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Objective: We compare the effect of HAS, a-tDCS on the left dorsolateral prefrontal cortex (l-DLPFC), and rest-testing on pain measures [(cold pressor test (CPT) (primary outcome) and heat pain threshold]. We also compare their effects on the motor evoked potential (MEP) (primary outcome), short intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP). Methods: This randomized, blind, crossover trial included 18 women with fibromyalgia, aged from 18 to 65 years old. They received at random and in a crossover order a-tDCS over the l-DLPFC (2mA), HAS, or a rest-testing. Results: HAS compared to a-tDCS increased the pain tolerance with a moderate effect size (ES) [Cohen's f=-0.78; (CI 95%; -1.48 to -0.12)]. While compared to rest-testing, HAS increased the CPT with a large ES [Cohen's f=-0.87; (CI 95%; -1.84 to -0.09)]. The a-tDCS compared to HAS increased the MEP amplitude with large ES [Cohen's f=-1.73 (CI 95%; -2.17 to -0.17)]. Likewise, its ES compared to rest-testing in the MEP size was large [Cohen's f=-1.03; (CI 95%; -2.06 to -0.08)]. Conclusion: These findings revealed that HAS affects contra-regulating mechanisms involved in perception and pain tolerance, while the a-tDCS increased the excitability of the corticospinal pathways. They give a subsidy to investigate their effect as approaches to counter regulate the maladaptive neuroplasticity involved in fibromyalgia. Clinical Trial Registration: www.ClinicalTrials.gov, identifier - NCT05066568.
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Oil in water nano-emulsions are drug delivery systems constituted by liquid lipophilic nano-droplets dispersed through the external aqueous phase, often reaching the kinetic stability with surfactant as stabilizers. Essential oils can be the oily phase or the source of bioactive compounds. In this study, the essential oil of Aeollanthus suaveolens-a plant used in folk medicine due to its psychopharmacological effects-was used for preparation of fine nano-emulsions by a low-energy titrating method. Monodisperse small nano-droplets (ca. 70 nm; PdI 0.200) were assembled by using blends of non-ionic surfactants, indicating modulation on surfactant system lead to altering the physical property. In a separate set of experiments, we investigated the role of this modulation on biological properties of the optimal nano-emulsion. The zebrafish embryos were more susceptible to the nano-emulsion than the bulk essential oil, showing the improved bioactivity due to nano-sizing. Therefore, adult zebrafish was treated, and paralysis was observed in the groups treated with the nano-emulsion, being this finding in accordance with hypnosis. At the same essential oil dose, another behavior was observed, suggesting that expected dose-dependent effects associated to sedative-hypnotics can be achieved by nano-sizing of psychoactive essential oils. This paper contributes to the state-of-art drug delivery systems by opening perspectives for novel sedative-hypnotics nano-emulsified essentials oils that can reach hypnotic effects at considerably lower dose, when compared with bulk materials, being useful for further completed dose-response studies.Graphical abstract.
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Lamiaceae/química , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Animais , Emulsões , Nanotecnologia , Óleos Voláteis/química , Óleos de Plantas/química , Tensoativos , Água , Peixe-ZebraRESUMO
OBJECTIVE: We evaluated whether active(a)-tDCS combined with hypnotic analgesia suggestion (HS) would be more effective than a single active(a)-tDCS, and/or sham-(s)-tDCS and s-tDCS/HS on the following outcomes: function of descending pain modulatory system (DPMS) during the conditioned pain modulation test (CPM-test) (primary outcome), heat pain threshold (HPT), heat pain tolerance (HPTo) and cold pressor test (CPT) (secondary outcomes). We also examined whether their effects are related to neuroplasticity state evaluated by serum brain-derived-neurotropic factor (BDNF). MATERIALS AND METHODS: Forty-eight females received one session of one of the four interventions (a-tDCS/HS, s-tDCS/HS, a-tDCS, and s-tDCS) in an incomplete randomized crossover sequence. The a-tDCS or s-tDCS was applied over the left dorsolateral prefrontal cortex (DLPFC) for 30 minutes at 2mA. RESULTS: A generalized linear model revealed a significant main effect for the intervention group (P <0.032). The delta-(Δ) pain score on the Numerical Pain Scale (NPS0-10) during CPM-test in the a-tDCS/HS group was -0.25 (0.43). The (Δ) pain score on NPS (0-10) during CPM-test in the other three groups was a-tDCS=-0.54 (0.41), HS -0.01 (0.41) and s-tDCS/HS=-0.19 (0.43). A-tDCS/HS intervention increased the CPT substantially compared to all other interventions. Also, higher baseline levels of BDNF were associated with a larger change in CPT and HPTo. CONCLUSION: These findings indicate that the HS combined with a-tDCS mitigated the effect of the a-tDCS on the DPMS. The a-tDCS up-regulates the inhibition on DPMS, and the HS improved pain tolerance. And, together they enhanced the reaction time substantially upon the CPT. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT03744897.
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Midazolam (MID) is a sedative drug which can be added in beverage samples as drug-facilitated-sexual assault (date rape drug). This type of drug has short half-life in biological fluids (not detectable) which often prevents the correlation between drug abuse and crime. In this work, we described a simple and low-cost method for fast screening and selective determination of MID in beverage samples (vodka, whiskey and red wine). For the first time, the electrochemical oxidation of MID was used for this purpose. The oxidation mechanism was studied using electrochemical techniques (cyclic and square-wave voltammetry) and computational simulations (density functional theory calculations). Differential-pulse voltammetry, boron-doped diamond electrode (BDDE), and Britton-Robinson (BR) buffer (pHâ¯=â¯2) were selected as electrochemical analysis technique, working electrode and supporting electrolyte, respectively. Different linear response ranges (4-25⯵molâ¯L-1 with râ¯=â¯0.9972; 1-10⯵molâ¯L-1 with râ¯=â¯0.9951; 1-15⯵molâ¯L-1 with râ¯=â¯0.9982) and limits of detection (0.46, 0.43 and 0.33⯵molâ¯L-1) were obtained for the analysis of vodka, whisky, and red wine solutions, respectively. The precision and accuracy were satisfactory considering the low relative standard deviation values (RSDâ¯<â¯6.3%, nâ¯=â¯15) and minimal sample matrix effects (recovery values between 87 and 103%).
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The aim of this study was to characterize the central effects of the Hyptis martiusii leaf essential oil (OEHM) and 1,8-cineole (eucalyptol) using behavioral animal models. Gas chromatography coupled to mass spectrometry (GC/MS) was used to characterize the chemical compounds present in the OEHM. For the behavioral tests, female Swiss mice treated with the OEHM (25, 50, 100 and 200â¯mg/kg, i.p.) and 1,8-cineole (50â¯mg/kg, i.p.) were used and subjected to the following tests: open field, elevated cross maze, rotarod, sodium pentobarbital- or ethyl ether-induced sleep time, pentylenetetrazol-induced convulsions, haloperidol-induced catalepsy, and ketamine-induced hyperkinesia. GC/MS analysis identified 20 constituents with the majority of them being monoterpenes and sesquiterpenes, with eucalyptol (1,8-cineol), the major sample compound (25.93%), standing out. The results showed the OEHM (25, 50â¯100 and 200â¯mg/kg, i.p.) and its major compound (50â¯mg/kg, i.p.) reduced animal motility in the open field test, increased pentobarbital- and ethyl ether-induced sleep time, as well as death latency in the pentylenetetrazole-induced convulsion model. However, the tested compounds were devoid of anxiolytic-like and myorelaxant activity. In addition, the OEHM (100 and 200â¯mg/kg, i.p.) and 1,8-cineole (50â¯mg/kg, i.p.) potentiated haloperidol-induced catalepsy and reduced ketamine-induced hyperkinesia. Taken together, the results suggest the OEHM has important hypnotic-sedative and antipsychotic-like effects, which appear to be due to the monoterpene 1,8-cineole, the major compound identified in the essential oil.
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Sistema Nervoso Central/efeitos dos fármacos , Eucaliptol/farmacologia , Hyptis/química , Óleos Voláteis/farmacologia , Animais , Eucaliptol/toxicidade , Feminino , Hipercinese/tratamento farmacológico , Ketamina , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Atividade Motora/efeitos dos fármacos , Óleos Voláteis/toxicidade , Folhas de Planta/química , Sono/efeitos dos fármacosRESUMO
Objectives: This paper aims to determine if hypnotic analgesia suggestion and transcranial direct-current stimulation (tDCS) have a differential effect on pain perception. We hypothesized that transcranial direct-current stimulation would be more effective than hypnotic analgesia suggestion at changing the descending pain modulating system, whereas the hypnotic suggestion would have a greater effect in quantitative sensory testing. Design: This is a randomized, double blind and crossover trial. Settings: All stages of this clinical trial were performed at the Laboratory of Pain and Neuromodulation of the Hospital de Clínicas de Porto Alegre. Subjects: Were included 24 healthy females aged from 18 to 45 years old, with a high susceptibility to hypnosis, according to the Waterloo-Stanford Group Scale of Hypnotic Susceptibility, Form C (15). Methods: The subjects received a random and crossover transcranial direct-current stimulation over the dorsolateral prefrontal cortex (2 mA for 20 min) and hypnotic analgesia (20 min). Results: Only hypnotic suggestion produced changes that are statistically significant from pre- to post-intervention in the following outcomes measures: heat pain threshold, heat pain tolerance, cold pressure test, and serum brain-derivate-neurotrophic-factor. The analysis showed a significant main effect for treatment (F = 4.32; P = 0.04) when we compared the delta-(Δ) of conditioned pain modulation task between the transcranial direct-current stimulation and hypnotic suggestion groups. Also, the change in the brain-derivate-neurotrophic-factor was positively correlated with the conditioned pain modulation task. Conclusion: The results confirm a differential effect between hypnotic suggestion and transcranial direct-current stimulation on the pain measures. They suggest that the impact of the interventions has differential neural mechanisms, since the hypnotic suggestion improved pain perception, whereas the transcranial direct-current stimulation increased inhibition of the descending pain modulating system. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03744897. Perspective: These findings highlight the effect of hypnotic suggestion on contra-regulating mechanisms involved in pain perception, while the transcranial direct-current stimulation increased inhibition of the descending pain modulating system. They could help clinicians comprehend the mechanisms involved in hypnotic analgesia and transcranial direct-current stimulation and thus may contribute to pain and disability management.
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Resumen Introducción: La hipnosis anestésica puede ser un recurso útil para procedimientos dolorosos. Desarrollo: Se reporta caso de una joven que requiere exodoncia de terceros molares, con uso de hipnosis como único anestésico. El proceso de enfermería inicia con la valoración según patrones funcionales, impresiona lo sana que se encuentra, sin antecedentes mórbidos relevantes ni contraindicación para anestesia química. Se selecciona diagnóstico NANDA de Disposición para mejorar el confort. Dentro del plan se incorporan el NIC 5920 Hipnosis y 5922 Facilitar la autohipnosis, con buena evolución según lo planificado. Resultados: La extracción con hipnosis anestésica se desarrolló de forma similar a la cirugía con anestesia química, la cual se realizó sin dolor. En posoperatorio, paciente practica autohipnosis, sin necesitar analgésicos y evolucionó favorablemente. Discusión: La hipnosis requiere mayor evidencia científica, pero su uso es prometedor. Se constataron los beneficios de la hipnosis en el abordaje del dolor. Conclusión: La hipnosis anestésica, fue útil como intervención de enfermería en cirugía dental. La autohipnosis contribuyó al buen resultado. El profesional de Enfermería entrenado en hipnosis está en condiciones de incorporarla en la gestión del cuidado. El caso resulta interesante, dado que la paciente opta por la hipnosis, sin contraindicación para anestesia química, ya que no se encontró otro reporte de hipnoanestesia inducida por profesional de Enfermería, como anestésico único. Anecdóticamente, durante la filmación del procedimiento, una periodista entra espontáneamente en trance, por lo que requiere intervención del profesional de Enfermería para salir de él.
Abstract Introduction: Anesthetic hypnosis can be a useful resource to address painful procedures. Development: The case is of a young female patient requiring third-molars exodontia who underwent it under anesthetic hypnosis. The nursing process began with the assessment according to functional patterns. The patient was found healthy and without relevant morbid antecedents nor drug-anesthesia contraindications. A comfort improving disposition NANDA diagnosis was selected. NIC 5922 and 5920 were incorporated to the intervention plan. Results: The extraction under anesthetic hypnosis was performed in a similar form in comparison to a drug-anesthesia extraction procedure. During the post operatory stage, the patient used self-hypnosis and responded favorably without analgesics. Discussion: While hypnosis requires more scientific evidence, its use appears to be promising. In this case, diverse benefits from using hypnosis to address a painful procedure were acknowledged. Conclusion: Anesthetic hypnosis proved being helpful in a dental-surgery related nursing intervention. Self-hypnosis also contributed to the favorable outcome. A nursing professional who is well trained in hypnosis can incorporate this kind of procedure into her care management approach. This particular case was interesting because the patient chose hypnosis over drug anesthesia, and no other report on a nursing staff induced anesthetic hypnosis was found. Anecdotally, during the filming of this procedure, a journalist suffered an emotional trance which required immediate nursing intervention.
Resumo Introdução: A hipnose anestésica pode ser um recurso útil para procedimentos dolorosos. Desenvolvimento: Informa-se o caso de uma garota que requer exodontia de terceiros molares, com uso de hipnoses como único anestésico. O processo de enfermagem inicia com a valoração segundo padrões funcionais, impressiona o saudável que se encontra, sem antecedentes mórbidos relevantes nem contraindicação para anestesia química. Seleciona-se diagnóstico NANDA de Disposição para melhorar o conforto. Dentro do plano se incorporam o NIC 5920 Hipnose e 5922 Facilitar a auto-hipnose, com boa evolução segundo o planejado. Resultados: A extração com hipnose anestésica desenvolveu-se de forma similar à cirurgia com anestesia química, a qual se realizou sem dor. Em pós-operatório, o paciente prática auto-hipnose, sem precisar analgésicos e evolucionou favoravelmente. Discussão: A hipnose requer maior evidencia científica, mas seu uso é promissor. Verificaram os benefícios da hipnose na abordagem da dor. Conclusão: A hipnose anestésica foi útil como intervenção de enfermagem em cirurgia dental. A auto-hipnose contribuiu para o bom resultado. O profissional de Enfermagem treinado em hipnose está em condições de incorporá-la na gestão do cuidado. O caso resulta interessante, dado que a paciente opta pela hipnose, sem contraindicação para anestesia química, já que não se encontrou outro relatório de hipnoanestesia induzida por profissional de Enfermagem, como anestésico único. Anedoticamente, durante a filmagem do procedimento, uma jornalista entrou espontaneamente em transe, pelo qual se requereu intervenção do profissional de Enfermagem para sair dele.
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STUDY OBJECTIVE: The use of benzodiazepines and the development of dementia is controversial, with studies indicating that benzodiazepines could be either a protective factor or a risk factor for dementia, or no association may exist between the two. Our objective was to identify whether such an association exists. DESIGN: Systematic review and meta-analysis of 12 prospective and retrospective cohort studies and case-control studies. PARTICIPANTS: A total of 981,133 (in the systematic review) and 980,860 (in the meta-analysis) adults or elderly individuals. MEASUREMENTS AND MAIN RESULTS: A search of the PubMed, LILACS, and Cochrane Central Register of Controlled Trials databases, as well as a manual search of the reference lists of the included publications and reviews, was performed. We included studies that reported the incidence of dementia and in ever users of benzodiazepines. Data were analyzed by using a random effects model in R software. Quality of the evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) certainty ratings system. The results of the main meta-analysis suggest that benzodiazepines can be a risk factor for developing dementia (odds ratio 1.38, 95% confidence interval 1.07-1.77; I2 = 98%; 95% prediction interval 0.58-3.25; very low certainty). CONCLUSION: Our results suggest an association between the use of benzodiazepines and the development of dementia. However, the current evidence lacks the power to infer differences between the effects of Alzheimer's disease and vascular dementias, long-acting and short-acting benzodiazepines, and various exposure loads (duration and dose). Future long-term prospective cohort studies are necessary, with adequate adjustments for confounding variables, strategies to minimize reverse causality, reporting of subgroups aimed at greater homogeneity of findings, adequate statistical power to identify high-magnitude effects, and defined daily dose analyses for dose-response gradient.
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Doença de Alzheimer/etiologia , Benzodiazepinas/administração & dosagem , Demência/etiologia , Adulto , Idoso , Doença de Alzheimer/epidemiologia , Benzodiazepinas/efeitos adversos , Demência/epidemiologia , Relação Dose-Resposta a Droga , Humanos , Projetos de Pesquisa , Fatores de RiscoRESUMO
Species of the genus Tabebuia are used in traditional medicine and are reported in the literature for their properties against various diseases. The objective of this study was to evaluate the antipyretic, sedative and hypnotic activities of methanol extract of Tabebuia hypoleuca stems (THME) using the Brewer's yeast induced pyrexia, Open field and Sodium thiopental-induced sleeping time tests, respectively. In the Brewer's yeast induced pyrexia test, THME at 500 mg/kg produced a significant (p<0.001) decrease of the fever as from the first hour after administration and was sustained for 4 h. In the Open-field test, THME did not cause any significant change in the number of crossings, rearing, preening and defecation, and either in the time of immobility. Moreover, THME did not produce changes in neither the sleeping latency nor the sleeping time induced by sodium thiopental. These results showed that THME administered orally at 500 mg/kg exerts antipyretic activity, probably mediated by the inhibition of the enzyme cyclooxygenase-2. This study also showed that THME does not exert sedative and hypnotic effects at the doses tested.
Especies del geÌnero Tabebuia se utilizan en la medicina tradicional y se reportan en la literatura por sus propiedades contra diversas enfermedades. El objetivo de este estudio fue evaluar la actividad antipireÌtica, sedante e hipnoÌtica del extracto metanoÌlico de los tallos de Tabebuia hypoleuca (THME) utilizando las pruebas de pirexia inducida por levadura de cerveza, campo abierto y tiempo de suenÌo inducido por tiopental soÌdico respectivamente. En el ensayo de pirexia inducida por levadura de cerveza, THME a 500 mg/kg produjo una reduccioÌn significativa (p<0.001) de la fiebre a partir de la primera hora despueÌs de la administracioÌn y se mantuvo durante cuatro horas. En el ensayo de campo abierto, THME no causoÌ ninguÌn cambio significativo en el nuÌmero de cruces, levantamientos, acicalamientos y defecacioÌn, ni en el tiempo de inmovilidad. AdemaÌs, THME no produjo cambios ni en la latencia de suenÌo, ni en el tiempo de suenÌo inducido por tiopental soÌdico. Estos resultados mostraron que THME administrado oralmente en dosis de 500 mg/kg posee actividad antipireÌtica, mediado probablemente a la inhibicioÌn de la enzima ciclooxigenasa-2. Este estudio tambieÌn demostroÌ que THME no posee actividad sedante e hipnoÌtica en las dosis ensayadas.
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Animais , Masculino , Ratos , Antipiréticos/farmacologia , Hipnóticos e Sedativos/farmacologia , Extratos Vegetais/farmacologia , Tabebuia/química , Metanol , Ratos Sprague-DawleyRESUMO
RESUMO O presente trabalho busca promover uma aproximação teórica entre a inconicidade, capacidade dos signos de transmitirem qualidades de um objeto, e uma perspectiva complexa da comunicação hipnótica. Essa discussão é desenvolvida em torno de três tópicos principais. O primeiro é a heterogeneidade semiótica dos processos comunicacionais da hipnose; o segundo consiste numa articulação entre o individual e o coletivo; e o terceiro, nas relações entre a noção de ethos e sentimento. O trabalho é concluído destacando que, malgrado as dificuldades conceituais, as relações entre iconicidade e complexidade proporcionam grandes contribuições no que diz respeito a temas importantes da comunicação hipnótica, como a subjetividade, a experiência do terapeuta, a pesquisa e o pertencimento.
ABSTRACT The present paper proposes a theoretical approximation between iconicity, which is the signs’ ability to transmit the resemblance with objects, and a complex perspective of hypnotic communication. The discussion is developed based on three main topics. The first is that of semiotic heterogeneity of communicative processes of hypnosis; the second consists of an articulation between the individual and the collective; and third, in the relation between the notions of ethos and sentiment. The paper concludes that in spite of conceptual difficulties the relationship between iconicity and complexity propitiate great contributions regarding important themes in hypnotic communication, such as subjectivity, the therapist’s experience, research, and belonging.
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Santiago Ramón y Cajal (1852-1934) did not only contribute to neurobiology and neurohistology. At the end of the 19th century, he published one of the first clinical reports on the employment of hypnotic suggestion to induce analgesia (hypnoanalgesia) in order to relieve pain in childbirth. Today, the clinical application of hypnoanalgesia is considered an effective technique for the treatment of pain in medicine, dentistry, and psychology. However, the knowledge we have today on the neural and cognitive underpinnings of hypnotic suggestion has increased dramatically since Cajal's times. Here we review the main contributions of Cajal to hypnoanalgesia and the current knowledge we have about hypnoanalgesia from neural and cognitive perspectives.
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OBJECTIVES: We aimed to describe a group of adults diagnosed with sleep-related eating disorder (SRED) at the Sleep Medicine Center of the Pontificia Universidad Catolica de Chile. METHODS: We performed a descriptive study of 34 consecutive patients who met the criteria of the International Classification of Sleep Disorders for SRED evaluated during a 3-year period who did not have an eating disorder according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. All patients had a structured clinical interview performed by a sleep specialist and completed the Beck Depression Inventory (BDI). Polysomnography (PSG) was performed when clinically indicated for ruling out other sleep-related disorders (18 patients; 52.9%). Patients' demographic and clinical data, comorbidities, and treatment response also were analyzed. RESULTS: Most patients were women (n=23; 67.6%). The average age at the time of diagnosis was 39±13.8 (17-67 years) and the latency since symptom onset was 8.3±8.8 years. Most patients had several episodes per night (average, 2.6±1.6; 1-8) and all except one patient had partial or total amnesia of these events (n=33; 97%). Comorbidities were frequent and included insomnia (n=20; 58.8%), restless legs syndrome (RLS) (n=16; 47%), sleep-disordered breathing (SDB) (n=9; 26%), psychiatric disorders (n=13; 38.2%), and overweight or obesity (n=14; 41.1%). Most patients were hypnotic users (n=21; 61.7%) and reported weight-centered anxiety (n=23; 67.6%). Twenty patients (58.8%) were treated with topiramate, 17 of whom had adequate symptomatic responses. CONCLUSION: Our SRED patients showed female preponderance, amnesia during the episodes, association with other sleep disorders, use of hypnotics, weight-centered anxiety, and positive response to topiramate. The presence of anxiety focused on weight in most patients may be an important element in the emergence of this behavior during sleep.
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Transtornos da Alimentação e da Ingestão de Alimentos/complicações , Transtornos do Sono-Vigília/complicações , Adolescente , Adulto , Idoso , Chile/epidemiologia , Comorbidade , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , Transtornos da Alimentação e da Ingestão de Alimentos/tratamento farmacológico , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Feminino , Frutose/análogos & derivados , Frutose/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/uso terapêutico , Polissonografia , Síndrome das Pernas Inquietas/epidemiologia , Fatores Sexuais , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/epidemiologia , Topiramato , Adulto JovemRESUMO
Eszopiclone is the S-isomer of racemic zopiclone, a cyclopyrrolone with sedative-hypnotic activity that has been available in Europe, Canada, and Latin America since 1987. Eszopiclone acts by binding to the GABA(A) receptor. In contrast to the benzodiazepine (BZD) hypnotics, eszopiclone has more selectivity for certain subunits of the GABA(A) receptor. Oral eszopiclone is rapidly absorbed and extensively distributed to body tissues including the brain. Peak plasma concentrations are attained 1.0-1.6 hours after a 3 mg dose, while the mean elimination half-life is 6 hours. The half-life increases with age to about 9.0 hours in patients 65 years or older. Eszopiclone's pharmacokinetic (PK) profile is not substantially modified in patients suffering from renal failure or mild-to-moderate hepatic impairment, although patients with severe hepatic insufficiency should have a reduced dose. The subjective perception of improved sleep following eszopiclone 2 or 3 mg treatment has been demonstrated in randomized, double-blind, placebo-controlled studies of up to 6 months' duration. In these studies the drug significantly reduced sleep onset latency (SOL), the number of awakenings, and wake time after sleep onset (WASO) whereas total sleep time (TST) and quality of sleep were increased in non-elderly and elderly subjects. Sleep laboratory studies of the effects of eszopiclone have confirmed the drug's clinical efficacy in subjects with chronic primary insomnia. Eszopiclone, unlike BZD hypnotics, does not significantly alter values corresponding to slow wave sleep (SWS or stages 3 and 4) and rapid eye movement (REM) sleep. Rebound insomnia following withdrawal of eszopiclone has been examined in only one study. Discontinuation of the active treatment with 2 mg was followed by rebound insomnia in non-elderly subjects. Three-mg doses of eszopiclone administered for a period of up to 12 months was associated with a sustained beneficial effect on sleep induction and maintenance, with no occurrence of tolerance. The most common side-effects were unpleasant or bitter taste, headache, dyspepsia, pain, diarrhea, dry mouth, upper respiratory infection, urinary tract infection, dizziness, and accidental injury. New adverse events (withdrawal symptoms) including anxiety, abnormal dreams, hyperesthesia, nausea, and upset stomach were recorded in one study on the days following eszopiclone 2 or 3 mg discontinuation. Although dependence and abuse potential have not been formally assessed, unpublished data show that eszopiclone at doses of 6 and 12 mg produces euphoria effects similar to those of diazepam 20 mg in BZD drug addicts. In conclusion, available evidence tends to indicate that eszopiclone is effective and safe for the treatment of chronic primary insomnia in non-elderly and elderly subjects. Tolerance did not occur during active drug administration for a 12-month period. Thus eszopiclone can be efficacious not only during short- and intermediate-term administration but also in patients requiring prolonged regular drug usage.
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La presente revisión tiene por objetivo reunir evidencia de cambios neuroplásticos en dolor crónico y de procesos corticales y subcorticales implicados en la analgesia hipnótica. Se discuten las principales conclusiones para intervenciones futuras.
The objective of the present review is to gather evidence of neuroplasticity changes in chronic pain and cortical and subcortical processes implied in hypnotic analgesia. The main conclusions are discussed for future interventions.