Risks Associated With Atypical Antipsychotic Drugs

RISKS ASSOCIATED WITH ATYPICAL ANTIPSYCHOTIC DRUGS 

As previously noted in chapter 2, the NIMH CATIE study summed up, There were no statistically significant differences between the rates of 

Although relatively little has thus far been written about it, the newer neuroleptics can also cause akinesia, depression, psychosis, and suicidality. Aripiprazole (Abilify) has already been reported to cause or worsen psychosis (Grover et al., 2006 Raja, 2007). I have seen several cases in which olanzapine (Zyprexa) has caused zombielike behavior and profound depression. As chapter 2 also documented, all of the newer neuroleptics, including Risperdal, Geodon, and Seroquel, suppress dopaminergic function (dopamine D2), the most probable neurochemical cause of these clinical states (Wu et al., 2007). 

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RISKS ASSOCIATED WITH ATYPICAL ANTIPSYCHOTIC DRUGS... 

Imfeld et al. [55] observed that the incidence rates of ischemic stroke for patients with AD, VD, or no dementia were 4.7/1,000 person-years (PYs), 12.8/1,000 PYs, and 5.1/1,000 PYs, respectively. Compared with dementia-free patients, the odds ratio of developing a transitory ischemic attack (TIA) for patients with AD treated with atypical antipsychotic drugs was 4.5. According to these results, patients with VD, but not AD, have a higher risk of developing an ischemic stroke than those without dementia. In patients with AD, but not VD, use of atypical antipsychotic drugs was associated with an increased risk of TIA. 

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... 

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. 

Clozapine, the first of the class of atypical antipsychotic drugs, rarely causes EPS, and it is the only antipsychotic drug that is not associated with treatment-emergent tardive dyskinesia. Because of the approximately 1% risk of potentially fatal agranulocytosis, the use of clozapine is restricted to patients who have not responded to or cannot tolerate other antipsychotic drugs. 

Hyperlipidemia associated with antipsychotic drugs has been reviewed (SEDA-29, 64). Haloperidol and the atypical antipsychotic drugs ziprasidone, risperidone, and aripiprazole would be associated with lower risks of hyperlipidemia, whereas chlorpromazine, thioridazine, and the atypical drugs quetiapine, olanzapine, and clozapine would be associated with higher risks. However, severe clozapine-induced hypercholesterolemia and hypertriglyceridemia has been reported in a patient taking clozapine (55). 

Prochlorperazine is a potent phenothiazine antipsychotic drug that is associated with a high risk of extrapyramidal side-effects, a low degree of sedation and of antimuscarinic side-effects. Chlorpromazine is less likely to induce extrapyramidal side-effects but has increased risks of inducing sedation and antimuscarinic side-effects. Olanzapine is classified as an atypical antipsychotic having characteristically much fewer incidences of extrapyramidal... 

Most conventional antipsychotics are associated with a dose-depen-dent risk of a lowered seizure threshold, although the incidence of seizures with most of these drugs is quite small (Devinsky et al. 1991). Of all the conventional antipsychotics, molindone and fluphenazine have been shown most consistently to have the lowest potential for this side effect (ltd and Soldatos 1980 Ohver et al. 1982). The atypical antipsychotic clozapine is associated with a dose-dependent risk of seizure. 

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

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