Akathisia, antipsychotics causing

EPS include acute dystonic reactions, parkinsonian syndrome, akathisia, tardive dyskinesia, and neuroleptic mahgnant syndrome. Although high-potency conventional antipsychotics are more hkely than low-potency conventional antipsychotics to cause EPS, all first-generation antipsychotic drugs are equally hkely to cause tardive dyskinesia. The atypical antipsychotics cause suhstantially fewer EPS, which is one reason that they are recommended as first-line agents. 

Among the most significant adverse reactions associated with the antipsychotic dm are the extrapyramidal effects. The term extrapyramidal effects refers to a group of adverse reactions occurring on the extrapyramidal portion of the nervous system as a result of antipsychotic drains. This part of the nervous system affects body posture and promotes smooth and uninterrupted movement of various muscle groups. Antipsychotics disturb the function of the extrapyramidal portion of the nervous system, causing abnormal muscle movement. Extrapyramidal effects include Parkinson-like symptoms (see Chap. 29), akathisia, and dystonia (see Display 32-1). 

Treatment with AChs is disappointing, and reduction in antipsychotic dose may be the best intervention. Another alternative is to switch to an SGA, although akathisia occasionally occurs with the SGAs. Quetiapine and clozapine appear to have the lowest risk for causing akathisia. 

Infrequently, SSRIs produce dystonic reactions, which are intense mnscle spasms nsnally of the face and neck. They may cause akathisia, a restless inability to sit still. Dystonic reactions and akathisia are more commonly side effects of the dopamine-blocking antipsychotics. It is believed that SSRIs prodnce these effects because increasing 5HT activity tends to decrease dopamine. When these side effects occur, the SSRI should be switched to another antidepressant. 

Akathisia. Akathisia is yet another extrapyramidal side effect. The approach to treatment depends on its severity. For mild restlessness, dose reduction or dividing the daily dose to reduce the peak plasma levels of the medication may be successful. If mild akathisia remains a problem, it may be preferable to add a medication to treat this side effect or preferably switch to another antipsychotic or antidepressant that is less likely to cause akathisia. 

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. 

Most antipsychotic drugs cause unpleasant subjective effects in nonpsychotic individuals. The mild to severe EPS, including akathisia, sleepiness, restlessness, and autonomic effects are unlike any associated with more familiar sedatives or hypnotics. Nevertheless, low doses of some of these drugs, particularly quetiapine, are used to promote sleep onset and maintenance, although there is no approved indication for such usage. 

Amoxapine is a metabolite of the antipsychotic drug loxapine and retains some of its antipsychotic action and dopamine receptor antagonism. A combination of antidepressant and antipsychotic actions might make it a suitable drug for depression in psychotic patients. However, the dopamine antagonism may cause akathisia, parkinsonism, amenorrhea-galactorrhea syndrome, and perhaps tardive dyskinesia. 

The DSM-IV-TR observes that atypical antipsychotic drugs are less likely to cause akathisia than the new atypical drugs but that it does occur. In my experience, so-called atypicals like Risperdal and Zyprexa are equally likely to cause akathisia when given in doses equivalent to those used for the older drugs. 

Antidepressants are commonly used in combination with antipsychotics to treat depressive symptoms in individuals with schizophrenia. Different antidepressants have been reported to inhibit metabolism of different P450 pathways. Table 66-10 summarizes the potential metabolic drug interactions between antidepressants and SGAs. Potential enzyme inhibitor interactions with clozapine are the most clinically significant. Increased clozapine serum concentrations with a CYP 1A2 inhibitor such as fluvoxamine may precipitate seizures. With the newer atypical antipsychotics, enzyme inhibitors are more likely to cause side effects such as increased sedation, orthostatic hypotension, or increased risk of akathisia and other extrapyramidal side effects. 

Thioridazine (50 to 100 mg p.o. t.i.d.) is indicated in psychosis. Thioridazine has potent anticholinergic properties and causes heavy sedation. However, it produces a very low incidence of extrapyramidal reactions such as akathisia, dystonia, parkinsonism, tardive dyskinesia, and neuroleptic malignant syndrome. Thioridazine is metabolized to mesoridazine, which is an active antipsychotic (see Table 19). 

If the central antimuscarinic effects caused by the use of antimuscarinic drugs are not clearly recognised for what they are, there is the risk that antipsychotics may be prescribed to treat them. Many antipsychotics also have antimuscarinic adverse effects so that matters are simply made worse. If the patient then demonstrates dystonias, akathisia, tremor and rigidity, even more antimuscarinics may be added to control the extrapy-... 

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