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PURPOSE: The aim of this study was to investigate factors associated with the occurrence of extrapyramidal symptoms (EPS) in users of second-generation antipsychotics (SGA). METHODS: Observational cross-sectional study based on a random sample of subjects from three outpatient clinics. Inclusion criteria were age between 18 and 65 years, of both genders, with a diagnosis of schizophrenia and under the use of a single SGA agent. Subjects who had received i.m. long-acting antipsychotics in the past were excluded. The families of eligible patients were contacted by phone and, if willing to participate in the study, a household visit was scheduled. Informed consent was obtained from all study subjects and their next of kin. The risk of EPS associated with sociodemographic, clinical features and medications used was analyzed by logistic regression. RESULTS: The study population consisted of 213 subjects. EPS were observed in 38.0% of subjects. The more commonly used SGA were olanzapine (76, 35.7%), risperidone (74, 34.3%), quetiapine (26, 12.2%), and ziprasidone (23, 10.8%). Among the drugs used as adjunctive therapy for schizophrenia, benzodiazepines were the most prevalent (31.5%), followed by carbamazepine (24.4%) and antidepressants (20.2%). Multivariate analysis showed that the risk of EPS was associated with the use of carbamazepine (odds ratio 3.677, 95% CI 1.627-8.310). We found no evidence that the type of SGA modified the risk of EPS. CONCLUSION: The occurrence of EPS in SGA users is a common finding, with no difference of antipsychotics studied in relation to the risk of extrapyramidal manifestations. The adjunctive use of carbamazepine may predispose the user of SGA to the occurrence of EPS.

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O autor fez uma extensa revisäo bibliográfica sobre os neurolépticos, em especial o haloperidol, bem como sobre as reaçöes extrapiramidais, com atençäo principal ao parkinsonismo, com descriçäo de quadros e tratamentos indicados

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Antipsychotic drugs are known to block dopamine receptors soon after their administration, resulting in an increase in dopamine neuron firing and dopamine turnover. Nonetheless, antipsychotic drugs must be administered repeatedly to schizophrenics before therapeutic benefits are produced. Recordings from dopamine neurons in rats have revealed that chronic antipsychotic drug treatment results in the time-dependent inactivation of dopamine neuron firing via over-excitation, or depolarization block. Furthermore, the clinical profile of the response to antipsychotic drugs appears to correspond to the dopamine system affected: antipsychotic drugs that exert therapeutic actions in schizophrenics inactivate dopamine neuron firing in the limbic-related ventral tegmental area, whereas drugs that precipitate extrapyramidal side effects cause depolarization block of the motor-related substantia nigra dopamine cells. One factor that remains unresolved with regard to the actions of antipsychotic drugs is the relationship between dopamine turnover and depolarization block--i.e., why does a significant level of dopamine release or turnover remain after antipsychotic drug treatment if dopamine cells are no longer firing? We addressed this question using an acute model of neuroleptic-induced depolarization block. In this model, dopamine cells recorded in rats one month after partial dopamine lesions could be driven into depolarization block by the acute administration of moderate doses of haloperidol. However, similar doses of haloperidol, which were effective at increasing dopamine levels in the striatum of intact rats, failed to change dopamine levels in lesioned rats. This is consistent with a model in which neuroleptic drugs exert their therapeutic effects in schizophrenics by causing depolarization block in DA cells, thereby preventing further activation of dopamine neuron firing in response to external stimuli. Thus, attenuating the responsivity of the dopamine system to stimuli may be more relevant to the therapeutic actions of antipsychotic drugs than receptor blockade or decreases in absolute levels of dopamine, which could presumably be circumvented by homeostatic adaptations in this highly plastic system.

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Os efeitos extrapiramidais dos neurolépticos säo devido a sua açäo no sistema nigro-estriatal, causando aparecimento de desordens diversas, reversíveis e irreversíveis. A mais freqüente é o pseudo-parkinsonismo, e sua origem está em um desequilíbrio acetilcolina-dopamina e é inversamente proporcional à atividade anticolinérgica do medicamento. Na discinesia tardia, ao contrário do que ocorre no pseudo-parkinsonismo, há um aumento da transmissäo dopaminérgica em conseqüência de uma supersensibilidade de desnervaçäo. O tratamento, para o pseudo-parkinsonismo é feito com anticolinérgicos. Näo há, no entanto, consenso no tratamento ideal para a discinesia tardia

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La observación de signos y sintomas similares a la activación extrapiramidal, y la hipotésis que el Clorhidrato de Ketamina podría tener efectos semejantes a los neurolépticos en los núcleos de la base, nos indujo a realizar el presente trabajo, observando los efectos de la Ketamina en ratas sometidas a tratamiento previo con L-Dopa. Se realizaron dos grupos de experimentos. En el primero se administró L-Dopa durante 15 dias, y en el segundo, una dosis única de L-Dopa 24 horas antes del comienzo del experimento. Posteriormente se administró Clorhidrato de Ketamina, comparando los resultados de los grupos pretratados con L-Dopa con los grupos controles. Se observaron los siguientes resultados: el pretratamiento con L-Dopa durante 15 días evitó la aparición de signos motores colaterales indeseables provocados por la Ketamina en las ratas. Estos signos, sin embargo, no desaparecen en el grupo pretratado con una sola dosis. Además en ambos grupos de experimentos se observó que el tiempo de inducción anestésica disminuye, el tiempo de sueño se prolonga y el tiempo de recuperación se acorta. Las diferencias de los resultados de los grupos pretratados con L-Dopa y los grupos controles son estadísticamente significativas. Por último, el pretratamiento con L-Dopa no altera las frecuencias cardiaca y respiratoria en animales anestesiados con Ketamina

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In childhood, several drugs are the cause of acute extrapyramidal syndromes which are true medical emergencies. In the course of one year out of 321 children with acute poisoning, 49 (14.9%) showed these side effects. The responsible drugs were mainly the phenothiazines and haloperidol; only in two cases the metoclopramide. The extrapyramidal syndromes were characterized by akathisia, dyskinesia with dystonic reactions, parkinsonism and akinesia. Diphenhydramine has shown to be useful in treating acute extrapyramidal disturbances when used intravenously followed by oral administration.

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