Movement Disorders and Mortality in Severely Mentally Ill Patients: The Curacao Extrapyramidal Syndromes Study XIV.

BACKGROUND AND HYPOTHESIS: There is a substantial gap in life expectancy between patients with severe mental illness (SMI) and the general population and it is important to understand which factors contribute to this difference. Research suggests an association between tardive dyskinesia (TD) and mortality; however, results are inconclusive. In addition, studies investigating associations between parkinsonism or akathisia and mortality are rare. We hypothesized that TD would be a risk factor for mortality in patients with SMI. STUDY DESIGN: We studied a cohort of 157 patients diagnosed predominantly with schizophrenia on the former Netherlands Antilles. TD, parkinsonism, and akathisia were assessed with rating scales on eight occasions over a period of 18 years. Twenty-four years after baseline, survival status and if applicable date of death were determined. Associations between movement disorders and survival were analyzed using Cox regression. Sex, age, antipsychotics, antidepressants and benzodiazepines at each measurement occasion were tested as covariates. STUDY RESULTS: Parkinsonism was a significant risk factor with an HR of 1.02 per point on the motor subscale of the Unified Parkinson's Disease Rating Scale (range 0-56). TD and akathisia were not significantly associated with mortality. CONCLUSIONS: Parkinsonism may be an important risk factor for mortality in SMI patients. This finding calls for more follow-up and intervention studies to confirm this finding and to explore whether treatment or prevention of parkinsonism can reduce excess mortality.

Acatisia inducida por antipsicóticos: recomendaciones para la práctica clínica / Antipsychotic-induced akathisia: recommendations for clinical practice

La acatisia es uno de los eventos adversos inducidos por antipsicóticos más prevalentes y puede generar severa angustia en quien lo experimente. Se caracteriza por inquietud psicomotora objetiva y subjetiva. Pertenece al gran paraguas de los "síntomas extrapiramidales", sin embargo, tiene sus particularidades clínicas lo que representa un desafío clínico, tanto en su diagnóstico como en su manejo específico. La presente revisión sintetiza la información disponible a la fecha y ofrece al clínico recomendaciones para prevenir, reconocer y manejar esta complicación frecuente de una de las familias de psicofármacos de mayor prescripción clínica en la actualidad.

Abstract. Akathisia is one of the most prevalent antipsychotic-induced adverse events and causes severe distress in those who experience it. It is characterized by objective and subjective psychomotor restlessness. Usually classified under the great umbrella of extrapyramidal symptoms; however, it has its own clinical peculiarities, which might represent a challenge for the clinician in diagnosis as well as specific management. This review synthesizes the information available to date on antipsychotic-induced akathisia and offers the clinician recommendations to prevent, recognize and treat this prevalent complication of one of the most widely prescribed psychotropic medications today.

Farmacoterapia de la acatisia aguda inducida por neurolépticos / Pharmacological treatment of neuroleptic-induced akathisia

La acatisia aguda es un trastorno del movimiento bastante molesto, caracterizado por sensación subjetiva y signos objetivos de inquietud motora, que se presenta frecuentemente como efecto adverso de los neurolépticos; un tratamiento oportuno es necesario para garantizar una buena adherencia al manejo con antipsicóticos y prevenir recaídas. Se describe el estado actual de los tratamientos disponibles para la acatisia aguda inducida por neurolépticos, valorando efectividad y tolerabilidad. Se realizó una búsqueda electrónica en Pubmed, Science Alert, Springer link, SciELO, Ovid y Elsevier con criterios de selección específicos, obteniendo 87 estudios, de los cuales se escogieron 51 teniendo en cuenta relevancia clínica, nivel de evidencia y actualidad. En este artículo se describen los resultados de la búsqueda. Las benzodiacepinas, los betabloqueadores lipofílicos de acción central y los anticolinérgicos son los fármacos más estudiados para el tratamiento de este trastorno del movimiento; los dos primeros han mostrado superioridad, sin embargo, se necesita aún bastante investigación al respecto.

Acute Akathisia is a movement disorder rather annoying; characterized by subjective feelings and objective signs of restlessness, which often presents as a side effect of neuroleptics, early treatment is necessary to ensure good adherence to treatment with antipsychotics and prevent relapses. To describe the state of the art of available treatments for neuroleptic-induced acute akathisia, taking into account effectiveness and tolerability. An electronic search in Pubmed, Science Alert, Springer link, SciELO, Ovid and Elsevier with specific eligibility criteria, obtaining 87 studies, of which were chosen 51 of them manually, according to their clinical relevance, topicality and level of evidence. In this paper, we describe the results of the search. The benzodiazepines, centrally acting lipophilic beta-blockers and anticholinergics, are the most studied drugs to treat this movement disorder, the first two have shown superiority; however, considerable research is still needed in this regard.

Acatisia inducida por fármacos no psicotrópicos: a propósito de un caso asociado a metoclopramida / Non-psychotropic drugs induced akathisia: a propos of a case associated with metoclopramide use

La metoclopramida es un fármaco antiemético usado en diversas áreas de la práctica médica pero uno de sus efectos adversos más frecuentes y severos es la acatisia. La acatisia es un trastorno del movimiento caracterizado por sensación de intranquilidad y malestar internos acompañados de inquietud motora. Presentamos el caso de un varón de 19 años que desarrolló acatisia aguda luego de la administración de metoclopramida por vía endovenosa. Es importante tener siempre presente en la práctica clínica la posible presentación de acatisia como efecto adverso de la metoclopramida y de otros fármacos no psicotrópicos debido a la frecuencia de su aparición y a su severidad. Realizar un diagnóstico rápido y preciso es necesario para manejar adecuadamente este efecto secundario, además de tomar medidas preventivas para evitar su aparición.

Metoclopramide is an antiemetic drug used in several areas of medical practice but one of its most frequent and severe adverse effects is akathisia. Akathisia is a movement disorder characterized by internal feeling of uneasiness and discomfort accompanied by motor restlessness. We report the case of a 19 year old male who developed acute akathisia after intravenous administration of metoclopramide. It is important in clinical practice to keep in mind the occurrence of akathisia as a posible adverse effect of metoclopramide and other non-psychotropic drugs, because of the frequency of their emergence and severity. It is essential to perform a quick and accurate diagnosis to properly manage this side effect, in addition to taking preventive measures to avoid its occurrence.

The potency and efficacy of anticholinergics to inhibit haloperidol-induced catalepsy in rats correlates with their rank order of affinities for the muscarinic receptor subtypes.

Extrapyramidal syndromes (EPS) caused by antipsychotic therapy are currently treated with anticholinergics that lack selectivity for the five muscarinic receptor subtypes. Since these receptors are heterogeneously expressed among the different classes of striatal neurons and their afferents, it can be expected that their simultaneous blockade will cause distinct, sometimes opposed, effects within the striatal circuitry. In order to test the hypothesis that the differential blockade of the muscarinic receptor subtypes would influence their potency and efficacy to prevent EPS, here we tested four anticholinergics with varying order of affinities for the muscarinic receptor subtypes, and compared their dose-response curves to inhibit haloperidol-induced catalepsy in male rats. Drugs were applied into the lateral ventricle 15 min before haloperidol (2 mg/kg, s.c.). Catalepsy was measured in the bar test at 15 min intervals during 5 h. The preferential M1/M4 antagonist pirenzepine (3, 10, 30, 100, and 300 nmol) caused a dose-dependent inhibition of catalepsy intensity: ED50 = 5.6 nmol [95% CI, 3.9-8.1], and latency: ED50 = 5.6 nmol [95% CI, 3.7-8.6]. Pirenzepine had the steepest dose-response curve, producing maximal inhibition (84 ± 5%) at the dose of 10 nmol, while its effect tended to reverse at higher doses (62 ± 11%). The purported M1/M3 antagonist 4-DAMP (30, 100, and 300 nmol) also caused a dose-dependent inhibition of catalepsy intensity: ED50 = 29.5 nmol [95% CI, 7.0 to 123.0], and latency: ED50 = 28.5 nmol [95% CI, 2.2 to 362.0]. However, the curve for 4-DAMP had a less pronounced slope, reaching its maximal effect (63 ± 14%) at the dose of 300 nmol. The M2/M4 antagonist AF-DX 116 (10, 30, and 300 nmol) only caused a partial inhibition of catalepsy (30 ± 11%) at the dose of 30 nmol, but this changed to a non-significant increment (15 ± 10%) at the dose of 100 nmol. The alleged M4 antagonist tropicamide (30, 100, 300, and 600 nmol) produced a partial inhibition of catalepsy (36 ± 12%) at the dose of 300 nmol, but lacked effect at higher or lower doses. Concurrent treatment with pirenzepine (10 nmol) and tropicamide (300 nmol) produced an effect similar to that of tropicamide alone. The greater potency and efficacy of pirenzepine for catalepsy inhibition could be due to its higher affinity for M1 receptors and, to a lesser extent, for M4 receptors. It is suggested that selective M1 antagonists would be more effective than M2, M3 or M4 antagonists to prevent EPS caused by antipsychotic drugs.

Acatisia associada à bromoprida em um paciente deprimido usando fluvoxamina / Akathisia associated with bromopride in a depressed patient using fluvoxamine

CONTEXTO: A acatisia é definida clinicamente como uma sensação de agitação associada à necessidade de produção de movimentos, comumente deflagrada por bloqueadores dopaminérgicos, como os neurolépticos, podendo ocorrer também durante o tratamento com inibidores seletivos de recaptação de serotonina. É possível que drogas não psiquiátricas que bloqueiem receptores dopaminérgicos, como a bromoprida, possam causar sintomas extrapiramidais. OBJETIVOS: Descrever um desfecho desfavorável caracterizado por acatisia em um paciente depressivo previamente estabilizado com fluvoxamina, após usar bromoprida. MÉTODOS: Descrição de um caso. RESULTADOS: Sr. J., paciente deprimido de 47 anos, estava estabilizado com fluvoxamina 200 mg por dia. Iniciou abruptamente com quadro de inquietação e necessidade de produzir movimentos voluntariamente a fim de aliviar esse desconforto. Há quatro dias havia iniciado o uso de bromoprida 30 mg por dia para tratamento de dispepsia. A suspensão da bromoprida promoveu alívio imediato dos sintomas. CONCLUSÃO: A bromoprida, um bloqueador dopaminérgico, pode ter deflagrado acatisia em um paciente em uso de fluvoxamina. Os mecanismos farmacológicos relacionados a esse desfecho são discutidos.

BACKGROUND: Akathisia is clinically defined as a sensation of restlessness associated to a necessity to produce movements, commonly triggered by dopaminergic blockers, like neuroleptics, and it might occur during treatment with selective serotonine reuptake inhibitors. It is possible that non psychiatric drugs that block dopaminergic receptors, like bromopride, might cause patients to develop extrapyramidal symptoms. OBJECTIVES: To describe an unfavorable outcome clinically characterized by akathisia in a depressed patient previously stabilized with fluvoxamine, after using bromopride. METHODS: Case report. RESULTS: Mr J, 47 year-old depressed patient, had been stabilized with fluvoxamine 200 mg a day. He began abruptly with restlessness and an urgency to produce voluntary movements in order to alleviate such discomfort. Four days earlier he began using bromopride 30 mg a day to treat dyspepsia. Withdrawn of bromopride promoted an immediate relieve of the symptoms. CONCLUSION: Bromopride, a dopaminergic blocker, might have triggered akathisia in a patient using fluvoxamine. The pharmacologic mechanisms regarding this outcome are discussed.