Association of low-dose naltrexone and transcranial direct current stimulation in fibromyalgia: a randomized, double-blinded, parallel clinical trial

Abstract Introduction Fibromyalgia is a complex, generalized, and diffuse chronic musculoskeletal pain. Pharmacological approaches are widely used to relieve pain and increase quality of life. Low-Dose Naltrexone (LDN) was shown to increase the nociceptive threshold in patients with fibromyalgia. Transcranial Direct Current Stimulation (tDCS) is effective for pain management. Objective The purpose of this study was to evaluate the analgesic and neuromodulatory effects of a combination of LDN and tDCS in patients with fibromyalgia. Methods This was a randomized, double-blinded, parallel, placebo/sham-controlled trial (NCT04502251; RBR-7HK8N) in which 86 women with fibromyalgia were included, and written informed consent was obtained from them. The patients were allocated into four groups: LDN + tDCS (n = 21), LDN + tDCS Sham (n = 22), placebo + tDCS (n = 22), and placebo+tDCS Sham (n = 21). The LDN or placebo (p.o.) intervention lasted 26 days; in the last five sessions, tDCS was applied (sham or active, 20 min, 2 mA). The following categories were assessed: sociodemographic, Visual Analog Pain Scale (VAS), Pain Catastrophizing Scale (PCS), State-Trait Anxiety Inventory (STAI), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI-II), Profile of Chronic Pain Scale (PCP:S), Pain Pressure Threshold (PPT), and Conditioned Pain Modulation (CPM). Blood samples were collected to analyze BDNF serum levels. Results At baseline, no significant difference was found regarding all measurements. VAS pain was significantly reduced in the LDN + tDCS (p = 0.010), LDN + tDCS Sham (p= 0.001), and placebo+tDCS Sham (p= 0.009) groups. In the PCP:S, the LDN+tDCS group showed reduced pain frequency and intensity (p= 0.001), effect of pain on activities (p= 0.014) and emotions (p= 0.008). Depressive symptoms reduced after all active interventions (p > 0.001). Conclusion Combined LDN+tDCS has possible benefits in reducing pain frequency and intensity; however, a placebo effect was observed in pain using VAS, and further studies should be performed to analyze the possible association.

NALTREXONE AS A TREATMENT FOR HEROIN DEPENDENCE AND ITS RELATIONSHIP WITH DEPRESSION

BACKGROUND- our study was aimed to know does Naltrexone used in opioid-dependent patient has any relation with the onset of depression. METHOD- Naltrexone was given to 30 opioid-dependent patients who had undergone inpatient detoxification with no underlying psychiatric comorbidity at baseline. HAM-D was applied at 2,4,6 weeks post Naltrexone initiation. RESULTS: Our study showed that at 2 weeks, 60% of patients showed depressive symptoms out of which 37% met the criteria for mild depressive disorder and 23% met the criteria for moderate to severe depression. At 4 and 6 weeks, majority continued to be depressive while only 3% of the patients showed improvement in depressive features. CONCLUSION: From our study, we concluded that a positive correlation was found between Naltrexone and Depression in Opioid users

Effects of topiramate, bupropion and naltrexone isolated or combined on subcutaneous adipose tissue in obese rats

ABSTRACT Objective: To evaluate the effects of combining topiramate, bupropion and naltrexone in obesity-induced rats on their weight and subcutaneous adipose tissue. Methods: A total of 40 male Wistar rats were induced to obesity for 8 weeks and the animals were divided into 8 groups: Ctr - control, G0 - Sham, G1 - oral saline solution (1.0mL/day), G2 - topiramate (20.0mg/kg) and bupropion (5.0mg/kg), G3 - naltrexone (20.0mg/kg), G4 - topiramate (20.0mg/kg), G5 - bupropion (5.0mg/kg) and G6 - topiramate (20.0mg/kg), bupropion (5.0mg/kg) and naltrexone (20.0mg/kg). During the experiment, all animals were weighed weekly. After 30 days of treatment animals were euthanized and their skin fragments were processed and stained with hematoxylin and eosin for morphological, morphometric and biochemical analyzes. Results: The only group that presented a decrease in the volume of subcutaneous adipose tissue was G3, but this decrease was not significant when compared with the other groups. The G4, the G5 and the G6 presented increased adipose tissue volume. Data showed that until the eighth week all animals increased their weight by approximately 50%. After treatment animals of all groups, except G3, increased their weight from 4% to 9% approximately. The G3 was the only group that lost weight, but this decrease was not significant. Conclusion: The medicines studied were not efficient in reducing weight in obese rats. However, it should be considered that 30-day treatment period is not enough to observe the stronger effects of these drugs.

Research progress on naltrexone in the treatment of children with inflammatory bowel disease / 中国小儿急救医学

Inflammatory bowel disease refers to a group of non-specific chronic gastrointestinal inflammatory diseases of unknown causes, including ulcerative colitis, Crohn′s disease and indeterminate colitis.Recently, the incidence of inflammatory bowel disease in children has increased, which seriously affects the growth and development of children and the quality of life.Studies have shown that the opioid receptor antagonist naltrexone can reverse the inflammatory activity in inflammatory bowel disease and promote cell repair.This review summarized the research of application of naltrexone in the treatment of inflammatory bowel disease, aiming to further explore the effectiveness and safety of naltrexone in the treatment of inflammatory bowel disease in children.

Effects of naltrexone hydrochloride combined with trazodone on preventing relapse in heroin addicts after detoxification / 中国基层医药

Objective:To investigate the effects of naltrexone hydrochloride combined with trazodone on preventing relapse in heroin addicts after detoxification.Methods:A total of 274 opioid heroin addicts who received treatment in Beijing Gaoxin Hospital between June 2016 and January 2019 were included in this study. After detoxification with methadone, all patients were randomly assigned to receive either naltrexone hydrochloride combined with trazodone (group 1, n = 60) or naltrexone hydrochloride alone (group 2, n = 60) for preventing relapse in heroin addicts. The effects on relapse prevention were determined in each group. Results:There were no significant differences in age distribution, sex composition, marital status, and drug use between groups 1 and 2 (all P > 0.05). After 6 months of treatment, the non-relapse rate was 86.7% (52/60) and 6.7% (4/60) in groups 1 and 2 respectively, in the case of unchanged personal life status. There was significant difference in non-relapse rate between groups 1 and 2 ( χ2 = 77.1, P < 0.001). Conclusion:Naltrexone hydrochloride combined with trazodone exhibits superior efficacy in preventing relapse in opioid heroin addicts after detoxification to naltrexone hydrochloride alone.

Understanding the Mechanism of Action and Clinical Implications of Anti-Obesity Drugs Recently Approved in Korea / 가정의학회지

The Korean Ministry of Food and Drug Safety has approved three anti-obesity drugs for long-term management in the past decade. In addition, since 2019, bariatric surgery has been financially supported by National Health Insurance Service in Korea. In this review, the mechanisms of action and the clinical implications of the recently approved anti-obesity drugs, lorcaserin, naltrexone/bupropion, and liraglutide are explained. Lorcaserin stimulates proopiomelanocortin (POMC)/cocaine- and amphetamine-regulated transcript (CART) neurons and inhibits neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons, which results in the activation of melanocortin 3/4 receptors. Naltrexone/bupropion stimulates POMC neurons through bupropion; this stimulation is augmented by blocking the autoinhibitory mechanism of POMC with naltrexone. The hypophagic effect of liraglutide is mediated through the direct activation of POMC/CART neurons and the indirect suppression of NPY/AgRP neurons through γ-aminobutyric acid-dependent signaling, with adjunctive suppression of the mesolimbic dopamine reward system. In addition to liraglutide, another glucagon-like peptide-1 receptor agonist, semaglutide, is expected to be added to the list of anti-obesity drugs in the near future. In patients with obesity and high cardiovascular risk, lorcaserin was considered neutral and liraglutide was considered favorable, whereas inconclusive results were obtained for naltrexone/bupropion.

Neurobiological Basis of Craving and Anti-Craving Medications / 신경정신의학

Clinical studies published over the past two decades have consistently demonstrated the therapeutic efficacy and safety of anti-craving medications. To use anti-craving agents more effectively in clinical settings, it is important to set clear treatment goals. Because alcoholic patients have lost control of drinking alcohol, it is recommended to set ‘abstinence’ as a goal rather than ‘controlled drinking’. Indeed, the therapeutic effects of anti-craving medication are higher when abstinence is set as the target. On the other hand, if abstinence is the sole criterion, it is difficult to elicit the motivation of a patient who lacks motivation in clinical practice. In the case of patients who have not yet gained insight, the initial goal might be set to gradually reduce the amount of alcohol consumed and prevent at-risk heavy drinking. Even in this case, anti-craving can help clinically. To increase the effectiveness of anti-craving medications, it is best to start at least four to seven days after the patient has stopped drinking. If the patient has alcohol withdrawal symptoms, they should be treated first.

Naltrexone-associated Visual Hallucinations: A Case Report

Naltrexone is a competitive antagonist of μ, δ, and κ opioid receptors. Naltrexone has been investigated for use an as anti-obesity agent in both the general population and in patients with severe mental illness, including schizophrenia. In patients with schizophrenia, however, potential psychotic symptoms due to adverse effects of naltrexone have not been investigated. Our case study, a relevant case report, and some related articles suggest that naltrexone might be associated with the emergence of visual hallucinations, which clinicians should be aware of.

Immuno-regulatory effects on murine macrophages by low dose naltrexone (LDW) / 中国免疫学杂志

Objective:The effect of naltrexone on function of murine peritoneal macrophage in vitro was studied in order to illuminate its immune activity futher. Methods:Peritoneal macrophages were divided in three groups:RPMI1640 blank control group, LPS positive control group and NTX treated group. Various phenotypic and functional indices were tested by MTS, flow cytometry technology,phagocytosis experiment and ELISA. Results: Compared with RPMI1640 group,at a LDN exhibits paradoxical properties;the expression of CD64 on surface increased while the expression of CD206 decreased in NTX group;the expression of tumour necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β)were increased. Conclusion:The results of experiment had proved that LDN could influence macrophage polarzation, regulate the inflamatory mediators production and affect the phagocytosis function of peritoneal macrophage.

Clinical Efficacy and Safety of Naltrexone Combination Therapy in Older Patients with Severe Pruritus

BACKGROUND: Severe pruritus is a challenging condition, and it is more difficult to deal with in older patients due to their limitations in taking oral medication because of underlying diseases, possible interaction with concurrent medications, and poor general condition. OBJECTIVE: We evaluated the efficacy and safety of naltrexone (Revia®), an opioid antagonist, in elderly patients with severe pruritus that was not easily controlled with conventional antipruritics. METHODS: Eighteen patients were enrolled, with a mean age of 73 years. They additionally received 50 mg of naltrexone per day for an average of 2 months. RESULTS: Using the visual analogue scale, 13 (72.2%) of 18 patients showed a "much improved" condition, reporting more than a 50% decrease in pruritus intensity. Sixteen (88.9%) showed symptomatic improvement, and only 2 (11.1%) had persistent pruritus. Five patients reported side effects including insomnia, fatigue, constipation, and anorexia. However, reactions were either limited to the first 2 weeks or well managed. CONCLUSION: Naltrexone could be an effective and safe alternative treatment option to control severe pruritus in older patients.

New Drugs for Obesity Treatment / 대한내과학회지

There have recently been many advances in obesity treatment, including lifestyle modifications and pharmacological and surgical treatments. Specifically, pharmacological strategies have improved significantly. However, the history of the development of medications aimed at weight loss is complicated. The Federal Drug Administration (FDA) withdrew anti-obesity drugs such as fenfluramine, dexfenfluramine, and phenylpropylamine due to their unwanted side effects. Moreover, sibutramine was voluntarily withdrawn from the market and a new drug, rimonabant, has been suspended in the middle of a clinical trial due to unacceptable side effects. The FDA has approved four new anti-obesity drugs in recent years. Lorcaserin is a selective 5-hydroxytryptamine receptor 2c (5-HT2c) agonist. The pharmacological mechanism of action of this drug is similar to fenfluramine and dexfenfluramine, but lorcaserin is specific for 5-HT2c, which are located almost exclusively in the central nervous system and are not found in heart valves. Three phase 3 clinical trials for lorcaserin have been published recently; weight reduction was successful and no side effects involving the heart were found. Furthermore, the FDA has also approved phentermine/topiramate controlled-release (PHEN/TPM CR), which is composed of a combination of immediate-release phentermine and controlled-release topiramate. Weight reduction achieved with PHEN/TPM CR was demonstrated to be better than all other anti-obesity drugs. Lastly, the combination therapy bupropion/naltrexone activates proopiomelanocortin neurons and inhibits opioid-mediated negative feedback by synergism. Similar to liraglutide, a long-acting analogue of the hormone glucagon-like peptide-1, this treatment showed significant weight loss and metabolic improvements. However, in addition to its efficacy, clinicians should consider its side effects before use.

Safety of Anti-Obesity Drugs Approved for Long-Term Use

Because of the widespread use of ant-obesity medications, bariatricians need to be aware not only of common adverse events but also uncommon serious events in the pharmacotherapy of obesity. Safety and tolerability must be considered in selecting the drug, titrating the dosage, and monitoring patients. In Korea, orlistat and lorcaserine are the two anti-obesity drugs that can be used for long-term treatment, and in the US, liraglutide, phentermine/topiramate, and naltrexone/bupropion have been recently approved. In general, all of these drugs have very good safety and tolerability profiles. Common adverse events of these drugs are well understood, and they can be coped with or prevented by adjusting the dosage properly. In addition, patients can recover from serious events by stopping the medication. However, there are other serious side effects that need to be monitored for. These include liver injury, acute kidney injury, and pancreatitis for orlistat; valvulopathy for lorcaserine; thyroid C-cell pathology and pancreatitis for liraglutide; metabolic acidosis, urolithiasis, acute angle closure glaucoma, and teratogenic effects for phentermine/topiramate; and severe nausea and heart disease for naltrexone/bupropion.

Effect of nalmefene on cerebral ischemia-reperfusion injury in rats / 中华麻醉学杂志

Objective To investigate the effect of nalmefene on the cerebral ischemia-reperfusion (I/R) injury in rats.Methods Forty-eight male Sprague-Dawley rats, aged 3-4 months, weighing 220260 g, were randomly allocated to control group (group C), sham operation group (group S), cerebral I/R group (group I/R), or nalmefene group (group N) using a random number table, with 12 rats in each group.Cerebral I/R was induced by occlusion of bilateral common carotid arteries for 20 min followed by reperfusion.Group C received no treatment.Group S underwent 20 min exposure of bilateral common carotid arteries and then received suture.In group N, nalmefene 0.1 mg/kg was injected intraperitoneally immediately after reperfusion.At 6, 24 and 72 h of reperfusion, venous blood samples were collected for determination of the concentrations of S-100β protein and neuron-specific enolase (NSE) in plasma by enzyme-linked immunosorbent assay.After the last blood sampling, the rats were sacrificed, and brains were removed for determination of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) contents in brain tissues by enzyme-linked immunosorbent assay.Results Compared with group C, the plasma S-100β protein and NSE concentrations at each time point of reperfusion, and TNF-α and IL-1βcontents in brain tissues were significantly increased in S and I/R groups (P＜0.01).Compared with group S, the plasma S-100β protein and NSE concentrations at each time point of reperfusion, and TNF-α and IL-1β contents in brain tissues were significantly increased in group I/R (P＜0.01).Compared with group I/R, the plasma S-100β protein and NSE concentrations at each time point of reperfusion, and TNF-α and IL-1β contents in brain tissues were significantly decreased in group N (P ＜ 0.01).Conclusion Nalmefene can mitigate cerebral I/R injury in rats.

A Case Report: Irbesartan and Naltrexone Treatment of Polydipsia in a Patient with Schizophrenia / 대한정신분열병학회지

Polydipsia in schizophrenic patients is not uncommon, but a frequently underdiagnosed condition. The etiology of polydipsia remains unclear, and its complications can be life-threatening, while often being difficult to manage it. We report a case of a successfully treated chronic schizophrenic patient with polydipsia. The patient was male, 47-year-old, suffering 27-years of residual schizophrenia who had been consuming more than 10 L of water per day, and is complicated by hyponatremia. He was treated with irbesarten 300 mg and naltrexone 50 mg in the setting of closed ward. He consumed less than 3.5 L of water per day and serum sodium levels seemed to be stable following discharge from the closed ward. We suggest that irbesartan and naltrexone may have beneficial effects for treating polydipsia, and future prospective and well-controlled studies are to be performed.

Difference of the Naltrexone's Effects in Social Drinkers by Spicy Food Preference

The purpose of this study was to investigate the differences in subjective acute effects of alcohol and naltrexone among those who prefer spicy food to varying degrees. Acute biphasic alcohol effects scale (BAES), visual analogue scale for craving (VAS-C), blood alcohol concentration (BAC) and food preference scale were measured in 26 men. Repeated measures ANOVA (2 preference groupsx4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in naltrexone condition (N+) (P<0.001), but not in non-naltrexone condition (N-). Furthermore, repeated measures ANOVA (2 drug groupsx4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in strong preference for spicy food (SP) (P<0.001), but not in lesser preference for spicy food (LP). The paired t-test revealed that significant suppression of the stimulative subscale of BAES was observed at 15 min (P<0.001) and 30 min (P<0.001) after drinking when N+ compared with N- in SP. For those who prefer spicy food, the stimulative effect of acute alcohol administration was suppressed by naltrexone. This result suggests that the effect of naltrexone may vary according to spicy food preference.

Do opioid receptors play a role in the pathogenesis of the inflammatory response in acute pancreatitis? / Os receptores opioides desempenham papel na patogênese da resposta inflamatória na pancreatite aguda?

PURPOSE: To investigate the effect of the opioid blocker naltrexone in the inflammatory response in acute pancreatitis (AP). METHODS: Acute pancreatitis was induced in anesthetized male Wistar rats by retrograde injection of 2.5% sodium taurocholate diluted in 0.5ml saline into the main pancreatic duct. Animals were randomized to the following experimental groups: Control Group (n=9): animals received an intraperitoneal injection of saline solution (0.5ml), 15 minutes before the induction of AP. Naltrexone Group (n=9): animals received an intraperitoneal injection of naltrexone 0.5ml (15 mg/kg), 15 minutes before induction of AP. Peritoneal levels of TNF-α and serum levels of IL-6 and amylase were determined The volume of the ascitic fluid was also evaluated. Myeloperoxidase (MPO) activities were analyzed in homogenates of pulmonary tissue. RESULTS: There were no significant differences in the ascitic fluid volume, nor in TNF-a and IL-6 levels in the naltrexone group compared to controls. Treatment with naltrexone did not affect the lung MPO activity compared to control group. CONCLUSIONS: The opioid receptors don't play an important role in the pathogenesis of the inflammatory response in acute pancreatitis. If opioids affect leukocytes inflammatory signaling, there are no major implications in the pathogenesis of acute pancreatitis.

OBJETIVO: Investigar o efeito do bloqueador opióide naltrexone na resposta inflamatória da pancreatite aguda. METODOS: Pancreatite aguda foi induzida em ratos machos Wistar, através de injeção retrógada de solução de taurocolato de sódio a 2,5% nos ductos pancreáticos. Os animais foram alocados em dois grupos: Grupo controle (n=9) animais receberam 0,5 ml de solução salina intra-peritonial 15 minutos antes da indução da pancreatite aguda e Grupo naltrexone (n=9) animais receberam naltrexone (15mg/kg de peso), em 0,5 ml de volume final por via intraperitoneal, 15 minutos antes da indução da pancreatite aguda. Foram avaliados o volume de ascite, os níveis séricos de amilase e IL-6, assim como TNF-α peritoneal e a atividade da mieloperoxidase (MPO) no tecido pulmonar. RESULTADOS: Não foram encontradas diferenças significantes nos parâmetros analisados entre o grupo que recebeu solução salina e o que recebeu naltrexone . CONCLUSÕES: Os receptores opióides não desempenham papel importante na resposta inflamatória sistêmica associada à pancreatite aguda. Se os opioides alteram a sinalização inflamatória nos leucócitos está ação não se reflete na patogênese da pancreatite aguda.

Eficacia de la naltrexona en el tratamiento de prurito severo / Effectiveness of naltrexone in the treatment of severe pruritus

Introducción. El prurito es una complicación frecuente de las patologías hepáticas, que puede llegar a ser de difícil manejo. El incremento en el tono opioide cerebral se ha postulado como mecanismo fisiopatológico causal del prurito. Es así como el antagonismo opioide causa mejoría y resolución sintomática en estos pacientes. Objetivo. Describir el manejo de prurito severo con antagonismo opioide en una paciente refractaria a manejo médico convencional, y hacer una revisión de la literatura. Metodología y resultados. Este es el caso de una paciente de 50 años de edad, con antecedente de hepatitis autoinmune, quien se presenta con historia de cinco años de prurito severo secundario a colestasis, manejada con antihistamínicos, esteroides, ácido ursodeoxicólico y colestiramina sin mejoría. Se decide manejo con antagonismo opioide; se inicia con naloxona infusión por 24 horas, con dosis ascendentes desde 0,002 mcg/ kg/min, hasta 0,2 mcg/kg/min, y posteriormente naltrexona, hasta dosis de 50 mg día. Se evalúo la respuesta terapéutica por medio de escala visual análoga (EVA). Desde el inicio de la infusión se obtiene disminución en la EVA hasta valores de 0/10 durante las primeras 24 horas, con mejoría clínica y sintomática.Conclusiones. En el enfoque de la paciente con prurito refractario debe considerarse el uso de antagonismo opioide como alternativa terapéutica.

Introduction. Pruritus is a frequent complication in liver disease and may be difficult to manage. Increased cerebral opiod tone has been proposed as the physiological mechanism that causes pruritus. Opiod antagonism, therefore, leads to an improvement and resolution of symptoms in these patients. Objective. Describe the management of severe pruritus using opiod antagonists in a patient who does not respond to conventional medical management, and conduct a review of the literature.Methodology and results. This is the case of a 50 year-old female patient with a history of autoimmune hepatitis with a five-year history of severe pruritus secondary to cholestasis whichdoes not improve after management with antihistamines, steroids, ursodeoxycholic acid and cholestyramine. It is decided to initiate management with opiod antagonists, starting with an infusion of naloxone for 24 hours with dose escalation from 0.002 μg/kg/min up to 0.2 μg/kg/min, followed by naltrexone up to a dose of 50 mg/day. The therapeutic response was assessed using the visual analog scale (VAS). Within 24 hours ofinitiating the infusion, there is a reduction in the VAS score down to 0/10, with clinical and symptomaticimprovement. Conclusions. The approach to patients with refractorypruritus should include the use of opioidantagonists as a therapeutic option.

Opioid system manipulation during testicular development: results on sperm production and sertoli cells population / Manipulação do sistema opioidérgico durante o desenvolvimento testicular: consequência sobre a produção espermática e a população de células de sertoli

The Sertoli cell has fundamental importance to the development and maintenance of spermatogenesis, as well as it has a directly proportional numerical relationship to sperm production. The proliferative period of this cell in rats occurs between 13 days pre-natal and 21 days pos-natal, when is established the final population in adult animals. The Leydig cell can modulate the Sertoli cell proliferation during fetal and neonatal period through-endorphin. The manipulation of opioidergic system can promote changes in parameters related to development of nervous, endocrine and reproductive systems. By the way, the main purpose of this present work was to compare the effects of the blockade of opioid receptor blocking in Sertoli cells using naltrexone (50 mg kg-1) during fetal and neonatal period in Wistar rats. According to the results, the manipulation of opioidergic system during pre-natal period reduced the total length of seminiferous tubule and Sertoli cell population in adult rats, but sperm production was normal because this cell has had a compensatory response for spermatozoids support capacity.

As células de Sertoli têm fundamental importância para o desenvolvimento e manutenção da espermatogênese, bem como possuem uma relação numérica diretamente proporcional com a produção espermática. O período proliferativo destas células em ratos ocorre entre 13 dias pré-natal e 21 dias pós-natal, resultando na definição da população de células de Sertoli nos animais adultos. As células de Leydig podem modular a proliferação das células de Sertoli durante o período fetal e neonatal por meio da -endorfina. A manipulação do sistema opioidérgico durante esta fase pode promover alterações em parâmetros relacionados com o desenvolvimento dos sistemas nervoso, endócrino e reprodutivo. Em virtude disto, o objetivo do presente trabalho foi comparar os efeitos do bloqueio de receptores opioides nas células de Sertoli, utilizando o naltrexone (50 mg kg-1), durante o período proliferativo destas células em ratos Wistar. De acordo com nossos resultados, a manipulação do sistema opioidérgico durante o período pré-natal reduziu o comprimento total de túbulos seminíferos e a população de células de Sertoli em ratos adultos, porém, a produção espermática foi normal pela resposta compensatória desta célula na capacidade de suporte para espermatozoides.

Drinking in the Context of Health-Sustaining Habits / 가정의학회지

The comprehensive medical care delivered by family physicians should involve education and practice of health-sustaining habits such as diet, exercise, relaxation etc. as well as drug prescription. Among those, problem drinking is one of the most frequent issues encountered in health promoting sessions. However they are not competent to cover the realm of counseling in problem drinking in a continuous way. The drinking problems go up, unnoticed and uninhibited, to the self-destructive stages by the process of denial and avoidance on the part of patient as well as therapists. The explanation by which moderate drinking can't be easily embedded into healthy life styles and the practical strategies for dealing with problem drinkers and alcohol dependents will be presented in the context of health-sustaining habits.

Ensaio clínico duplo-cego randomizado e placebocontrolado com naltrexona e intervenção breve no tratamento ambulatorial da dependência de álcool / A double blind, randomized and placebo-controlled clinical trial with naltrexone and brief intervention in outpatient treatment of alcohol dependence

OBJETIVO: O objetivo deste estudo é avaliar a eficácia da naltrexona com intervenção breve em pacientes com dependência de álcool. MÉTODO: Este estudo é um ensaio clínico randomizado, duplo-cego, placebo-controlado de 12 semanas. A amostra de 71 pacientes foi dividida randomicamente em dois grupos (um recebendo naltrexona e outro placebo). Sujeitos dependentes de álcool foram tratados com 50 mg de naltrexona ou placebo diariamente por 12 semanas. Ambos os grupos de tratamento receberam intervenção breve. Os desfechos clínicos primários para este estudo foram taxa de recaída e mudança no padrão de consumo de álcool. RESULTADOS: Na intenção de tratar, menor porcentagem de sujeitos tratados com naltrexona recaíram (3 por cento 21 por cento; p = 0,054). Naltrexona com intervenção breve não foi superior ao placebo para diminuir os dias de consumo (6,2 + 10,6 3,05 + 7,3; p = 0,478), os dias de consumo moderado (0 2,2 + 6,9; p = 0,345) e os dias de consumo pesado (0,03 + 0,2 0,3 + 0,9; p = 0,887). Naltrexona foi bem tolerada. Os efeitos adversos mais frequentes na presente amostra foram: cefaleia (25,4 por cento), sonolência (20,9 por cento), náuseas (16,4 por cento), hiperfagia (16,4 por cento), anorexia (14,9 por cento), ansiedade (10,4 por cento), pirose (10,4 por cento) e irritabilidade (10,4 por cento). CONCLUSÕES: Embora o grupo naltrexona tenha demonstrado tendência para reduzir taxa de recaída (> 5 doses/dia), não foi encontrada nenhuma diferença em outras variáveis de consumo de álcool entre os grupos naltrexona e placebo. Estudos futuros devem examinar a eficácia desse tipo de combinação de tratamento nos cuidados primários de saúde.

OBJECTIVE: The objective of this study is to evaluate the efficacy of naltrexone with brief intervention among patients with alcohol dependence. METHOD: This study is a 12-week randomized, double blind, placebo-controlled clinical trial. The sample of 71 patients was randomly divided in two groups (one receiving naltrexone and the other placebo). Alcohol-dependent subjects were treated with 50 mg of naltrexone or placebo daily for 12 weeks. Both treatment groups received brief intervention. The primary results for this study were relapse rate and change in drinking behaviors. RESULTS: In the intention-to-treat fewer naltrexone treated subjects relapsed (3 percent 21 percent; p = 0.054). Naltrexone with brief intervention was not effective in decreasing drinking days (6.2 + 10.6 3.05 + 7.3; p = 0.478), moderate drinking days (0 2.2 + 6.9; p = 0.345) and heavy drinking days (0.03 + 0.2 0.3 + 0.9; p = 0.887). Naltrexone was well tolerated. The most frequent adverse effects in our sample were: headache (25.4 percent), drowsiness (20.9 percent), nausea (16.4 percent), hyperphagia (16.4 percent), anorexia (14.9 percent), anxiety (10.4 percent), heartburn (10.4 percent) and irritability (10.4 percent). CONCLUSIONS: Although the naltrexone group showed a tendency to reduce relapse rate (> 5 drinks/day), no differences were found in other alcohol consumption variables between naltrexone and placebo groups. Further studies should examine the efficacy of this kind of treatment combination in the primary health care.