatment resistance includes patients who have persistent positive symptoms despite treatment with at least two different antipsychotics given at adequate doses (at least 600 chlorpro-mazine equivalents) for an adequate duration (4 to 6 weeks). In addition, patients must have a moderately severe illness as defined by rating instruments, and have a persistence of illness for at least 5 years.40 These patients are often highly symptomatic and require extensive periods of hospital care. 

In addition to the somatic side-effects of neuroleptics, there are a number of important psychiatric side-effects, such as demotivation or indifference (a direct effect of most drugs, actually part of the definition of the neuroleptic effect). This may mimic the negative features of the illness and may lead to prescriptions of an antidepressant when a reduction in dose or change of antipsychotic may be more appropriate. A second key problem is anxious activation or akathisia. This dose-dependent dysphoric state may lead to an apparent worsening in the clinical picture and accordingly an increase in antipsychotic dose rather than decrease and may be so intolerable as to lead on to suicide. 

Lithium, several (but not all) anticonvulsants, and most of the atypical antipsychotic medications are approved by the U.S. Food and Drug Administration (FDA) for the treatment of one of more phases of bipolar disorder. These medications are referred to as mood stabilizers, and they are the foundation of treatment for bipolar disorders. However, the skillful treatment of bipolar disorder requires not only the knowledge of how to prescribe one or more of these medications but also the understanding that some medications are preferred for one phase of the illness but not the other or for long-term use but not necessarily acute use. In this chapter, we first review the clinical use of lithium and the anticonvulsants that are definite or probable mood stabilizers. The general properties of atypical anti-psychotics are reviewed in Chapter 4. In this chapter, we expand on the use of these compounds for the treatment of bipolar disorder. Discussion of the treatment of each phase of bipolar disorder concludes the chapter. 

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 first generation antipsychotics, now known as typical drugs, were all D2 receptor blockers and, as such, very likely to produce Parkinsonian side effects. Because antipsychotic potency was associated with D2 receptor affinity, it was assumed that dopamine overactivity was the essential defect in schizophrenia and that a direct dopamine blockade was the definitive route to treatment. But these drugs affected both the target dopamine pathways of the mesolimbic projection and the uninvolved nigrostriatal projection. Unfortunately, that meant that movement disorders were the price that had to be paid for antipsychosis. 

Even before the identification of central 5-HTg receptors, 5-HTg receptor antagonists have been suggested to possess striking properties. To date, based on animal studies, several reports have shown that these drugs display anxiolytic, antipsychotic [see 3,4, 5,166,167], promnesic [72,169,170], antidepressant [136], antinociceptive [23, 171] and antiemetic [172, 173] properties, generally at low doses and without side-effects [4]. Confirmation of these results in human are necessary before drawing any definitive conclusion since, except for the antiemetic effects, data from clinical trials are few and generally limited to ondansetron. Critical reviews on the subject have recently been published [9, 235-238]. 

Further work on the butyrophenone CI-601 (9) confirmed earlier observations that the drug has definite antipsychotic properties, but that side effects were more troublesome than with existing therapeutic agents 27... 

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