Antipsychotic agents/drugs atypical

Although atypical antipsychotic agents may cost several times as much as traditional antipsychotics, drug costs in schizophrenia account for only 1-4% of the total treatment cost (Knapp, 1997). The argument then is that a small increase in drug costs— say to 10% of total cost—may result in disproportionate savings in the highly expensive direct hospital costs, if clinical trial... 

Murray, M. (2006). Role of CYP pharmacogenetics and drug-drug interactions in the efficacy and safety of atypical and other antipsychotic agents. /. Pharm. Pharmacol, 58, 871— 85. 

Table 5-27 and Table 5-28 summarize the clinically relevant pharmacokinetic and pharmacodynamic properties of other novel antipsychotics ( 326). Drug interactions with these agents were not systematically evaluated because controlled clinical trials usually prohibit concurrent medications. There are also many special circumstances (e.g., patients with comorbid medical diseases, substance abuse, epilepsy, or atypical indications such as agitation associated with mental retardation or dementia) that are not usually addressed in clinical research trials. Thus, much remains to be learned about significant drug interactions in these patient groups. To our knowledge, however, no consistent, serious, clinically relevant interactions have been reported. 

Antipsychotic drugs are also indicated for schizoaffective disorders, which share characteristics of both schizophrenia and affective disorders. No fundamental difference between these two diagnoses has been reliably demonstrated. They are part of a continuum with bipolar psychotic disorder. The psychotic aspects of the illness require treatment with antipsychotic drugs, which may be used with other drugs such as antidepressants, lithium, or valproic acid. The manic phase in bipolar affective disorder often requires treatment with antipsychotic agents, although lithium or valproic acid supplemented with high-potency benzodiazepines (eg, lorazepam or clonazepam) may suffice in milder cases. Recent controlled trials support the efficacy of monotherapy with atypical antipsychotics in the acute phase (up to 4 weeks) of mania, and olanzapine and quetiapine has been approved for this indication. 

As mania subsides, the antipsychotic drug may be withdrawn, although maintenance treatment with atypical antipsychotic agents has become more common. Nonmanic excited states may also be managed by antipsychotics, often in combination with benzodiazepines. 

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. 

Antipsychotic drugs include the older phenothiazines and butyrophenones, as well as newer atypical drugs. All of these can cause CNS depression, seizures, and hypotension. Some can cause QT prolongation. The potent dopamine D2 blockers are also associated with parkinsonian-like movement disorders (dystonic reactions) and in rare cases with the neuroleptic malignant syndrome, characterized by "lead-pipe" rigidity, hyperthermia, and autonomic instability (see Chapter 29 Antipsychotic Agents Lithium). 

Newer antipsychotic agents may also be helpful with regard to these concerns. The atypical antipsychotic clozapine was the first of the atypical antipsychotics, which offer significant advantages over typical antipsychotics (Kane et al. 1988). Clozapine is effective in many patients unresponsive to treatment with typical antipsychotics. It also seems to be associated with few extrapyra-midal symptoms (EPS) and a lower risk for TD. However, other features of the drug limit its use by African Americans. 

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. 

Classical antipsychotic agents induce EPS on chronic administration and also do not treat up to 30% of psychotic patients. Clozapine, a tricyclic benzodiazepine derivative, was the first antipsychotic drug to display a dramatically different pharmacological profile and did so both in animals and clinically. This profile created the concept of a new class of "atypical" antipsychotic drugs. 

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