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.

Successful Management of Clozapine-induced Akathisia with Gabapentin Enacarbil: A Case Report

The management of clozapine (CLZ)-induced adverse events affects patient prognoses. Akathisia is a relatively rare adverse event related to CLZ administration and thus the management of this syndrome is not well established. Here, we report a case of treatment-resistant schizophrenia wherein CLZ-induced akathisia was successfully managed with gabapentin enacarbil (GE). The patient was a 39-year-old woman who had been treated with atypical antipsychotics other than CLZ for three years with poor tolerability. Initiation of CLZ (400 mg/day) attenuated her psychotic symptoms, but was followed by moderate akathisia. Neither benzodiazepines nor biperiden improved the akathisia; however, akathisia was finally diminished with co-administration of GE. GE facilitated a dosage increase in CLZ (450 mg/day) for the improved management of pyschotic symptoms, and thus indirectly contributed to treatment of the patient’s schizophrenia. We suggest that GE is a useful candidate for the management of CLZ-induced akathisia. The improved management of treatment-induced akathisia and other adverse events can extend the potential application of CLZ for treatment-resistant schizophrenia.

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.

Benefical Effects of Sigma-1 Agonist Fluvoxamine for Tardive Dyskinesia and Tardive Akathisia in Patients with Schizophrenia: Report of Three Cases

Fluvoxamine is a selective serotonin reuptake inhibitor that is approved for psychiatric disorders such as major depressive episodes and obsessive-compulsive disorder. Beside inhibition of serotonin reuptake, fluvoxamine is also a potent agonist of endoplasmic reticulum (ER) protein sigma-1 receptors, which play a role in the pathophysiology of a number of psychiatric and neurodegenerative disorders. This report presents beneficial effects of sigma-1 agonist fluvoxamine on hyperkinetic movement disorders such as tardive dyskinesia and tardive akathisia. Fluvoxamine might be a novel treatmet approach in the treatment of hyperkinetic movement disorders.

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.

Prolonged Drug-Drug Interaction between Terbinafine and Perphenazine

I report here an elderly woman receiving perphenazine together with terbinafine. After 1 week of terbinafine treatment she experienced extrapyramidal symptoms and, in particular, akathisia. Her symptoms did not disappear for 6 weeks, and so at 2 weeks prior to this most recent admission she had stopped taking terbinafine. However, these symptoms persisted for 3 weeks after discontinuing terbinafine. It is well known that terbinafine inhibits CYP2D6 and that perphenazine is metabolized mainly by CYP2D6. Thus, when terbinafine and perphenazine are coadministrated, the subsequent increase in the concentration of perphenazine may induce extrapyramidal symptoms. Thus, terbinafine therapy may be associated with the induction and persistence of extrapyramidal symptoms, including akathisia. This case report emphasizes the importance of monitoring drug-drug interactions in patients undergoing terbinafine and perphenazine therapy.

Effective blood transfusion for the symptomatic restless legs syndrome by anemia in the terminal stage of cancer: a case report

We experienced a case in which a blood transfusion proved to be effective for the treatment of symptomatic restless legs syndrome that occurred in a patient demonstrating terminal stage cancer with iron-deficiency anemia due to hemorrhaging as a result of carcinomatous peritonitis. The patient was a female in her seventies who suffered from hepatocellular carcinoma. After undergoing blood transfusion, the symptoms of discomfort in her lower limbs dramatically improved. It was thought that it was expected the symptomatic restless leg syndrome was frequently amalgamated, and a positive diagnosis and appropriate treatment were necessary in the terminal stage of cancer. Palliat Care Res 2011; 6(2): 344-349

Three Cases of Mirtazapine Induced Akathisia

The mirtazapine is a relatively new antidepressant that has noradrenergic and specific serotonin antagonist action(NaSSAs). This has been known as one of the most safest drugs because of its few side effects. Until now, there have been only one case report that mirtazapine causes a EPS side effect(restless leg syndrome). But the peculiar mechanism of this drug makes it impossible to explain the exact reasons why the mirtazapine could induce EPS symptoms. Authors obseved three cases of mirtazapine indeced akathisia. We could not explain the phenomenon the other way except akathisia. So here we presents the three case of mirtazapine induced akathisia and a few possible hypothesis of this phenomenon.

Correlations between Anxious, Depressive Mood and Positive, Negative Symptoms in Chronic Schizophrenics: a Differential Relationship with the Presence of Akathisia / 신경정신의학

OBJECTIVES: In previous studies, the significant correlations between depression-anxiety symptoms and positive symptoms had been reported in schizophrenia. However, it is suggested that these correlations reflect the common influence of third variable, and akathisia-associated dysphoria may be the strong mediator of these relationships. The aim of this study is to investigate the correlations between depression-anxiety symptoms and the schizophrenic symptoms including direct measures of drug-induced akathisia. METHODS: The subjects were 57 patients with chronic schizophrenia. All patients were functioning cognitively at a level to understand and complete the several self-report inventories. Akathisia was rated using Barnes akathisia rating scale (BARS), and depression-anxiety symptoms were assessed by two self-report measures, Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). The symptoms of schizophrenia were assessed using Manchester Scale. RESULTS: In the whole group of subjects, the scores on BDI and dysphoria composite index were significantly correlated with total positive symptom scores and all subscale scores of positive symptoms. In akathisia group, the scores on BDI and dysphoria composite index were still significantly correlated with total positive symptom scores and the subscale scores of delusion. In non-akathisia group, however, there were no significant correlations between self-report depression, anxiety symptoms and total positive symptom scores. CONCLUSION: These results suggest that the akathisia is the important factor in correlations between dysphoric symptoms and positive symptoms. Therefore, the caution is necessary in the interpretation of previous studies which report the direct correlations between depression and positive symptoms. Future research is needed to investigate the associations in akathisia, depression, and the schizophrenic symptom complexes.

Four Cases of Psychoses Suffering from Akathisia and Psychotic Symptoms Effectively Treated with Sanou-shashin-to / 日本東洋医学雑誌

Four patients suffering from akathisia and psychotic symptoms were remarkably improved with Sanou-shashin-to. The first case was a 49-year-old woman with atypical psychosis. The other cases were from twenties to thirties years old women with schizophrenia. All cases were “Jitsu sho” and had constipation. San'o-shashin-to 6.0g (EK-13) a day was administered in all cases and Toukaku-joki-to 7.5g (TJ-61) a day was prescribed in the first case and in the fourth case. In several days, the chief complaint “I can't stand still.” almost disappeared.<br>These cases suggest that San'o-shashin-to involved Rhei Rhizoma (Rhubarb) may be effective for the treatment of akathisia associated with schizophrenia and atypical psychosis and the total dose was decreased by its use because Rhubarb has psychotropic effects and cathartic action.

The Effect of Cyproheptadine Treatment in Neuroleptic Induced Akathisia / 신경정신의학

OBJECTIVE: Neuroleptic Induced Akathisia(NIA) often occurs in neuroleptic treated patients. Cyproheptadine, an antiserotonergic agent, was used to treat neuroleptic induced akathisia. METHOD: In an open trial 21 neuroleptic-treated patients with akathisia were administrated Cyproheptadine(16mg/day) over 4 days. Assessment of akathisia was evaluated using Barnes' rating scale(BAS) for neuroleptic induced akathisia. The degree of depression and psychosis were assessed by brief psychiatric rating scale(BFRS) and Hamilton rating scale for depression(HAM-D). RESULT: Most patients(20 of 21) with neuroleptic induced akathisia(NIA) showed improvement under the treatment of cyproheptadine. There was no aggravation of psychosis or depression during the treatment. Symptoms of akathisia aggravated when cyproheptadine was discontinued. CONCLUSION: Cyproheptadine may be useful in the treatment of neuroleptic induced akathisia(NIA).

There Cases of Extrapyramidal Symptoms Following Fluoxetine / 신경정신의학

The selective serotonin reuptake inhibitor fluoxetine is one of the most frequently prescribed drugs for the treatment of depression and other psychiatric disorders. In the few years, there have been several reports of adverse effects encountered during coadministration of fluoxetine with or without other psychotropic drugs. We experienced three cases of extrapyamidal symptoms were developed when administered fluoxetine alone and with neuroleptics. We conclude that there is a probable or possible causal relationship between fluoxetine and extrapyramidal side effects. The pathogenesis of such adverse reactions, which may be hetero-geneous, is unknown, but it has been suggested that they might be caused by serotonergically mediated inhibition of dopaminergic transmission. From reports in those cases, it appears that fluoxetine alone may be associated with extrapyramidal side reactions. Furthermore the potential for increased levels of concomitant psychotropic medicines and increased side effects, should be borne in mind.