Atypical antipsychotics. See

Robertson, GS, Mastumura, H and Fibiger, HC (1994) Induction patterns of Ebi -like immuno-reactivity in the forebrain as predictors of atypical antipsychotic activity. J. Pharmacol. Exp. Ther. 271 1058-1061 (see also Neuropsychopharmacology 14 105-110). 

Introduced in clinical practice in the 1960s, lithium was the first mood stabilizer to be used in China. This was followed by carbamazepine and sodium valproate. For many years, these were the only treatment options available as mood stabilizers. Although lamotrigine was approved for maintenance treatment of bipolar I disorder in 2003 by FDA (Food and Drug Administration) in the USA, this indication has not yet been approved by the Chinese authorities. At present, only one atypical antipsychotic drug, risperidone, has been approved for treating acute mania (February 2005 by SFDA [State Food and Drug Administration]) in China (see Table 6.1). 

The overall mean chlorpromazine-equivalents per day (CPZe) dose prescribed differed significantly, with lower dosing in Thailand compared with Malaysia and Australia (p < 0.001) (see Table 11.4). Pairwise comparisons revealed that the mean typical antipsychotic dose was significantly higher in Malaysia compared with Thailand (p < 0.001) and NWMH (p < 0.001). There were significant differences observed (p < 0.001) while comparisons of the mean atypical antipsychotic dose showed that Australia was significantly higher compared with Thailand (p < 0.001) and Malaysia (p < 0.001). 

The predominant mechanism by which currently available antipsychotic medications interfere with dopamine activity is by blockade of dopamine receptors on neurons innervated by dopamine nerve terminals. Of the five types of dopamine receptors, all antipsychotics share in common the fact that they block the dopamine type 2 receptor, also known as the D2 receptor, to a varying degree. Some of the atypical antipsychotics also block other dopamine receptors (see Table 13.5). The role of blockade of Dl, D3, D4, and other dopamine receptors in the therapentic effects of antipsychotic drugs remains unclear. Aripiprazole is an exception to this in that it is a partial agonist at the D2 receptor. 

The availability of the more recent, so-called atypical antipsychotics (clozapine, olanzapine, quetiapine, risperidone see Table 1.2) makes it prudent... 

FIGURE 11-23. Here postsynaptic dopamine 2 receptors are being blocked by a serotonin-dopamine antagonist (SDA) atypical antipsychotic in the nigrostriatal dopamine pathway. This shows what would happen if only the dopamine 2 blocking action of an atypical antipsychotic were active— namely, the drug would only bind to postsynaptic D2 receptors and block them. However, see Figure 11-24. 

Although it is not yet clear why the various atypical antipsychotics differ from each other, the answer is most likely to be found in the pharmacologic properties, other than serotonin 2A dopamine—2 antagonism, that they do not share in common. Although some of these properties are still unknown, many of them are known (and are shown in Figure 11—34 and in the individual icons for the various atypical antipsychotics discussed later in this chapter). Of the 17 pharmacologic properties detailed in these icons, some undoubtedly mediate side effects, and others may mediate additional therapeutic actions mentioned here. This raises the question Are atypical antipsychotics with multiple therapeutic mechanisms better than those with fewer therapeutic mechanisms (see Fig. 11-35) This theme of multiple pharma-... 

Although the usefulness of the atypical antipsychotics is best documented for the positive symptoms of schizophrenia, numerous studies are documenting the utility of these agents for the treatment of positive symptoms associated with several other disorders (discussed in Chapter 10 see Fig. 10—2). Atypical antipsychotics have become first-line acute and maintenance treatments for positive symptoms of psychosis, not only in schizophrenia but also in the acute manic and mixed manic-depressed phases of bipolar disorder in depressive psychosis and schizoaffective disorder in psychosis associated with behavioral disturbances in cognitive disorders such as Alzheimer s disease, Parkinson s disease, and other organic psychoses and in psychotic disorders in children and adolescents (Fig. 11—52, first-line treatments). In fact, current treatment standards have evolved in many countries so that atypical antipsychotics have largely replaced conventional antipsychotics for the treatment of positive psychotic symptoms except in a few specific clinical situations. 

Mood symptoms of depression are associated with many conditions in addition to major depressive disorder, including mood and anxiety symptoms in schizophrenia, schizoaffective disorder, bipolar manic/depressed/mixed/rapid cycling states, organic mood disorders, psychotic depression, childhood and adolescent mood disorders, treatment-resistant mood disorders, and many more (see Chapter 10, Fig. 10-6). Atypical antipsychotics are enjoying expanded use for the treatment of symptoms of depression and anxiety in schizophrenia that are troublesome but not severe enough to reach the diagnostic threshold for a major depressive episode or anxiety disorder in these cases the antipsychotics are used not only to reduce such symptoms but hopefully also to reduce suicide rates, which are so high in schizophrenia (Fig. 11 — 53). Atypical antipsychotics may also be useful adjunctive treatments to anti-... 

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