Schizophrenia atypical antipsychotic drugs

The advent of novel atypical antipsychotic drugs has sharpened the debate in the UK about the cost burden of schizophrenia to the National Health Service (NHS) and the relative cost-effectiveness of these drugs. Schizophrenia has a prevalence of about 0.5% and a lifetime risk of 1%. Because the disease affects adolescents and has a lifetime course associated with a high degree of hospital and social... 

Revicki DA (1999). Pharmacoeconomic studies of atypical antipsychotic drugs for the treatment of schizophrenia. Schizophr Res33 (suppL), slOl-9. 

Figure 12.1 Cost of atypical antipsychotic drugs (clozapine and risperidone) in each country/territory for patients with schizophrenia...

Clozapine is the prototype of atypical antipsychotic drugs, and it has been used effectively to treat patients with schizophrenia who are unresponsive or intolerant to typical antipsychotics [7]. Clozapine is characterized as atypical by its preferential binding to serotonin (5-HT2) and dopamine D4 receptors (D4) relative to dopamine D2 receptors [8]. A recent body of work also suggests that atypicality may be defined by the rate at which clozapine dissociates from D2 receptors. Specifically, clo-... 

Current treatment of schizophrenia relies on atypical antipsychotic drugs 876... 

The same can be said for treating clients who have schizophrenia and other psychotic disorders. They must be stabilized in order to make progress in therapy. As mentioned in Chapter 2, antipsychotic drugs now allow marked improvement among clients with schizophrenia, and the newer, atypical antipsychotic drugs have fewer side effects so clients are more likely to comply with taking their... 

Another serious side effect of clozapine is a risk of seizures. This mainly occurs at higher doses of the drug, and having a seizure is not necessarily a sufficient reason to stop clozapine permanently. If the clozapine has been especially helpful, an anticonvulsant can be added to protect against further seizures. Valproate (Depakote) may be best in this regard because it not only provides protection from seizures but also may help to relieve some of the symptoms of schizophrenia. Recently, it has become clear that two atypical antipsychotic drugs, clozapine and olanzapine, are associated with an increased risk for the development of type II diabetes. 

Schizoid Personaiity Disorder (SPD). Again, there is very little research to guide in the selection of medications to treat the schizoid patient. If we conceptualize the symptoms of SPD as most resembling the negative symptoms of schizophrenia, the choice of agents would tend to favor the atypical antipsychotic drugs as opposed to the older typical antipsychotics. Consequently, we also recommend low doses of an atypical antipsychotic as a first-line treatment for SPD. 

Clozapine and olanzapine are atypical antipsychotic drugs used in the treatment of schizophrenia. Their strnctnres are depicted in Scheme 2.36. The use of clozapine and olanzapine, which are more effective than standard neuroleptic drugs in the treatment of refractory schizophrenia, is, however, limited becanse of their adverse effects. These adverse effects are ascribed to the formation of the corresponding cation-radicals in living organisms under oxidation by bone marrow cells. These cation-radicals eliminate protons from the NH fragments and generate their nitrenium cations. The nitreninm cations are covalently bonnd to the life-important proteins. This results in the toxic effects of clozapine and olanzapine (Sikora et al. 2007). 

Recently, a large study in the USA (CATIE) reported that perphenazine was as effective as atypical antipsychotic drugs, with the modest exception of olanzapine, and concluded that typical antipsychotic drugs are the treatment of choice for schizophrenia based on their lower cost. However, this study did not adequately consider the risk of tardivedyskinesia or the treatment history of patients in the design of this study. 

Nonpsychotic persons also experience impaired performance as judged by a number of psychomotor and psychometric tests. Psychotic individuals, however, may actually show improvement in their performance as the psychosis is alleviated. The ability of the atypical antipsychotic drugs to improve some domains of cognition in patients with schizophrenia and bipolar disorder is controversial. Some individuals experience marked improvement and for that reason, cognition should be assessed in all patients with schizophrenia and a trial of an atypical agent considered, even if positive symptoms are well controlled by typical agents. 

For approximately 70% of patients with schizophrenia, and probably for a similar proportion of patients with bipolar disorder with psychotic features, typical and atypical antipsychotic drugs are of equal efficacy for treating positive symptoms. However, the evidence favors atypical drugs for benefit for negative symptoms and cognition, for diminished risk of tardivedyskinesia and other forms of EPS, and for lesser increases in prolactin levels. 

This chapter will explore the various drug treatments for psychotic disorders, with special emphasis on schizophrenia. Such treatments include not only conventional antipsychotic drugs but also the newer atypical antipsychotic drugs, which are rapidly replacing the older conventional agents. We will also take a look into the future at the drugs under development for psychosis, especially schizophrenia. Mood stabilizers for bipolar disorders were covered in Chapter 7. 

This dilemma may have been solved in part by the atypical antipsychotic drugs described in the following section and is one of the reasons why the atypical antipsychotic agents are rapidly replacing the conventional ones in the treatment of schizophrenia and other psychotic disorders throughout the world. 

YamashitaH, Mori K, Nagao M, Okamoto Y, Morinobu S, Yamawaki S (2005) Influence of aging on the improvement of subjective sleep quality by atypical antipsychotic drugs in patients with schizophrenia comparison of middle-aged and older adults. Am J Geriatr Psychiatry 13 377-384... 

Atypical antipsychotic drugs (AADs), in addition to their application as a first-line treatment in schizophrenia, are also effective mood stabilizers. AADs are successfully used in unipolar and bipolar mood disorders, either as solo treatment or as adjuncts to SSRIs (Blier et al., 2005 Kennedy et al., 2001 Kennedy and Lam 2003 Papakostas et al., 2007 Simon and Nemeroff 2005 Tremblay and Blier 2006 Uzun et al., 2005). It has been suggested that the beneficial effect of AADs as adjuncts to SSRIs is explained, at least in part, by their ability to... 

The U.S. Food and Drug Administration today approved Risperdal (risperidone) for the treatment of schizophrenia in adolescents, ages 13 to 17, and for the short-term treatment of manic or mixed episodes of bipolar I disorder in children and adolescents ages 10 to 17. This is the first FDA approval of an atypical antipsychotic drug to treat either disorder in these age groups. 

Catatonic schizophrenia is a controversial syndrome, and there is debate about its etiology and treatment. There has been a report of two cases of catatonic schizophrenia successfully treated with clozapine a 49-year-old woman and a 19-year-old man (18). Both responded to clozapine despite being resistant to several conventional and atypical antipsychotic drugs and, in the second case, a course of electroconvulsive therapy. These two cases are intriguing, because the dose of clozapine required to improve catatonia was about double the dose required to improve psychosis significantly (600 mg/day and 750 mg/day). The two patients had common adverse effects of clozapine the first had mild nocturnal hypersalivation and mild/moderate constipation, and the second had moderate nocturnal hypersalivation. 

---