Evaluation of anticholinergic burden in elderly outpatients and the risk factors / 中南大学学报(医学版)

OBJECTIVES@#The use of anticholinergic drugs in the elderly may lead to negative events such as falls, delirium, urinary retention and cognitive decline, and the higher the number of anticholinergic drugs use, the more such negative events occur. This study aims to analyze the risk factors associated with the prescription of total anticholinergic drugs in elderly outpatients and evaluate the rationality of anticholinergic drugs, and to provide a reference for reducing the adverse effects of anticholinergic drugs.@*METHODS@#A list of drugs with anticholinergic activity based on the Beers criteria was established. The basic information (such as age and gender), clinical diagnosis, and medications of elderly outpatient were extracted from hospital electronic medical records, and the Anticholinergic Cognitive Burden (ACB) Scale was used to calculate the anticholinergic burden for each patient. Logistic regression analysis was used to identify the potential risk factors for the occurrence of problems such as multiple medication and insomnia.@*RESULTS@#A total of 1 840 prescriptions for elderly patients were reviewed. Of these patients, ACB score was more than or equal to 1 in 648 (35.22%) patients. Number of prescription medication (95% CI: 1.221 to 1.336) and insomnia (95% CI: 3.538 to 6.089) were independent factors affecting ACB scores (both P<0.01). Medications for patients of ACB scores were most commonly treated with the central nervous system drugs (such as alprazolam and eszopiclone) and for the cardiovascular system drugs (such as metoprolol and nifedipine).@*CONCLUSIONS@#There is a high rate of ACB drugs use in geriatric patients, and the clinical focus should be on multiple medication prescriptions, especially on the central nervous system drugs (such as alprazolam and eszopiclone) and cardiovascular system drugs (such as metoprolol and nifedipine). The prescription review should be emphasized to reduce adverse reactions to anticholinergic drugs in elderly patients.

Acute angle closure triggered by oral benzodiazepines / Fechamento angular agudo desencadeado por uso oral de benzodiazepínicos

ABSTRACT Benzodiazepines are psychoactive drugs that are prescribed worldwide with limited information on their ocular side effects. Acute angle closure glaucoma is an adverse event with a high risk of blinding, especially in the elderly. We report two patients under 45 years old who presented with bilateral acute angle closure secondary to use of two long half-life benzodiazepines (clonazepam and alprazolam). In addition to suspending the use of these medications and administering ocular hypotensive drugs, both patients were successfully treated with bilateral peripheral laser iridotomy. To the best of our knowledge, this is the first report of bilateral acute angle closure secondary to the use of clonazepam and alprazolam.(AU)

RESUMO Os benzodiazepínicos são medicamentos psicoativos prescritos em todo o mundo, mas com poucas informações sobre seus efeitos colaterais oculares. O glaucoma por fechamento agudo do ângulo iridocorneano é um dos eventos adversos com maior risco de cegueira, sendo descrito particularmente em idosos. Relatamos aqui dois pacientes com menos de 45 anos de idade, com fechamento agudo do ângulo bilateral secundário ao uso de dois diferentes benzodiazepínicos de meia-vida longa (clonazepam e alprazolam). Além da suspensão dessas medicações e do tratamento clínico com drogas hipotensoras oculares, ambos os casos alcançaram sucesso com iridotomias periféricas bilaterais à laser. Considerando o conhecimento atual, estes são os primeiros relatos de fechamento agudo do ângulo bilateral secundária ao uso de clonazepam e alprazolam.(AU)

Estudio comparativo de la calidad biofarmacéutica de Alprazolam 0, 5 mg comercializadas en el mercado peruano / Comparative study of the biopharmaceutical quality of Alprazolam 0. 5 mg commercialized in the Peruvian market

El Alprazolam pertenece a las benzodiazepinas. Sus efectos se atribuyen a que actúa sobre receptores de membrana específicos, lo cual facilita la acción inhibitoria presináptica y postsináptica del ácido γ-aminobutírico (GABA), especialmente en la formación reticular ascendente. Se utiliza para el tratamiento de los estados de ansiedad, crisis de angustia, ataques de pánico y estrés intenso. Este estudio se realizó para analizar los parámetros comparativos de control de calidad in vitro mediante la evaluación de la variación de peso, friabilidad, dureza, tiempo de desintegración, perfil y eficiencia de disolución entre el medicamento innovador (Xanax®) y multifuentes que son comercializados en el mercado peruano. Para realizarlo, se seleccionaron tabletas de Alprazolam 0,5 mg multifuente de diferentes laboratorios comparándolos con el medicamento innovador y se evaluaron las características fisicoquímicas y biofarmacéuticas. Los ensayos farmacopeicos se evaluaron según lo establecido en la USP 42. Los resultados de las pruebas fisicoquímicas indicaron que las muestras analizadas no tenían diferencia significativa y estaban dentro de lo establecido en la farmacopea, así mismo el perfil y eficiencia de disolución permitieron establecer que el comportamiento biofarmacéutico de las mismas era muy similar para ambos tipos de molécula. Se estableció que las tabletas multifuentes de Alprazolam 0,5 mg de esta investigación son bioequivalentes con el innovador, por lo que permite proponer a la comunidad científica la determinación de la equivalencia biofarmacéutica como elemento de apoyo en la toma de decisiones de compra en el servicio farmacéutico

Alprazolam belongs to benzodiazepines. Its effects are attributed to the fact that it acts on specific membrane receptors, which facilitates the presynaptic and postsynaptic inhibitory action of γ-aminobutyric acid (GABA), especially in the ascending reticular formation. It is used to treat anxiety states, panic attacks, and intense stress. This study was carried out to analyze comparative parameters of in vitro quality control by evaluating the variation in weight, friability, hardness, disintegration time, profile and dissolution efficiency between the innovative drug (Xanax®) and multi-sources tablets that are marketed in the Peruvian market. To perform this, Alprazolam 0.5 mg multi-source tablets were selected from different laboratories comparing them with the innovative medicine and the physicochemical and biopharmaceutical characteristics were evaluated. Pharmacopoeial trials were evaluated as established in USP 42. The results of physicochemical tests indicated that analyzed samples did not have a significant difference and were within the established in the pharmacopoeia, as well as the profile and dissolution efficiency allowed to establish that their biopharmaceutical behavior was very similar for both types of molecules. It was established that Alprazolam 0.5 mg multi-source tablets from this research are bioequivalent with innovator, which makes it possible to propose to scientific community determination of biopharmaceutical equivalency as a support element in decision-making process for purchasing services pharmacist

Informação sobre benzodiazepínicos: o que a internet nos oferece? / Information about benzodiazepines: what does the internet offer us?

Resumo Este trabalho analisou a qualidade da informação veiculada na internet sobre 4 benzodiazepínicos amplamente utilizados no Brasil: alprazolam, bromazepam, clonazepam e diazepam. Essa escolha se justifica pelo fato desses medicamentos serem amplamente utilizados, poderem gerar dependência química e a internet ser importante fonte de informação sobre eles. Foram analisados 20 sites para cada medicamento. Mais da metade (56,3%) dos sites foram classificados como deficientes ou muito deficientes. Os problemas mais frequentes foram a ausência da descrição do responsável pelo sítio (60%), informação incompleta (62,5%), ausência de contato para informação adicional (45%) e da última data da atualização (82%). Os resultados reforçam a preocupação com a qualidade da informação em saúde veiculada na internet, já apontada pela literatura, e a necessidade de adoção de critérios mínimos de qualidade para esta informação.

Abstract This study analysed the quality of information published on the internet regarding 4 benzodiazepines that are widely used in Brazil: alprazolam, bromazepam, clonazepam and diazepam. This choice is justified by the fact that these drugs are widely used and can generate chemical dependency, and the internet is an important source of information about them. We analysed 20 sites for each drug. More than half (56.3%) of the sites were classified as deficient or very deficient. The most frequent problems with the sites were the absence of a description of the person responsible for the site (60%), incomplete information (62.5%), the absence of a contact for additional information (45%) and the absence of the last date the site was updated (82%). These results reinforce concerns regarding the quality of the health information published on the internet, which has already been noted in the literature, and the need to adopt minimum quality criteria for this information.

Pharmacological and Neuromodulatory Treatments for Panic Disorder: Clinical Trials from 2010 to 2018

OBJECTIVE: Treatment for panic disorder (PD) have evolved, although there is still a strong unmet need for more effective and tolerable options. The present study summarizes and discusses recent evidence regarding the pharmacological and neuromodulatory treatment of PD. METHODS: MEDLINE, Cochrane Library, PsycINFO and Thomson Reuters’s Web of Science were searched for clinical trials published between 2010 and 2018. We included all prospective experimental studies including randomized controlled trials (RCT) and other clinical trials with more than 10 patients. RESULTS: Only 11 articles met the inclusion criteria, including 4 RCT, 3 open clinical trials and 5 comparative clinical trials. RCT demonstrated efficacy of transcranial magnetic stimulation (TMS) in only one of two trials. Neither pindolol nor d-fenfluramine were effective in blocking flumazenil-induced panic attacks. Augmentation with quetiapine was not superior to placebo. Open trials indicated that escitalopram, vortioxetine and TMS may be effective. Comparative trials did not demonstrate superiority from any drug, but confirmed tranylcypromine, paroxetine, clonazepam and alprazolam as effective options. CONCLUSION: The current study confirmed the efficacy of tranylcypromine, paroxetine, clonazepam, alprazolam and escitalopram. Vortioxetine and TMS, with duration of 4 or more weeks, also seems to be effective. Quetiapine, pindolol and d-fenfluramine were not considered effective compounds.

Intoxicación oral por benzodiacepinas. Reporte de caso y revisión bibliográfica / Oral poisoning by benzodiazepines. Case report and bibliographic review

El alprazolam es un benzodiacepínico de acción intermedia. Su vida media es de 6 a 12 horas. Pocos estudios existen sobre la intoxicación con ésta benzodiacepina. La intoxicación oral por benzodiacepinas (BZD) que se toman en sobredosis sin coadyuvante rara vez causa toxicidad significativa. La presentación clínica clásica de dicha intoxicación incluye depresión del SNC con signos vitales normales. Clínicamente existe disartria, ataxia y alteración del estado mental. El compromiso respiratorio es poco común con las ingestiones orales aisladas, pero se puede observar cuando los pacientes ingieren agentes hipnóticos, sedantes adicionales (como etanol) o cuando los médicos administran BZD como uno de varios agentes para la sedación de procedimiento. Resumen del caso: paciente masculino de 17 años de edad que ingiere oralmente doce tabletas de alprazolam como intento de autolisis. Acude por el servicio de emergencia con somnolencia, enlentecimiento del lenguaje, incoherencia y mareo. Signos vitales estables. Los exámenes complementarios no revelan anormalidad. Se realizan interconsultas a Psicología y Psiquiatría confirmando diagnóstico de depresión mayor, en 72 horas evoluciona favorablemente. Conclusiones: La intoxicación por benzodiacepinas orales de forma aislada rara vez causa depresión respiratoria, descartándose el mito al pensar que una intoxicación oral por benzodiacepinas es igual a depresión respiratoria.

Alprazolam is a benzodiazepine of intermediate action. Its average life is from 6 to 12 hours. Few studies exist about the poisoning of this benzodiazepine. Oral poisoning by benzodiazepines (BZD) that are taken in overdose without adjuvant rarely cause significant toxicity. The classic clinical presentation of such poisoning includes CNS depression with normal vital signs. Clinically there is dysarthria, ataxia and alteration of the mental state. Respiratory compromise is uncommon with isolated oral intakes, but can be seen when patients ingest hypnotic agents, additional sedatives (such as ethanol) or when doctors administer BZD as one of several agents for procedural sedation. Case Summary: a 17-year-old male patient who orally ingests 12 tablets of alprazolam as an attempt at autolysis. He comes for the emergency service with drowsiness, speech slowness, incoherence and dizziness. Stable Vital Signs. The complementary exams do not reveal abnormality. Psychologists and Psychiatrists and social work are consulted, confirming diagnosis of major depression, in 72 hours it evolves favorably. Conclusions: Oral benzodiazepine poisoning in an isolated manner rarely causes respirator depression, so the myth that benzodiazepine poisoning is equal to respiratory depression is ruled out.

Efecto inductor de sueño de Valeriana Officinalis como coadyuvante de Alprazolam en insomnio crónico en adultos. Medicina Complementaria - Trujillo, 2018 / Sleep-inducing effect of Valeriana Officinalis as an adjunct to Alprazolam in chronic insomnia in adults. Complementary Medicine - Trujillo, 2018

Se realizó un estudio cuyo objetivo fue determinar si la terapia de Valeriana officinalis como coadyuvante del alprazolam tiene efecto inductor de sueño en el tratamiento de insomnio crónico, mediante un diseño cuasi experimental en la cual participaron 52 adultos mayores en el Centro de Medicina Complementaria de EsSalud ­ Trujillo, quienes fueron dividido en dos grupos: 26 para el grupo control con terapia de alprazolam (TA) y 26 para el grupo experimental quienes recibieron terapia de valeriana más alprazolam (TB). Se utilizó como instrumento el índice de gravedad de insomnio (ISI) que fue aplicado pre y post tratamiento a ambos grupos. Los resultados evidencian que ambas terapias presentan eficacia, la terapia con alprazolam presentó una reducción de -1.15 puntos del ISI, a diferencia alprazolam más Valeriana oficinales logro una disminución de -3.77. Al comparar ambas alprazolam más valeriana presentó una reducción mayor de 2.62 puntos (p< 0.05). Valeriana Officinalis como coadyuvante del alprazolam tiene efecto inductor de sueño, presentando una diferencia significativa en la reducción del puntaje ISI.

Acupuncture at back- points of five , Geshu (BL 17) and Shenmen (HT 7) for the treatment of menopausal insomnia / 中国针灸

<p><b>OBJECTIVE</b>To compare the clinical efficacy differences between acupuncture at back- points of five , Geshu (BL 17), Shenmen (HT 7) and regular medication for the treatment of menopausal insomnia.</p><p><b>METHODS</b>A total of 128 female patients of menopausal insomnia were randomly divided into an observation group and a control group, 64 cases in each one. Four patients in the observation group and 2 patients in the control group dropped out during the treatment. The patients in the observation group were treated with acupuncture at Feishu (BL 13), Xinshu (BL 15), Pishu (BL 20), Ganshu (BL 18), Shenshu (BL 23), Geshu (BL 17) and Shenmen (HT 7), once a day, and there was an interval of 2 days between every 5 days of treatment. The patients in the control group were treated with oral administration of alprazolam (0.4 mg or 0.8 mg) before sleep. Three-week treatment was taken as one course, and totally three courses were given in the two groups. Pittsburgh sleep quality index (PSQI), levels of estradiol (E), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were observed before treatment and 30 days after treatment; the efficacy was evaluated 30 days after treatment.</p><p><b>RESULTS</b>Each item score and total score of PSQI 30 days after treatment were lower than those before treatment in the two groups (all <0.05), the scores in the observation group were lower than those in the control group (all <0.05). The levels of E 30 days after treatment were higher than those before treatment in the two groups (both <0.05), but the level of FSH and LH 30 days after treatment were lower than those before treatment in the two groups; the level in the observation group was superior to that in the control group (all <0.05). The total effective rate was 98.3% (59/60) in the observation group, which was better than 95.2% (59/62) in the control group (<0.05).</p><p><b>CONCLUSION</b>Acupuncture at Feishu (BL 13), Xinshu (BL 15), Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), Geshu (BL 17), and Shenmen (HT 7) has better efficacy for menopausal insomnia than alprazolam.</p>

Efecto de la pre-medicación con alprazolam por vía oral sobre la presión arterial en pacientes hipertensos en cirugías electivas: un ensayo clínico / Effect of premedication with alprazolam orallyadministered on blood pressure in hypertensive patientsin elective surgeries: a clinical trial

Los ansiolíticos como el alprazolam podrían colaborar en mantener la presión arterial en pacientes hipertensos que deberán someterse a cirugía. El objetivo fue evaluar eficacia de la pre-medicación con alprazolam vía oral para mantener estables cifras de presión arterial en hipertensos programados para cirugías. Ensayo clínico aleatorizado, controlado y a doble ciego. Los pacientes fueron asignados al grupo que recibió alprazolam como premedicación (Grupo A) o al grupo control (Grupo P) que no lo recibió. Se registraron la variación de la presión arterial media (PAM), frecuencia cardíaca (FC) y frecuencia respiratoria (FR) entre el día previo y el día de la cirugía. En el Grupo A se encontró un aumento promedio de la PAM de 0,27 mmHg y en el grupo P de 7,52 mmHg (p= 0,0035). La variación promedio de la FC fue de 2,13 latidos por minuto en el Grupo A y de 5,38 latidos por minuto en el Grupo P (p= 0,0008); y de la frecuencia respiratoria fue de -2,29 respiraciones por minuto en el Grupo A y de -1,18 respiraciones por minuto en el Grupo P (p=0,206).Se halló un aumento significativo de la PAM y la FC en el Grupo P con respecto al Grupo A, no así de la FR. La administración del alprazolam como pre-medicación operatoria evita aumentos significativos de la presión arterial y de la frecuencia cardíaca en los pacientes hipertensos.

Anxiolytics such as alprazolam may help to maintain blood pressure in hypertensive patients who undergo surgery. The aim was to evaluate efficacy of pre-medication with alprazolam orally administered to maintain stable blood pressure in hypertensives programmed for surgeries. Randomized, controlled, double-blind clinical trial. Patients were assigned to the group that received alprazolam as premedication (Group A) or to the control group (Group P) which did not receive it. The variation of the mean arterial pressure(MAP), heart rate (HR) and respiratory rate (RR) were recorded between the day before andthe day of the surgery. In Group A, we found an average increase in MAP of 0.27 mmHgand in the Group P 7.52 mmHg (p = 0.0035). The mean HR variation was 2.13 beats perminute in Group A and 5.38 beats per minute in Group P (p = 0.0008). The mean RR variantion was -2.29 breaths per minute in Group A and -1.18 breaths per minute in Group P (p = 0.206). There was a significant increase in the MAP and HR in Group P compared toGroup A, but not in the RR. The administration of alprazolam as an operative premedication avoids significant increases in blood pressure and heart rate in hypertensive patients.

Consumo de ansiolíticos benzodiazepínicos: uma correlação entre dados do SNGPC e indicadores sociodemográficos nas capitais brasileiras / Consumption of anxiolytic benzodiazepines: a correlation between SNGPC data and sociodemographic indicators in Brazilian capitals

Resumo O objetivo do artigo é conhecer a distribuição e a frequência de consumo de ansiolíticos benzodiazepínicos, bem como avaliar a correlação entre consumo e características demográficas, epidemiológicas, econômicas e sociais. Estudo ecológico tendo como unidade amostral as 27 capitais brasileiras. A coleta de dados foi executada através do banco da Anvisa, para a dispensação do Alprazolam, Bromazepam, Clonazepam, Diazepam e Lorazepam, de 2010 a 2012, do Censo Demográfico 2010 (IBGE), Datasus e da pesquisa Demografia Médica. A análise estatística descritiva e a de regressão linear múltipla foram realizadas para análise dos dados. A região Norte possui as capitais com menores médias de consumo desses medicamentos e o Sudeste as mais elevadas. O consumo médio para a população de todas as capitais foi de 3,60 DHD. O Alprazolam é o mais dispensado pelas farmácias e drogarias particulares, com média de 2,00 DHD para as capitais. A análise de regressão linear múltipla demonstrou que 76% da variância do consumo foi explicada pela variação da densidade demográfica (β = 0,310 p = 0,045) e percentual de médicos (β = 0,507 p = 0,016). O consumo de ansiolíticos de meia vida curta vem crescendo ao longo dos anos, principalmente nas capitais de maior densidade demográfica e concentração de médicos.

Abstract The scope of this article is to determine the distribution and frequency of consumption of anxiolytic benzodiazepines and the correlation between consumption and demographic, epidemiological, economic and social characteristics. It is an ecological study with a sample of 27 state capitals. Data collection was performed through the ANVISA database for the dispensation of Alprazolam, Bromazepam, Clonazepam, Diazepam and Lorazepam in 2010-2012, the 2010 Demographic Census (IBGE), DATASUS and Medical Demographic Research. Descriptive statistical analysis and multiple linear regression analyses were performed for data analysis. The northern region has capitals with the lowest and the southeast has capitals with the highest average consumption of these products. The average consumption for the population of all capitals was 3.60 DHD. Alprazolam is the drug most dispensed by pharmacies and private drugstores with average 2.00 DHD for the capitals. Multiple linear regression analysis showed that 76% of the variation was explained by population density (β = 0.310 p = 0.045) and percentage of physicians (β = 0.507 p = 0.016). The consumption of short half-life anxiolytics has been on the increase, mainly in the cities of greater population density and concentration of physicians.

Potentially Inappropriate Medications by Beers Criteria in Older Outpatients: Prevalence and Risk Factors / 가정의학회지

BACKGROUND: Prescription of inappropriate medicine to elderly patients is a major public health care concern. The Beers criteria have been commonly employed as a screening tool to identify the use of potentially inappropriate medications (PIMs). The present study investigated the prevalence of PIM use according to the Beers criteria as well as factors related to PIM use. METHODS: Data obtained from a retrospective survey included 25,810 outpatients aged ≥65 years from a university medical center in Seoul, Korea. PIMs were defined using the Beers criteria. Factors associated with PIM use were evaluated using multiple regression analysis. RESULTS: Of all participants, 7,132 (27.6%) were prescribed at least one PIM. The most commonly prescribed PIMs were alprazolam (11.2%), clonazepam (10.8%), zolpidem (8.7%), quetiapine (8.4%), and hydroxyzine (5.4%). In multivariate logistic regression analysis, having five or more prescription medicines (odds ratio [OR], 11.32; 95% confidence interval [CI], 9.38 to 13.66) and five or more prescribing doctors (OR, 4.40; 95% CI, 3.59 to 5.39) were strongly associated with PIM. In a likelihood ratio test for trend, an increasing number of medications and prescribing doctors were both significantly associated with PIM. CONCLUSION: At a university medical center, the number of medications and the number of prescribing doctors was associated with PIM in older outpatients.

Potentially Inappropriate Medications by Beers Criteria in Older Outpatients: Prevalence and Risk Factors / 가정의학회지

BACKGROUND: Prescription of inappropriate medicine to elderly patients is a major public health care concern. The Beers criteria have been commonly employed as a screening tool to identify the use of potentially inappropriate medications (PIMs). The present study investigated the prevalence of PIM use according to the Beers criteria as well as factors related to PIM use. METHODS: Data obtained from a retrospective survey included 25,810 outpatients aged ≥65 years from a university medical center in Seoul, Korea. PIMs were defined using the Beers criteria. Factors associated with PIM use were evaluated using multiple regression analysis. RESULTS: Of all participants, 7,132 (27.6%) were prescribed at least one PIM. The most commonly prescribed PIMs were alprazolam (11.2%), clonazepam (10.8%), zolpidem (8.7%), quetiapine (8.4%), and hydroxyzine (5.4%). In multivariate logistic regression analysis, having five or more prescription medicines (odds ratio [OR], 11.32; 95% confidence interval [CI], 9.38 to 13.66) and five or more prescribing doctors (OR, 4.40; 95% CI, 3.59 to 5.39) were strongly associated with PIM. In a likelihood ratio test for trend, an increasing number of medications and prescribing doctors were both significantly associated with PIM. CONCLUSION: At a university medical center, the number of medications and the number of prescribing doctors was associated with PIM in older outpatients.

An Unusual, Paradoxical Arousal with Alprazolam in a Dependant User

No abstract available.

The Efficacy and Safety of Clonazepam in Patients with Anxiety Disorder Taking Newer Antidepressants: A Multicenter Naturalistic Study

OBJECTIVE: This study compared the efficacy and tolerability of clonazepam with other benzodiazepines in patients with anxiety disorders. METHODS: Inclusion criteria were as follows: age >20 years, diagnosis of anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition, text revision (DSM-IV-TR) criteria, taking only one type of antidepressant, and prescribed one of three oral benzodiazepines (alprazolam, clonazepam, or lorazepam). At baseline and week 6, clinical benefit was evaluated using the Clinical Global Impression-Severity Scale (CGI-S), Clinical Global Impression-Anxiety Scale (CGI-anxiety), and Clinical Global Impression-Sleep Scale (CGI-sleep). RESULTS: Among 180 patients, no differences in demographic characteristics among the three benzodiazepine groups were noted. After six weeks of treatment, all benzodiazepine groups showed significant improvements in CGI-S, CGI-anxiety, and CGI-sleep scores (p<0.001). There were no differences in mean changes in CGI-S, CGI-anxiety and CGI-sleep among the three benzodiazepine groups. The incidence of side effects was significantly lower in the clonazepam group than with the other benzodiazepines. The incidences of adverse events for the clonazepam, alprazolam, and lorazepam groups were 26.7% (n=20), 48.4% (n=31), and 43.9% (n=18), respectively. CONCLUSION: The present study suggests that clonazepam is as efficacious as other benzodiazepines for the treatment of various anxiety disorders. Furthermore, the safety profile of clonazepam was superior to the other benzodiazepines in this study.

Tendencias de consumo de medicamentos ansiolíticos e hipnóticos en una población colombiana, 2008-2013 / Trends in the consumption of anxiolytic and hypnotic drugs in a Colombian population

Introducción: En Latinoamérica, los psicofármacos son el tercer grupo de medicamentos más comercializados, especialmente antidepresivos (35%) y ansiolíticos (5%). El objetivo es determinar el comportamiento del consumo y los costos de los ansiolíticos e hipnóticos en una población de pacientes afiliados al Sistema General de Seguridad Social en Salud de Colombia. Material y métodos: Estudio descriptivo observacional. Los datos para el análisis fueron las prescripciones de cualquier ansiolítico o hipnótico, realizadas a pacientes ambulatorios en el periodo comprendido entre enero de 2008 y diciembre de 2013 en una población de 3,5 millones de personas. Se consideraron variables sociodemográficas, farmacológicas, costos globales y costos por mil habitantes y día (CHD). Resultados: El número de pacientes que recibieron los medicamentos estudiados varió de 11.097 a 19.231 entre 2008 y 2013. Los medicamentos más utilizados fueron clonazepam (el 44,1% de las formulaciones), alprazolam (31,2%) y lorazepam (13,2%). El valor facturado de ansiolíticos pasó de 207.673,63 dólares en 2008 a 488.977 dólares en 2013, con un crecimiento del 135,4%. El CHD fue de 0,31 dólares para las benzodiazepinas y 0,02 dólares para los medicamentos Z en 2008 y 0,36 y 0,02 dólares en 2013 respectivamente. Los CHD se redujeron después del año 2010, tras la introducción de medicamentos genéricos. Conclusiones: Los pacientes que reciben benzodiazepinas en Colombia son en su mayoría mujeres, con 55 años de edad promedio, con muy baja frecuencia expresada en CHD comparada con la de otros países.

Introduction: In Latin America, psychotropic medications are the third most marketed drug group, especially antidepressants (35%) and anxiolytics (5%). The objective of this study was to determine the trends in the consumption and the costs of anxiolytic and hypnotic drugs in a population of patients enrolled in the Health System of Colombia. Material and methods: A descriptive, observational study was performed using the data recorded inprescriptions for any anxiolytic or hypnotic drug prescribed to outpatients in the period between January 2008 and December 2013 in a population of 3.5 million people. Sociodemographic, pharmacological variables, overall costs, and cost per thousand inhabitants per day (CHD), were also recorded. Results: The number of patients who received the drugs studied varied from 11,097 to 19,231 between 2008 and 2013. The most used drugs were clonazepam (44.1% of formulations), alprazolam (31.2%), and lorazepam (13.2%). The invoiced value of anxiolytics increased from US$ 207,673.63 in 2008 to US$ 488,977 in 2013, an increase of 135.4%. The CHD was US$ 0.31 for benzodiazepines, and US$ 0.02 for zaleplon, zolpidem and zopiclone (Z drugs) for 2008, and US$ 0.36 and US$ 0.02 in 2013 respectively. The CHD declined after 2010 following the introduction of generic drugs. Conclusions: Patients receiving benzodiazepines in Colombia are mostly women, average age 55 years, with very low frequency in defined daily doses per thousand inhabitants when compared with other countries.

Assessment of Potentially Inappropriate Medication Use in Korean Elderly Patients with Parkinson's Disease

OBJECTIVES: The present study assessed the prevalence of the potentially inappropriate medication (PIM) use in Korean elderly patients with Parkinson's disease. In addition, this study examined risk factors that affect PIM use. METHOD: A retrospective, observational study was conducted using Korean National Health Insurance claims database of 2009. PIM use in Parkinson's disease patients aged 65 years or older was examined based on 2012 Beers Criteria. Multivariable logistic regression was conducted to identify risk factors for PIM use. RESULTS: Among 5,277 elderly patients with Parkinson's disease, 88.9% of patients used PIM(s) at least once. The average number of PIM items used per patient was 4.2. PIM use ratio, the proportion of total amount of PIMs to all medications per patient, was 12.6%. Frequently used PIM therapeutic classes were benzodiazepines (32.7%), first-generation antihistamines (19.2%), and prokinetics (17.5%). Individual PIMs most commonly used included chlorpheniramine (11.4%), levosulpiride (10.9%), diazepam (9.0%), and alprazolam (7.6%). Women (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.11-1.16), medical aid (OR 1.18, 95% CI 1.15-1.21), and long-term facilities (OR 2.43, 95% CI 2.22-2.65) were shown to be risk factors associated with PIM use. Of particular, wide variation in PIM use was associated with the types of healthcare facility. CONCLUSION: The PIM prevalence was very high in elderly Parkinson's disease patients. Nationally effective and systematic efforts to identify and prevent PIM use should be made to ensure patient safety and to improve quality of care in the elderly.

High Prevalence of Psychotropics Overdose among Suicide Attempters in Korea

OBJECTIVE: The availability of suicide methods affects the risk of suicide attempts. This study examined the patterns of substances ingested by suicide attempters (SAs) and the characteristics of SAs using psychotropic overdoses. METHODS: Data for 384 of the 462 eligible SAs who used self-poisoning were analyzed. Demographic variables, clinical characteristics, and factors related to the suicide attempts were examined. RESULTS: There were 256 (66.7%) females and 128 (33.3%) males. Roughly half the SAs ingested psychotropics (n=179, 46.6%). Agricultural chemicals (n=84, 21.9%) were the second most frequently ingested substances, followed by analgesics (n=62, 16.1%), household products (n=27, 7.0%), and other prescribed medications (n=23, 6.0%). Among psychotropics, the most frequently overdosed drugs were sedative-hypnotics, including hypnotics (n=104) and benzodiazepines (n=78). SAs favored Z-drugs and alprazolam. When compared with SAs with non-psychotropic overdoses, significantly more SAs with psychotropic overdoses were female (76% vs. 58.5%, p<0.001) and had a psychiatric history (59.8% vs. 29.8%, p<0.001). They had significantly more previous suicide attempts (0.52+/-1.02 vs. 0.32+/-0.80, p<0.05) and lower risk (7.96+/-1.49 vs. 8.44+/-1.99, p<0.01) and medical severity (3.06+/-0.81 vs. 3.37+/-0.93, p<0.005) scores. CONCLUSION: Psychotropic overdose, especially with sedative-hypnotics, was a major method in suicide attempts. It is important that psychiatric patients are carefully evaluated and monitored for suicidality when prescribing psychotropics.

Use of triazolam and alprazolam as premedication for general anesthesia / 대한마취과학회지

BACKGROUND: Triazolam has similar pharmacological properties as other benzodiazepines and is generally used as a sedative to treat insomnia. Alprazolam represents a possible alternative to midazolam for the premedication of surgical patients. The purpose of this study was to evaluate the anxiolytic, sedative, and amnestic properties of triazolam and alprazolam as pre-anesthetic medications. METHODS: Sixty adult patients were randomly allocated to receive oral triazolam 0.25 mg or alprazolam 0.5 mg one hour prior to surgery. A structured assessment interview was performed in the operating room (OR), the recovery room, and the ward. The levels of anxiety and sedation were assessed on a 7-point scale (0 = relaxation to 6 = very severe anxiety) and a 5-point scale (0 = alert to 4 = lack of responsiveness), respectively. The psychomotor performance was estimated using a digit symbol substitution test. As a memory test, we asked the patients the day after the surgery if they remembered being moved from the ward to the OR, and what object we had shown them in the OR. RESULTS: There were no significant differences between the groups with respect to anxiety and sedation. The postoperative interviews showed that 22.2% of the triazolam-treated patients experienced a loss of memory in the OR, against a 0% memory loss in the alprazolam-treated patients. In comparison with alprazolam 0.5 mg, triazolam 0.25 mg produced a higher incidence of amnesia without causing respiratory depression. CONCLUSIONS: Oral triazolam 0.25 mg can be an effective preanesthetic medication for psychomotor performance.

A Case of Pulmonary Thromboembolism Complicating Acute Overdose of Benzodiazepines

Acute pulmonary thromboembolism (PTE) is a major medical problem in many hospitalized patients with medical and surgical conditions, and venous thromboembolism is responsible for up to 15% of all in-hospital deaths. However, PTE complicating acute intoxication has been reported only rarely, and prophylaxis for venous thromboembolism is not routinely incorporated into the management of acute poisoning in emergency departments or general wards. We describe here a case of pulmonary thromboembolism that developed within 48 h of acute benzodiazepine overdose. A 47-year-old female patient was brought to the emergency department by ambulance. She had been found unconscious, and empty packages of medications prescribed by her psychiatrist and an empty bottle of liquor were found. The estimated drugs and amounts were alprazolam 22.5 mg, diazepam 150 mg, flunitrazepam 7.5 mg, fluoxetine 150 mg, and propranolol 600 mg. Approximately 40 hours after initial presentation, she complained of dyspnea and pulse oxymetry indicated 84%. Her arterial pH was 7.41, pCO2 41.6 mmHg, pO2 46.8 mmHg, and oxyhemoglobin saturation was 83.4%. The serum D-dimer concentration was 2.78 mcg/dL, and computed tomography of the chest showed acute PTE in the right upper lobar and segmental pulmonary arteries and both lower segmental pulmonary arteries. When caring for patients with sedative drug overdose, a high level of suspicion of PTE is required, and appropriate diagnostic and therapeutic measures might be undertaken when PTE is suspected. In addition, appropriate prophylaxis for venous thrombosis should be considered.