Extrapyramidal symptoms atypical

A metaanalysis showed that 17% to 18% of dementia patients showed a modest treatment response to atypical antipsychotics. Adverse events included somnolence, extrapyramidal symptoms, abnormal gait, worsening cognition, cerebrovascular events, and increased risk of death. 

Use in combination with lithium or valproate for the acute treatment of mania or mixed states Antagonist of postsynaptic DA2 receptors atypical agents also block 5-HT2a receptors that increase the presynaptic release of DA thus lowering the risk of extrapyramidal symptoms and prolactin release... 

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In recent years, the atypical antipsychotic ziprasidone, which is now also available in oral and injectable forms, has superseded haloperidol as the preferred agent when treating the acutely psychotic and agitated patient with dementia.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. 

We prefer low doses of atypical antipsychotics as a first-line treatment. In this way, the threat of extrapyramidal symptoms is largely avoided without having to use a second anticholinergic medication to offset antipsychotic side effects. Risperidone 0.25-0.5mg/day, olanzapine 2.5mg/day, quetiapine 25mg/day, ziprasidone 20mg/day, or aripiprazole 2.5-5mg/day are reasonable starting doses. The typically higher doses used to treat schizophrenia are usually not necessary. 

Finally, many of the atypical antipsychotics act, at least in part, by blocking activity at the serotonin-2 receptor. This may lessen the potential for extrapyramidal side effects and contribute to reducing psychotic symptoms. Atypical antipsychotics... 

From a clinical perspective, an atypical antipsychotic, however, is defined in part by the clinical properties that distinguish such drugs from conventional antipsychotics, namely, low extrapyramidal symptoms and efficacy for negative symptoms. By understanding the difference between blocking dopamine D2 receptors alone... 

Decision/Solution. These initial extrapyramidal symptoms suggested the onset of tardive dyskinesia. The therapist notified the patient s physician, and drug therapy was progressively shifted from haloperidol to the atypical agent clozapine (Clozaril), 450 mg/d. The extrapyramidal symptoms gradually diminished over the next 8 weeks and ultimately disappeared. 

Shirzadi, A. A. Ghaemi, S. N. 2006, Side effects of atypical antipsychotics extrapyramidal symptoms and the metabolic syndrome, Harv.Rev.Psychiatry, vol. 14, no. 3, pp. 152-164. 

The synthesis and discovery of the antipsychotic effects of the piperazinyl-dibenzoazepine, clozapine (Fig. 13.1) and its launch in 1972 was an important turning point in the drug treatment of schizophrenia [1-3]. Clozapine was called an atypical antipsychotic as it did not produce side effects characteristic for compounds of the chlorpromazine- or haloperidol-type (i.e., extrapyramidal symptoms) either in animal models or in the clinic. Its use, however, became very limited when it was recognized that clozapine might cause a severe, and sometimes fatal, form of agranulocytosis. 

In the in-vitro kinetic experiments, the rates of association (Kon) and dissociation (Kan) of various (labeled) antipsychotic compounds to dopamine D2 receptors were determined. Kapur and Seeman found that antipsychotics substantially differ (almost 1000-fold) in their Koff rate (whereas only 10-fold differences were found in the Kon rate), and that this value is highly correlated with their affinity to D2 receptors. These authors also demonstrated that Koff for clozapine, olanzapine and quetiapine was 1.386 min"1, 0.039 min"1, and 3.013 min"1, respectively, and assumed that the rate of how rapidly they left the receptor was an important mechanism in their atypical antipsychotic action. Indeed, this fully explained the lack of extrapyramidal symptoms (EPS) and hyperprolactinemia and the low risk for tardive dyskinesia [34—36]. In this regard, quetiapine (which has the lowest affinity to D2 receptors) seems to be the most atypical among all tested antipsychotics, followed by clozapine and olanzapine (nevertheless, olanzapine s Koff value is close to those of raclopride and chlorpromazine). 

There have been reports of neuroleptic malignant syndrome precipitated by promethazine 100 mg/day to treat neuroleptic drug-induced extrapyramidal symptoms and lorazepam 6 mg/day to treat agitation (349), after the addition of intramuscular haloperidol 23 mg to atypical neuroleptic drugs (350), and in other instances in children and adolescents (351). 

Lewis R. Typical and atypical antipsychotics in adolescent schizophrenia efficacy, tolerability, and differential sensitivity to extrapyramidal symptoms. Can J Psychiatry 1998 43(6) 596-604. 

Amisulpride is an atypical antipsychotic drug, a benza-mide derivative, which may have a low propensity to cause extrapyramidal symptoms (SEDA-22, 55). 

From the perspective of tolerability, these new atypicals are clearly superior to conventionals. The rates of extrapyramidal symptoms, tardive dyskinesia, and anticholinergic effects are much lower. Flowever, as their use has become more commonplace, these drugs appear to have their own adverse effects, some of which have raised substantial concerns. They include increased rates of extrapyramidal symptoms at higher than usual doses, prolactin elevations, and electrocardiogram changes. 

Has atypical antipsychotic properties (i.e., antipsychotic action without a high incidence of extrapyramidal symptoms), especially at low doses, but not a serotonin dopamine antagonist... 

Compared to other atypical antipsychotics with potent serotonin 2A antagonism, amisulpride may have more extrapyramidal symptoms and prolactin elevation, but may still be classified as an atypical antipsychotic, particularly at low doses... 

Extrapyramidal symptoms may be more frequent than with some other atypical anti psych otics... 

Lithium is frequently combined with both traditional and atypical antipsychotics in euphoric acute mania with psychotic features. Case reports of neurotoxicity (e.g., delirium, cerebellar dysfunction, extrapyramidal symptoms, and severe tremors) have been reported in elderly patients receiving lithium and traditional antipsychotics. Combining lithium with calcium channel blockers is not recommended because of reports of neurotoxicity and severe bradycardia with verapamil and diltiazem. Acute neurotoxicity and delirium have been reported in patients receiving ECT with lithinm (even at reduced dosages) therefore lithium should be withdrawn and discontinued at least 2 days before ECT and should not be resumed until 2 to 3 days after the last treatment. 

The dibenzodiazepine clozapine (Table 12-14, X = NH), which is an antischizophrenic, has been approved on a limited basis (1989). Its atypical properties are that it does not bind to DA receptors and, as a result, does not appear to cause extrapyramidal symptoms. It may even reverse tardive dyskinesia. Unfortunately, reports of a high incidence of agranulocytosis severely restricts its use to patients who are refractory to standard antipsychotic medications. Fluperlapine (Table 12-14) is currently being investigated as an alternative... 

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