Antipsychotic agents extrapyramidal symptoms

Antipsychotic agents acetylcholinesterase inhibitors may increase the risk of antipsychotic-related extrapyramidal symptoms. 

Delusions/Psychosis. Demented patients who are acutely psychotic and agitated should be treated in much the same manner as demented patients with delirium. Low doses of a high potency conventional antipsychotic like haloperidol were once preferred. This was mainly because it can be given both orally and by injection. In recent years, the atypical antipsychotic ziprasidone, which is now also available in oral and injectable forms, has superseded haloperidol as the preferred agent when treating the acutely psychotic and agitated patient with dementia. As previously noted, ziprasidone affords the same tranquilizing benefit as haloperidol, it can now be administered via injection when necessary, and it avoids the problematic extrapyramidal symptoms of haloperidol to which patients with dementia are often keenly sensitive. 

Most antipsychotics and especially the piperazines and the butyrophenones can cause extrapyra-midal symptoms. Blockade of dopamine receptors mainly in the corpus striatum is held responsible for these extrapyramidal effects. They may become manifest as a variety of clinical symptoms and it should be noted that within 24 8 hours after the beginning of treatment acute dystonic reactions like torticollis, facial grimacing and opisthotonos may occur. Parkinsonism-like symptoms such as bradyki-nesia, rigidity and tremor occur after weeks or months of therapy and are more common in the elderly. Motor restlessness, i.e. akathisia, also mostly occurs not before weeks or months after starting therapy. The tendency of an antipsychotic agent to produce extrapyramidal symptoms appears to be inversely related to its ability to block cholinergic receptors. 

FIGURE 11 — 11. One compensation for the overactivity of acetylcholine that occurs when dopamine receptors are blocked is to block the acetylcholine receptors with an anticholinergic agent. Thus, anticholinergics overcome excess acetylcholine activity caused by removal of dopamine inhibition when dopamine receptors are blocked by conventional antipsychotics. This also means that extrapyramidal symptoms (EPS) are reduced. 

Lemmens P, Brecher M, Van Baelen B. A combined analysis of double-blind studies with risperidone vs. placebo and other antipsychotic agents factors associated with extrapyramidal symptoms. Acta Psychiatr Scand 1999 99(3) 160-70. 

Attenuation of brain dopamine (DA) neurotransmission has been widely recognized as a useful mechanism for the treatment of the psychotic symptoms of schizophrenia.1-3 Antagonism of DA receptors is a major component of the mechanism of action of classical antipsychotic agents such as haloperidol and chlorpromazine as well as the newer atypical agents such as clozapine,4,5 risperidone,6 sertindole,7 and olanzapine.8 9 However a significant portion of schizophrenic patients do not respond to DA antagonist therapy and their use is often limited by a variety of severe side effects including extrapyramidal side effects (EPS) and tardive dyskinesia (TD).10-12 While atypical antipsy-... 

The belladonna alkaloids and related muscarinic receptor antagonists have long been used in parkinsonism. These agents can be effective adjuncts to treatment with levodopa see Chapter 20). Muscarinic receptor antagonists also are used to treat the extrapyramidal symptoms that commonly occur as side effects of conventional antipsychotic drug therapy see Chapter 18). Certain antipsychotic drugs are relatively potent muscarinic receptor antagonists, and these cause fewer extrapyramidal side effects. 

RISPERDAL), for example, is a potent S-HT and receptor antagonist. Low doses of risperidone have been reported to attenuate negative symptoms of schizophrenia with a low incidence of extrapyramidal side effects. Extrapyramidal effects are commonly seen, however, with doses of risperidone in excess of 6 mg/day. Other atypical antipsychotic agents—quetiapine (seroquel) and olanzapine (zyprexa)—act on multiple receptors, but their antipsychotic properties are thought to be due to antagonism of DA and 5-HT. 

It is a dibenzodiazepine derivative. It is an unusual antipsychotic agent which hardly produces any extrapyramidal symptoms. It possesses the ability to suppress symptoms of tardive dyskinesia. 

---