Safety and efficacy of Placida® (fixed dose combination of flupentixol 0.5 mg and melitracen 10 mg) in comparison to escitalopram 10 mg and clonazepam 0.5 mg in patients with comorbid anxiety and depression: a randomized, double blind, double dummy, parallel group clinical trial

Background: Individuals with major depressive disorder (MDD) commonly present with comorbid anxiety and have greater depressive illness severity and chronicity, more suicide attempts, and completions. This randomized, double blind, double dummy, parallel-group clinical phase IV trial (CTRI/2022/11/047050) is aimed to compare the safety and efficacy of Placida® (FDC of flupentixol 0.5 mg + melitracen 10 mg) versus escitalopram + clonazepam in patients with comorbid anxiety and depression. Methods: This is a randomized, controlled, double blind, double dummy, parallel-group, phase IV trial. A total of 440 patients was enrolled across 11 sites in India who fulfilled the inclusion and exclusion criteria. All the subjects will be followed up for 2, 4, 6, 8, 10, 12, 16, 20, and 24 weeks with a buffer period of 1 week in each visit. The patient will be checked for severity of adverse events (AEs) and serious adverse events (SAEs). Efficacy will be assessed using the Hamilton depression rating scale (HAM-D), Hamilton anxiety rating scale (HAM-A) at baseline, weeks 4, 8 and 16, 24 score-reduction rate from baseline to end of treatment and extrapyramidal symptom rating scale (ESRS) at week 16 and end of the study. The first enrolment was done on 26 November 2022 and presently the subjects are under follow-up stage. The anticipated completion date for the study is March 2024. Conclusions: Outcomes of this trial will provide valuable information on safety and efficacy of Placida® as compared to escitalopram and clonazepam in treating patients with comorbid anxiety and depression. Trial Registration: The trial is registered with clinical trial registry India (CTRI/2022/11/047050) prospectively.

Reacción paradojal secundaria a ingesta accidental de benzodiazepinas. Serie de casos / Paradoxical reaction secondary to accidental ingestion of benzodiazepines. Case series

Resumen Globalmente, los fármacos son el tipo de agente más frecuentemente implicado en las intoxicaciones pediátricas y las Ben-zodiacepinas el grupo farmacológico más frecuente. La reacción paradojal, secundaria a la exposición a Benzodiacepinas se caracteriza por la presencia de signosintomatología contraria a los efectos sedativos hipnóticos esperados, pudiendo presentarse con inquietud, ansiedad, hostilidad y alteraciones de la conducta, entre otros. La mayoría de los trabajos hallados acerca de este síndrome en pediatría lo describen secundario a Midazolam endovenoso, en contexto de sedación consciente para la realización de diferentes procedimientos. Las causas por los cuales se puede generar este fenómeno de desinhibición no han sido clarificadas, postulándose tres hipótesis: la desregulación colinérgica central, el aumento del tono gabaérgico en el sistema límbico, tálamo e hipotálamo y el desbalance de serotonina. Se expone una serie de 15 pacientes de entre 1 año y 5 años, expuestos accidentalmente a Benzodiacepinas, principalmente Clonazepam y Lorazepam, a fin de describir las características de esta reacción. En esta serie se observó con latencia breve y duración variable, de hasta 11 horas, la presencia en orden de frecuencia, de: ansiedad, irritabilidad, gritos, hostilidad y conductas agresivas, llanto inconsolable, incapacidad de contención por familiares, conductas irracionales, excitación psicomotriz, desinhibición emocional, alucinaciones y aumento de locuacidad, asociado frecuentemente a ataxia.

Abstract Globally, medicines are the most frequently toxins involved in pediatric poisonings, and Benzodiazepines are the most fre-quent pharmacological group in those poisonings. The paradoxical reaction, secondary to Benzodiazepines exposure, is characterized by the presence of contrary expected sedative-hypnotic effects, and may present with restlessness, increased anxiety, hostility, and behav-ioral alterations, among others. The studies we found about this syndrome in pediatric patients describe it most frequently secondary to endovenous Midazolam, in the context of the conscious sedation to perform different procedures. The reasons why this reaction is generated have not been clarified, three hypotheses are postulated: the central cholinergic dysregulation, the increased Gabaergic tone in the limbic system, thalamus and hypothalamus and the serotonin imbalance. A series of 15 patients, between 1 year and 5 years old, accidentally exposed to Benzodiazepines, mainly Clonazepam and Lorazepam, to describe the characteristics of the paradoxical reaction secondary to Benzodiazepines exposure. In this case series, we observed with short latency and variable duration, up to 11 hours, the presence in order of frequency of: anxiety, irritability, screams, hostility and aggressive behaviors, inconsolable crying, inability to con-tain by their family members, irrational behaviors and psychomotor excitement, emotional disinhibition, hallucinations and increased talkativeness, frequently associated with ataxia.

Prescripción de clonazepam tabletas en el municipio Santa Clara

Introducción: Las benzodiazepinas son medicamentos utilizados para el tratamiento de la ansiedad y los trastornos del sueño, así como relajantes musculares y anticonvulsivantes. A pesar de que no se aconseja su uso para tratamientos prolongados, algunos pacientes lo utilizan de forma continuada lo cual se asocia con la dependencia física y síntomas de abstinencia moderada a severa. El clonazepam es uno de las benzodiazepinas con propiedades ansiolíticas y antiepilépticas. Objetivo: Determinar el aumento en la prescripción del medicamento clonazepam de 1mg tabletas en el municipio Santa Clara. Métodos: Se realizó una investigación observacional, retrospectiva, descriptiva y transversal, que se correspondió con un estudio de uso de medicamentos, del tipo prescripción-indicación del medicamento clonazepam de 1mg tabletas, durante el período junio 2021 a junio 2023. El universo lo conformaron 5 819 pacientes que constituían la totalidad de los pacientes de tipo ambulatorio con dicha prescripción al final del estudio. Resultados: En cuanto al sexo, al final del estudio, la distribución mostró un predominio del sexo femenino. Se evidenció un incremento de un 198 % de los pacientes y predominó el grupo de edades de más de 59 años (55,3 %). Conclusiones: Existe una alta tendencia en el uso del clonazepam, sobre todo en personas de la tercera edad, las cuales son las más susceptibles a la aparición de efectos indeseables con consecuencias lamentables.

Introduction: Benzodiazepines are drugs used for anxiety and sleep disorders, as well as muscle relaxants and anticonvulsive. Despite being discouraged in prolonged treatments, some patients have chronic use, which is associated with the development of physical dependence, manifested in moderate to severe withdrawal symptoms. Clonazepam is one such benzodiazepine which has antiepileptic as well as anxiolytic properties. Objective: To determine the increase in prescription of clonazepam 1mg tablets in Santa Clara municipality. Methods: An observational, retrospective, descriptive and cross-sectional investigation was carried out, which corresponded with a medications use study, of prescription-indication type. It was conducted aimed at assessing the prescription of the medication clonazepam 1mg tablets during the period from June 2021 to June 2023. The universe was built by 5819 patients which constituted the totality of ambulatory patients with such prescription at the end of the study. Results: Regarding sex, at the end of the study, the distribution showed a predominance of the female sex. It was evidenced an increase of 198 % of patients and a predominance of patients over 59 years of age (55.33 %). Conclusions: The results showed a high trend in the use of clonazepam, mainly in elderly patients, which are the most susceptible to the appearance of undesirable effects and unfortunate consequences.

Elaboração e validação do protocolo de desprescrição do clonazepam em idosos / Elaboration and validation of clonazepam deprescribing protocol for the elderly / Elaboración y validación del protocolo de desprescripción del clonazepam en ancianos

Introdução: Algumas alterações fisiológicas que ocorrem no indivíduo idoso favorecem o acúmulo e a intoxicação por medicamentos. Dentre estes, podemos citar a classe dos benzodiazepínicos, medicamentos que, apesar de amplamente prescritos, principalmente para tratamento de distúrbios do sono e ansiedade, são considerados potencialmente inapropriados para o uso em idosos. Portanto, a elaboração de protocolos para desprescrição desses medicamentos é estratégia necessária na gestão do cuidado dos pacientes geriátricos. Objetivo: Elaborar e validar um protocolo de desprescrição do clonazepam para idosos que fazem uso deste medicamento para ansiedade ou insônia. Métodos: Estudo metodológico, desenvolvido em duas etapas, sendo elas a elaboração e a validação do protocolo de desprescrição do clonazepam para idosos que fazem uso desse medicamento para ansiedade ou insônia, excetuando-se aqueles que preenchem os critérios de exclusão. A elaboração do protocolo resultou em três produtos: um fluxograma de desprescrição, um folheto sobre higiene do sono e um folheto contendo os benefícios da desprescrição do clonazepam sob supervisão médica. A validação do protocolo foi realizada por médicos especialistas, por meio da Técnica de Delphi. Já na validação dos folhetos, participaram, além dos especialistas, indivíduos com 60 anos ou mais, de ambos os sexos, que não fizessem uso do clonazepam. A partir dos resultados obtidos, foi analisada a concordância da avaliação por meio do Coeficiente de Validade de Conteúdo (CVC), uma vez que essa ferramenta objetiva medir o grau de concordância dos juízes participantes do processo de validação. Resultados: O fluxograma foi considerado validado após a segunda rodada de avaliação, pois todos os itens avaliados obtiveram CVC igual ou superior a 0,8 nesta rodada. Os folhetos foram considerados validados já na primeira rodada de avaliação, pois todos os itens também obtiveram CVC superior a 0,8 durante esta rodada. Conclusão: Considerando os resultados obtidos, o protocolo se apresenta como uma ferramenta importante ao guiar a conduta médica no processo de desprescrição do clonazepam.

Introduction: Some physiological changes that occur in the elderly individual favor the accumulation and intoxication by drugs. Among these, we can mention the class of benzodiazepines, medicines which, although widely prescribed mainly for the treatment of sleep disorders and anxiety, are considered potentially inappropriate for use in the elderly. Therefore, the elaboration of protocols for the deprescribing of those drugs is a necessary strategy in the management of the care of geriatric patient. Objective: To elaborate and validate a protocol for the Deprescribing of clonazepam for the elderly who use this medication for anxiety or insomnia. Methods: Methodological study, developed in two stages ­ elaboration and validation of the protocol of deprescribing of clonazepam for elderly people who use this medication for anxiety or insomnia, except those who meet the exclusion criteria. The elaboration of the protocol resulted in three products: a flowchart of deprescribing, a leaflet of sleep hygiene, and a leaflet containing the benefits of the clonazepam Deprescribing under medical supervision. The validation of the protocol was performed by medical specialists, through the Delphi Technique. In addition to the specialists, individuals of both sexes, aged 60 years or more who did not use clonazepam, took part in the validation of the leaflets. Based on the results obtained, the agreement of the evaluation was analyzed using the Content Validity Coefficient (CVC), since this tool aims to measure the degree of agreement of the judges participating in the validation process. Results: The flowchart was considered validated after the second round of evaluation, since all items assessed had a CVC equal to or greater than 0.8 in this round. The leaflets were considered validated in the first evaluation round, since all items also obtained CVC greater than 0.8 during this round. Conclusion: Considering the results obtained, the protocol presents itself as an important tool in guiding medical conduct in the process of Deprescribing of clonazepam

Introducción: Algunas alteraciones fisiológicas que ocurren en el individuo mayor favorecen el acumulación y la intoxicación por medicamentos. Entre estas, podemos citar la clase de los benzodiazepínicos, medicamentos que, a pesar de ampliamente prescritos, principalmente para el tratamiento de disturbios del sueño y de la ansiedad, son considerados potencialmente inapropiados si usados por personas mayores. Por lo tanto, la elaboración de protocolos para desprescripción de esos medicamentos son estrategias necesarias en la gestión al cuidado de los pacientes geriátricos. Objetivo: Elaborar y validar un protocolo de desprescripción de clonazepam para mayores que hacen uso de esta medicina para ansiedad o insomnio. Métodos: Estudio metodológico, desarrollado en dos etapas, siendo ellas la elaboración y la validación del protocolo de desprescripción del clonazepam para mayores que hacen uso de ese medicamento para ansiedad o insomnio, exceptuando aquellos que cumplen los criterios de exclusión. La elaboración del protocolo resultó en tres productos: un flujograma de desprescripción, un folleto sobre la higiene del sueño y un folleto conteniendo los beneficios de la desprescripción del clonazepam bajo supervisión médica. La validación del protocolo fue realizada por médicos especialistas, por medio de la Técnica de Delphi. Ya en la validación de los folletos, participaron, además de los especialistas, individuos con 60 años o más, de ambos sexos, que no hiciesen uso de clonazepam. A partir de los resultados obtenidos, fue analizada la concordancia de la evaluación por médio del Coeficiente de Validez de Contenido (CVC), una vez que esa herramienta objetiva medir el grado de concordancia de los jueces partícipes del proceso de validación. Resultados: El flujograma fue considerado validado después de la segunda ronda de evaluación, pues todos los ítems evaluados obtuvieron CVC igual o superior a 0,8 en esta rodada. Los folletos fueron considerados validados ya en la primera rodada de evaluación, pues todos los ítems también obtuvieron CVC superior a 0,8 durante esta rodada. Conclusión: Considerando los resultados obtenidos, el protocolo se presenta como una herramienta importante al guiar la conducta médica en el proceso de desprescripción del clonazepam.

Consumo do benzodiazepínico clonazepam (Rivotril®) no estado do Rio de Janeiro, Brasil, 2009-2013: estudo ecológico / Consumption of the benzodiazepine clonazepam (Rivotril®) in Rio de Janeiro State, Brazil, 2009-2013: an ecological study

Resumo O objetivo do estudo é estimar a prevalência do uso de clonazepam no Estado do Rio de Janeiro (RJ). Estudo ecológico e descritivo do consumo de clonazepam (2009-2013), com dados do Sistema Nacional de Gerenciamento de Produtos Controlados da Anvisa. O consumo foi medido pela Dose Diária Definida, com indicadores por população total e com 18 anos e mais utilizando a DDD padronizada de 8mg (anticonvulsivante) e a de 1mg (hipnosedativo). Os Municípios da Região Metropolitana foram agrupados segundo os Índices de Desenvolvimento Humano (IDH) e de GINI, submetidos à análise de conglomerados e apresentados segundo o consumo de clonazepam. No Estado do RJ, o consumo entre 2009 e 2013 aumentou de 0,35 para 1,97 DDD/1000 habitantes. Os valores são maiores para os indivíduos acima de 18 anos. Empregando-se 1mg ao invés de 8mg, chega-se a 21 DDD/1000 habitantes acima de 18 anos, em 2013. Rio de Janeiro e Niterói, com os maiores IDH, apresentaram em 2013 os maiores consumos, 3,38 e 4,52 DDD, respectivamente. Os dados sugerem que até 2% da população adulta é usuária de clonazepam, possivelmente como hipnosedativo. Deve-se atentar para o uso ampliado e fora de indicações terapêuticas, dados o potencial de abuso e as reações adversas ao clonazepam.

Abstract This descriptive, ecological study of clonazepam consumption in Rio de Janeiro State (RJ) estimated use prevalence from 2009 to 2013 using data from the National Controlled Product Management System operated by Brazil's health surveillance agency, Anvisa. Consumption was measured by total population and by population over 18 years old, using the standardised Daily Defined Doses of 8 mg (anticonvulsant) and 1 mg (sedative-hypnotic). The municipalities of the Rio de Janeiro Metropolitan Region were grouped by Human Development Index (HDI) and GINI index, subjected to cluster analysis and ranked by clonazepam consumption. From 2009 to 2013, consumption in the state rose from 0.35 to 1.97 DDD/1000 population, but the figures are higher for individuals over 18 years of age. A DDD of 1 mg instead of 8mg returns consumption in 2013 of 21 DDD/1000 population over 18 years of age. Consumption in 2013 was highest - 3.38 and 4.52 DDD, respectively - in Rio de Janeiro and Niterói, which have the highest HDIs. This suggests that up to 2% of the adult population uses clonazepam, possibly as a sedative-hypnotic. This broad use and use outside therapeutic indications deserves attention, given clonazepam's potential for abuse and adverse reactions.

The case of chronic clonazepam use in Rio de Janeiro through the voices of users / El caso de uso crónico de clonazepam en Río de Janeiro en la voz de los usuarios / O caso do uso crônico de clonazepam no Rio de Janeiro pela voz dos usuários

Abstract: In Brazil, Rivotril® (clonazepam) has gained a reputation as a social object. Its logo is emblazoned on everyday objects and the drug itself is the topic of online communities and featured on television programs. Method. We conducted in-depth, semi-structured interviews with a sample of adults (aged 18 and over) who lived in the state of Rio de Janeiro and who had been using Rivotril® for over 12 months. Using the snowball technique, we collected an unintentional sample of 20 subjects over 18 years of age who lived in Rio de Janeiro and who had been using the drug continuously for at least 12 months. Researchers presented the project to their social contacts, sending them emails in which they invited them to indicate people who fitted the inclusion criteria. Results. The key points of the analysis were: 1) the users developed "lay expertise" on the dosage of the drug; 2) whenever treatment was supervised by a psychiatrist, an antidepressant was prescribed together with the benzodiazepine; 3) once they started using clonazepam, the users' perception of their capacity to live without it changed; 4) although all the interviewees were long-term users, they did not see themselves as dependent on the drug. Discussion. The users customized, negotiated, and legitimized their use of clonazepam, from how much and how often they took it to their habits of sharing it. Further research investigating users' accounts of prescription drugs are needed to include their perceptions, which are frequently overlooked in the field of analysis.

Resumen: En Brasil, el Rivotril® viene recibiendo destaque como objeto social. El logotipo de su marca aparece en diversos objetos de uso cotidiano, además de ser asunto en comunidades virtuales y programas de televisión. Métodos. Utilizamos la técnica de muestreo de bola de nieve y realizamos entrevistas de tipo semiestructuradas en profundidad en una muestra conformada por 20 individuos mayores de 18 años, residentes en el estado de Río de Janeiro, que habían hecho uso de Rivotril® por por un periodo mayor a 12 meses. Los investigadores presentaron el proyecto en sus redes sociales, y enviaron e-mails solicitando la indicación de potenciales usuarios interesados en participar de la investigación. Resultados. Entre los puntos analiticos destacamos: 1) los usuarios desarrollaron un conocimiento lego sobre dosis; 2) cuando el tratamiento fue prescripto por psiquiatra, siempre incluyó también la prescripción de un antidepresivo junto al benzodiazepínico, 3) una vez iniciado el uso del clonazepam, la percepción de la capacidad de los pacientes de vivir sin ese medicamento se vió alterada; 4) a pesar de tratarse de usuarios cronicos, no se autoperciben como dependientes de la sustancia. Discusión. Los usuarios personalizaban, negociaban y legitimaban el uso de la sustancia, desde la cantidad, frecuencia y prácticas de compartirla. Nuevas investigaciones que incorporen relatos de usuarios de sustancias prescriptas deben ser realizadas, con el objetivo de incluir las percepciones de los propios usuarios, frecuentemente desconsideradas del campo de análisis.

Resumo: No Brasil, o Rivotril® tem recebido destaque como objeto social. O logotipo da marca aparece estampado em objetos de uso cotidiano, além de o medicamento ser assunto de comunidades virtuais e programas televisivos. Método. Utilizamos a técnica da bola de neve para chegar aos usuários e realizamos entrevistas em profundidade, com roteiro semiestruturado com uma amostra de 20 pessoas maiores de 18 anos, residentes no Estado do Rio de Janeiro, que utilizaram o medicamento por mais de 12 meses. Os pesquisadores apresentaram o projeto e enviaram e-mails para suas redes de contato social, solicitando que indicassem potenciais usuários interessados em participar da pesquisa. Resultados. Dentre os pontos analíticos, destacam-se: 1) os usuários desenvolveram uma "expertise leiga" sobre as dosagens; 2) sempre que o tratamento era supervisionado por um psiquiatra, um antidepressivo era prescrito junto com o benzodiazepínico; 3) uma vez iniciado o uso do clonazepam, a percepção de sua capacidade de viver sem o medicamento se alterava; 4) embora se tratassem de usuários de longo-prazo, eles não se percebiam como dependentes da substância. Discussão. Os usuários customizavam, negociavam e legitimavam o uso da substância, desde a quantidade, a frequência e as práticas de compartilhamento. Mais pesquisas que investiguem o relato de usuários de substâncias prescritas deve ser realizados, no intuito de incluir as percepções dos usuários, que são frequentemente desconsiderados do campo de análise.

Antimyoclonic Effect of Levetiracetam and Clonazepam Combined Treatment on Myoclonic Epilepsy with Ragged-Red Fiber Syndrome with m.8344A>G Mutation / 中华医学杂志(英文版)

<p><b>Background</b>Treatment of myoclonic seizures in myoclonic epilepsy with ragged-red fibers (MERRFs) has been empirical and ineffective. Guideline on this disease is not available. Additional trials must be conducted to find more suitable treatments for it. In this study, the antimyoclonic effects of monotherapies, including levetiracetam (LEV), clonazepam (CZP), valproic acid (VPA), and topiramate (TPM) compared to combination therapy group with LEV and CZP on MERRF, were evaluated to find a more advantageous approach on the treatment of myoclonic seizures.</p><p><b>Methods</b>Treatments of myoclonic seizures with VPA, LEV, CZP, and TPM were reported as monotherapies in 17 MERRF patients from Qilu Hospital between 2003 and 2016, who were diagnosed through clinical data and genetic testing. After 1-4 months of follow-up (mean: 82.9 ± 28.1 days), 12 patients that exhibited poor responses to monotherapy were given a combined treatment consisting of LEV and CZP subsequently. The follow-up period was 4-144 months (mean: 66.3 ± 45.3 months), the effective rates of monotherapy group (17 patients) and combination therapy group (12 patients) were analyzed by Chi-square test.</p><p><b>Results</b>The m.8344 A>G mutation was detected in all patients. There were four patients with partial response (4/17, two in the CZP group and two in the LEV group), ten patients with stable disease (10/17, six in the CZP group, three in the LEV group, and one in the TPM group), and three patients with progressive disease (3/18, two in the VPA group and one in the TPM group). Twelve of the patients with LEV combined with CZP showed a positive effect and good tolerance (12/12), eight of them demonstrated improved cognition and coordination. There was a significant difference between the monotherapy group and combination therapy group in the efficacy of antimyoclonic seizures (χ = 13.7, P < 0.001).</p><p><b>Conclusions</b>LEV in combination with CZP is an efficient and safe treatment for myoclonic seizures in patients with this disease exhibiting the m.8344A>G mutation.</p>

Postmenopausal Burning Mouth Syndrome Relieved by Clonazepam

Burning mouth syndrome (BMS) is an intraoral chronic pain disorder characterized by continuous burning sensations. BMS occurs particularly in postmenopausal women, and its etiology is not definite and considered idiopathic. Various treatments such as analgesics, anticonvulsants, and antidepressants are found to be effective, but the definitive treatment has not been established. We report two cases of postmenopausal BMS that were relieved by clonazepam, and review the literature about the various possible etiologies and treatment modalities of BMS.

The Role of Segmental Analysis of Clonazepam in Hair in Drug Facilitated Cases / 法医学杂志

OBJECTIVES@#To infer the frequency of dosage and medication history investigate of the victims in drug facilitated cases by the segmental analysis of clonazepam in hair.@*METHODS@#Freezing milling under liquid nitrogen environment combined with ultrasonic bath was used as sample pretreatment in this study, and liquid chromatography-tandem mass spectrometry was used for the segmental analysis of the hair samples collected from 6 victims in different cases. The concentrations of clonazepam and 7-aminoclonazepam were detected in each hair section.@*RESULTS@#Clonazepam and its metabolite 7-aminoclonazepam were detected in parts of hair sections from the 6 victims. The occurrence time of drug peak concentration was consistent with the intake timing provided by victims.@*CONCLUSIONS@#Segmental analysis of hair can provide the information of frequency of dosage and intake timing, which shows an unique evidential value in drug facilitated crimes.

The Role of Segmental Analysis of Clonazepam in Hair in Drug Facilitated Cases / 法医学杂志

Objective T o infer the frequency of dosage and m edication history investigate of the victim s in drug facilitated cases by the segm ental analysis of clonazepam in hair. Methods Freezing m illing un-der liquid nitrogen environm ent com bined w ith ultrasonic bath w as used as sam ple pretreatm ent in this study, and liquid chrom atography-tandem m ass spectrom etry w as used for the segm ental analysis of the hair sam ples collected from 6 victim s in different cases. T he concentrations of clonazepam and 7-am in-oclonazepam w ere detected in each hair section. Results C lonazepam and its m etabolite 7-am inoclon-azepam w ere detected in parts of hair sections from the 6 victim s. T he occurrence tim e of drug peak concentration w as consistent w ith the intake tim ing provided by victim s. Conclusion Segm ental analysis of hair can provide the inform ation of frequency of dosage and intake tim ing, w hich show s an unique evidential value in drug facilitated crim es.

Clonazepam associated hypothyroidism: Aforethought on a concealed dilemma.

Subclinical hypothyroidism or mild thyroid failure is a familiar problem, with a prevalence of 3-15% in a population without any known overt thyroid disorder. The prevalence increases with age and is relatively higher among females. Subclinical hypothyroidism is defined as serum thyroid stimulating hormone (TSH) levels above the upper limit of normal (4 mU/L) while the triiodothyronine (T3) and thyroxine (T4) enduring within the normal range. Additionally, there exists a log-linear relationship between TSH and circulating T3 and T4; hence, measurement of serum TSH becomes mandatory for diagnosing mild thyroid failure when free T3and T4 are lying within normal limits. Though, autoimmune thyroid disease is the most common cause for elevated TSH; thyroid functions can be afflicted by long-term consumption of drugs like lithium, amiodarone. The causal relationship between benzodiazepine class of drugs, particularly clonazepam and subclinical hypothyroidism has never been established clinically, yet there are some pre-clinical studies to claim the effect of benzodiazepine on thyroid functions; operating at various levels – hypothalamus, thyroid gland, peripheral cells and nuclear receptors. Henceforth, we would like to report a rare occurrence of subclinical hypothyroidism in an elderly female receiving clonazepam for her underlying psychiatric illness.

Clinical study of sleep related rhythmic movement disorder / 中华神经科杂志

Objective To discuss the clinical and electrophysiological characteristics of sleep related rhythmic movement disorder ( SRMD).Methods We studied the clinical and electrophysiological characteristics of 3 patients diagnosed as SRMD in the Electroencephalography Monitoring Center of Xijing Hospital, Xi′an, China.The 3 patients accorded with diagnostic criteria of SRMD that international classification of sleep disorders-3 edition recommended and were followed up for more than 1 year.Results These 3 male patients were ranging from 6 to 27 years old.The onset age of the patient 1 was 13 years,and the others were 1 year old.The patient 2 became symptom-free at the age of 7.The patient 3 relieved at 2-year-old, but recurred at the age of 21. There was no epileptic seizure discharge in video-electroencephalography of the 3 patients, but synchronous electromyography changes during the attack were mistaken for slow wave.Video-polysomnography showed that numbers of awakenings and arousals index were high.Two patients were treated with clonazepam.One had an obvious curative effect, the other had marked efficacy until added trazodone.Conclusions SRMD can occur not only in infants, but also in adolescents and adults.Patients who have the problems of the sleep quality should be treated.Clonazepam can obviously relieve symptoms and improve sleep quality.Patients who do not have a good effect with clonazepam can try to add trazodone.Video-electroencephalography monitoring and interpreting it correctly are important to the diagnosis of paroxysmal disease.

Clinical Observation of Chaihu Shugan Powder Combined with Clonazepam in the Treatment of Liver Qi Stagnation Type Anxiety / 中国药房

OBJECTIVE:To observe clinical efficacy and safety of Chaihu shugan powder combined with clonazepam in the treatment of liver qi stagnation type anxiety. METHODS:96 patients with liver qi stagnation type anxiety were randomly divided in-to observation group and control group,with 48 cases in each group. Control group was given Clonazepam tablet with initial dose of 0.5 mg,increasing to 4.0 mg gradually,tid;observation group was additionally given Chaihu shugan powder 300 ml,bid,on the basis of control group. Both groups were treated for 6 weeks. Clinical efficacy of 2 groups were observed,and HAMA and SAS were observed before and after treatment;the incidence of ADR were compared between 2 groups. RESULTS:The total effective rate of observation group(97.92%)was significantly higher than that of control group(83.33%),with statistical significance(P0.05);HAMA and SAS of 2 groups decreased significantly 1,3 and 6 weeks after treatment,and the observation group was lower than the control group, with statistical significance(P0.05). CONCLUSIONS:Chaihu shugan powder combined with clonazepam is effective,improve patient anxiety and safe in the treatment of liver qi stagnation type anxiety.

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.

A Case of Aerophagia Diagnosed by Multichannel Intraluminal Impedance Monitoring / 대한소화기학회지

Aerophagia is a disorder caused by abnormal accumulation of air in the gastrointestinal tract as a result of repetitive and frequent inflow of air through the mouth. For the diagnosis of this condition, it is difficult to objectively measure the air swallowing. However, multichannel intraluminal impedance monitoring facilitates the differential diagnosis between normal air swallowing and pathologic aerophagia, and can aid in the determination of the frequency and amount of air swallowed. In this report, in addition to a literature review, we describe a case of 36-year-old man with abdominal distension who was diagnosed with aerophagia using esophageal impedance monitoring and was treated with clonazepam.

Simultaneous determination of clomipramine and four benzodiazepines in human plasma by HPLC-DAD after solid phase extraction / 中国药理学通报

Aim To establish a novel,highly sensitive,rapid and cost-effective HPLC method to simultaneously determine tri-cyclic antidepressant clomipramine and four benzodiazepines of diazepam,alprazolam,clonazepam,oxazepam in human plasma pretreated by solid phase extraction.Methods The assay was achieved by using C8 column (4.6 mm ×1 50 mm,5 μm)kept at 45 ℃,mobile phase 73.2:26.8 V/V (50 mmol·L -1 ,pH 3.0 phosphate buffer:acetonitrile)with flow rate of 1 .2 ml· min -1 ,and UV detection was set at λ220 nm.Solid phase ex-traction was performed on C1 cartridges.Results The calibra-tion curve was demonstrated to be linear (r >0.9994)in the ranges of 5 ~200 μg·L -1 for alprazolam and clonazepam,1 0 ~500 μg·L -1 for diazepam,20 ~500 μg· L -1 for clomipra-mine,and 7.5 ~2000 μg·L -1 for oxazepam;the limit of detec-tion (LOD)was 1 .5,1 .4,3.0,5.5 and 2.2 μg·L -1 for al-prazolam,clonazepam,diazepam,clomipramine and oxazepam respectively.Intra-day and inter-day precision revealed a coeffi-cient of variation of 2.2% ~1 2.6% and 2.1 % ~1 3.2%,re-spectively.Extraction yield ranged from 81 .1 % ~1 00.1 % for all analytes.Conclusion The developed method is accurate, reproducible,convenient,and suitable for routine therapeutic drug monitoring of clomipramine and the four benzodiazepines.

Clonazepam Treatment of Pathologic Aerophagia in Children with Mental Retardation / 대한소아소화기영양학회지

PURPOSE: Pathologic aerophagia (PA) may lead to bowel perforation or volvulus in mentally retarded patients. The authors investigated the effects of clonazepam on the management of PA in children with severe to profound mental retardation (MR). METHODS: This study was undertaken as a retrospective case analysis of 21 PA patients with MR who were followed for over 12 months and diagnosed as having PA. Patients were assigned to two management groups, that is, to a clonazepam randomized open-labeled, treatment group or a reassurance group. The following were recorded and analyzed; age, response, remission rate to clonazepam treatment, and the side effect of clonazepam. It was defined positive response (response+) as being symptom-free for a whole week within 1 month of commencing treatment and remission(+) as being symptom-free for a whole month within 6 months of treatment. RESULTS: The average age of the 21 PA children with MR was 10 years and 13 patients were female. Symptom duration before diagnosis of PA was 7 months. Clinical features of the clonazepam-trial group (n=11) and the reassurance group (n=10) were non-significantly different. Response(+) was achieved by 2 patients (18.2%) in the clonazepam-trial group and by no patient in the reassurance group. Remission(+) was achieved by 6 patients (54.5%) in the clonazepam-trial group and by one patient (10%) in the reassurance group (p=0.040). CONCLUSION: When PA children with MR with severe bowel distention are considered for surgical treatment to prevent acute abdomen, a trial of clonazepam could be recommended.

Clonazepam induced maculopapular rash: a case report.

Clonazepam is a benzodiazepine with prominent anticonvulsant action than other members of the group at equisedating doses. It especially blocks pentylenetetrazole-induced seizures. Other important actions include anxiolysis. Common adverse effects to Clonazepam include drowsiness and lethargy. In this submission we report a case of Clonazepam induced maculopapular rash in a 30 year old female treated for panic disorder.

Video-electroencephalogram monitoring in children with nonconvulsive status epilepticus / 中华实用儿科临床杂志

Objective To explore the clinical features and video-electroencephalogram (VEEG) monitoring of nonconvulsive status epilepticus (NCSE) in children.Methods 1.Object of study:Seventeen patients of NCSE diagnosed with Kaplan's criteria were analyzed in Children's Hospital of Fudan University between Oct.2009 and Sep.2012.2.Data analysis:Data on demographics,etiology,clinical manifestation and response to clonazepam therapy were analyzed.3.Therapies:Clonazepam 0.05 mg/kg was intravenously injected twice a day.Treatment of poor efficacy patients was combined with other antiepileptic drugs.4.Therapeutic effect:Clinical assessment of cognitive improvement and VEEG monitoring of background activity or paroxysmal abnormalities were analyzed.Results Nine male and 8 female of 17 patients with NCSE were involved,from 11 months to ll.4-year old.The clinical attacks lasted ranging variously time from 4 hours to 3 months.Each patient had a prolonged change of consciousness,accompanied by psychological or behavioral changes.Definite medical causes were identified in 65％ (11/17 cases) of the patients.Secondary epilepsy was the dominating cause.The characteristics of ictal VEEG in NCSE generally included slow activity and focal or generalized δ or θ activity.After clonazepam treatment,the conditions of 13 patients were under complete control,in which 4 had improvement.Six cases of unknown cause were fully controlled within 72 hours after intravenous injection of clonazepam.The prognosis of CNS infection sequelae patients,metabolism disorders and brain structural damage was poor.Conclusions NCSE may present with confusion,behavioral disturbances and psychiatric conditions.The diagnosis can be made by the ictal and interictal VEEG monitoring.It is necessary to make the diagnosis and control the seizures as quickly as possible.Clonazepam is useful in NCSE.

Development and validation of an RP-HPLC method for the simultaneous determination of Escitalopram Oxalate and Clonazepam in bulk and its pharmaceutical formulations.

A Simple, efficient and reproducible reverse phase high performance liquid chromatographic method was developed and validated for the Simultaneous determination of Escitalopram oxalate and Clonazepam in combined dosage form. The separation was effected on a Hypersil ODS C18 column (250mm X 4.6mm; 5μ) using a mobile phase mixture of buffer and acetonitrile in a ratio of 50:50 v/v at a flow rate of 1.0ml/min. The detection was made at 240nm. The retention time of Escitalopram oxalate and Clonazepam was found to be 2.840± 0.007min and 4.007±0.006 min. Calibration curve was linear over the concentration range of 20-120μg/ml and 1-6μg/ml for Escitalopram oxalate and Clonazepam. All the analytical validation parameters were determined and found in the limit as per ICH guidelines, which indicates the validity of the method. The developed method is also found to be precise, accurate, specific, robust and rapid for the simultaneous determination of Escitalopram oxalate and Clonazepam in tablet dosage forms.