Asunto(s)
Alopecia , Liquen Plano , Naltrexona , Humanos , Alopecia/tratamiento farmacológico , Alopecia/patología , Liquen Plano/tratamiento farmacológico , Liquen Plano/diagnóstico , Liquen Plano/patología , Naltrexona/administración & dosificación , Naltrexona/uso terapéutico , Femenino , Administración Oral , Persona de Mediana Edad , Resultado del Tratamiento , Masculino , Adulto , Fibrosis/tratamiento farmacológico , Anciano , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/uso terapéuticoRESUMEN
AIMS: This study aimed to investigate acamprosate and naltrexone dispensing patterns in Australia. METHODS: A 10% representative sample of medications subsidized by the Australian Pharmaceutical Benefits Scheme (PBS) was used to identify individuals who were dispensed naltrexone or acamprosate between January 2006 and December 2023. Data were used to examine concurrent dispensing, medication switching and treatment episode length, as well as changes in prevalence and incidence over time. RESULTS: During the study, we identified 22 745 individuals with a total of 117 548 dispensed prescriptions (45.3% naltrexone, 43.0% acamprosate, and 11.7% concurrent dispensing). Alcohol pharmacotherapy dispensing occurred in 1354 per 100 000 individuals. It is estimated that 2.9% of individuals with an alcohol use disorder in Australia are receiving a PBS-listed pharmacological treatment. For both pharmacotherapies, individuals were most likely to be male (60.0%) and 35-54 years of age (56.0%). Individuals were more likely to switch from acamprosate to naltrexone rather than the reverse. From 2006 and 2023, the number of prevalent individuals treated with an alcohol pharmacotherapy significantly increased, driven mainly the use of naltrexone, which more than doubled over the study period. Incident naltrexone-treated individuals were more likely to remain on treatment for the recommended minimum 3-month period compared to acamprosate treated individuals, although overall dispensing for at least 3 months was low (5.1%). CONCLUSIONS: In Australia between 2006 and 2023, rates of naltrexone dispensing have substantially increased, while acamprosate dispensing showed minimal changes. However, the use of alcohol pharmacotherapies remains low compared with the likely prevalence of alcohol use disorders.
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Acamprosato , Disuasivos de Alcohol , Alcoholismo , Naltrexona , Humanos , Acamprosato/uso terapéutico , Australia/epidemiología , Masculino , Femenino , Naltrexona/uso terapéutico , Persona de Mediana Edad , Adulto , Disuasivos de Alcohol/uso terapéutico , Alcoholismo/tratamiento farmacológico , Alcoholismo/epidemiología , Adulto Joven , Anciano , AdolescenteRESUMEN
Opioid use disorder (OUD) has been linked to macroscopic structural alterations in the brain. The monthly injectable, extended-release formulation of µ-opioid antagonist naltrexone (XR-NTX) is highly effective in reducing opioid craving and preventing opioid relapse. Here, we investigated the neuroanatomical effects of XR-NTX by examining changes in cortical thickness during treatment for OUD. Forty-seven OUD patients underwent structural magnetic resonance imaging and subjectively rated their opioid craving ≤1 day before (pre-treatment) and 11 ± 3 days after (on-treatment) the first XR-NTX injection. A sample of fifty-six non-OUD individuals completed a single imaging session and served as the comparison group. A publicly available [¹¹C]carfentanil positron emission tomography dataset was used to assess the relationship between changes in cortical thickness and µ-opioid receptor (MOR) binding potential across brain regions. We found that the thickness of the medial prefrontal and anterior cingulate cortices (mPFC/aCC; regions with high MOR binding potential) was comparable between the non-OUD individuals and the OUD patients at pre-treatment. However, among the OUD patients, mPFC/aCC thickness significantly decreased from pre-treatment to on-treatment. A greater reduction in mPFC/aCC thickness was associated with a greater reduction in opioid craving. Taken together, our study suggests XR-NTX-induced cortical thickness reduction in the mPFC/aCC regions in OUD patients. The reduction in thickness does not appear to indicate a restoration to the non-OUD level but rather reflects XR-NTX's distinct therapeutic impact on an MOR-rich brain structure. Our findings highlight the neuroplastic effects of XR-NTX that may inform the development of novel OUD interventions.
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Ansia , Preparaciones de Acción Retardada , Giro del Cíngulo , Imagen por Resonancia Magnética , Naltrexona , Antagonistas de Narcóticos , Plasticidad Neuronal , Trastornos Relacionados con Opioides , Tomografía de Emisión de Positrones , Corteza Prefrontal , Humanos , Naltrexona/farmacología , Naltrexona/administración & dosificación , Naltrexona/uso terapéutico , Masculino , Adulto , Femenino , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/patología , Antagonistas de Narcóticos/farmacología , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/uso terapéutico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/diagnóstico por imagen , Plasticidad Neuronal/efectos de los fármacos , Estudios Longitudinales , Ansia/efectos de los fármacos , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/efectos de los fármacos , Persona de Mediana Edad , Receptores Opioides mu/efectos de los fármacos , Fentanilo/administración & dosificación , Fentanilo/análogos & derivadosRESUMEN
Naltrexone is an µ opioid receptor antagonist that is used in alcohol and opiate use disorder. Naltrexone does not constitute tolerance and dependence, and cessation of the drug does not cause withdrawal symptoms. Sustained release form of naltrexone has been developed due to patient compliance issues. There is currently only one sustainedrelease form available in Turkey, which is inserted subcutaneously. In this case report, we present, a probable serious side effect of sustained release naltrexone implant. A 36 years old male with alcohol use disorder, developed a sudden clouding of consciousness one hour after the naltrexone implant application followed by anterograde amnesia in the next 8-10 hours. We were not able to detect any medical or neurological reasons for the altered mental status but after the removal of the naltrexone implant, the symptoms improved. To the best of our knowledge, this is the first case to report clouding of consciousness and anterograde amnesia after naltrexone implantation. Keywords: Naltrexone Implant, Side Effect, Alcohol Use Disorder, Lethargy, Consciousness.
Asunto(s)
Naltrexona , Antagonistas de Narcóticos , Humanos , Naltrexona/efectos adversos , Naltrexona/administración & dosificación , Naltrexona/uso terapéutico , Masculino , Antagonistas de Narcóticos/efectos adversos , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/uso terapéutico , Adulto , Alcoholismo/complicaciones , Alcoholismo/tratamiento farmacológico , Diagnóstico Diferencial , Inconsciencia/inducido químicamente , Implantes de Medicamentos/efectos adversosRESUMEN
The rising prevalence of obesity is of major concern. There are currently 5 Food and Drug Administration-approved medications for the treatment of obesity: orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide 3.0 mg, and semaglutide 2.4 mg. Surgical options such as bariatric surgery and endoscopic surgery induce more durable weight loss than pharmacotherapy or lifestyle interventions alone. However, patients often experience weight regain and weight loss plateau after surgery. The addition of multimodal or multihormonal pharmacotherapy is a promising tool to address these challenges. The optimal timing of obesity pharmacotherapy with surgical and endoscopic interventions requires further investigation.
Asunto(s)
Fármacos Antiobesidad , Naltrexona , Obesidad , Pérdida de Peso , Humanos , Fármacos Antiobesidad/uso terapéutico , Naltrexona/uso terapéutico , Cirugía Bariátrica/métodos , Orlistat/uso terapéutico , Fentermina/uso terapéutico , Liraglutida/uso terapéutico , Bupropión/uso terapéutico , Topiramato/uso terapéutico , Péptidos Similares al Glucagón/uso terapéuticoRESUMEN
AIMS: We conducted a proof-of-concept randomized controlled trial of the mu-opioid receptor antagonist, naltrexone, augmented with the alpha-1 adrenergic receptor antagonist, prazosin, for alcohol use disorder in veterans. We sought a signal that the naltrexone plus prazosin combination regimen would be superior to naltrexone alone. METHODS: Thirty-one actively drinking veterans with alcohol use disorder were randomized 1:1:1:1 to naltrexone plus prazosin (NAL-PRAZ [n = 8]), naltrexone plus placebo (NAL-PLAC [n = 7]), prazosin plus placebo (PRAZ-PLAC [n = 7]), or placebo plus placebo (PLAC-PLAC [n = 9]) for 6 weeks. Prazosin was titrated over 2 weeks to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS. Naltrexone was administered at 50 mg QD. Primary outcomes were the Penn Alcohol Craving Scale (PACS), % drinking days (PDD), and % heavy drinking days (PHDD). RESULTS: In the NAL-PRAZ condition, % reductions from baseline for all three primary outcome measures exceeded 50% and were at least twice as large as % reductions in the NAL-PLAC condition (PACS: 57% vs. 26%; PDD: 51% vs. 22%; PHDD: 69% vs. 15%) and in the other two comparator conditions. Standardized effect sizes between NAL-PRAZ and NAL-PLAC for each primary outcome measure were >0.8. All but one participant assigned to the two prazosin containing conditions achieved the target prazosin dose of 16 mg/day and maintained that dose for the duration of the trial. CONCLUSION: These results suggest that prazosin augmentation of naltrexone enhances naltrexone benefit for alcohol use disorder. These results strengthen rationale for an adequately powered definitive randomized controlled trial.
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Antagonistas de Receptores Adrenérgicos alfa 1 , Alcoholismo , Quimioterapia Combinada , Naltrexona , Antagonistas de Narcóticos , Prazosina , Prueba de Estudio Conceptual , Humanos , Naltrexona/uso terapéutico , Naltrexona/administración & dosificación , Prazosina/uso terapéutico , Prazosina/administración & dosificación , Masculino , Persona de Mediana Edad , Alcoholismo/tratamiento farmacológico , Antagonistas de Narcóticos/uso terapéutico , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Antagonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Femenino , Adulto , Resultado del Tratamiento , Veteranos , Método Doble CiegoRESUMEN
The aim of this study is to determine if extended-release, bioabsorbable, subcutaneous naltrexone (NTX) implants can mitigate respiratory depression after an intravenous injection (IV) of fentanyl. Six different BIOabsorbable Polymeric Implant Naltrexone (BIOPIN) formulations, comprising combinations of Poly-d,l-Lactic Acid (PDLLA) and/or Polycaprolactone (PCL-1 or PCL-2), were used to create subcutaneous implants. Both placebo and naltrexone implants were implanted subcutaneously in male dogs. The active naltrexone implants consisted of two doses, 644 mg and 1288 mg. A challenge with IV fentanyl was performed in 33 male dogs at 97-100 days after implantation. Following the administration of a 30 µg/kg intravenous fentanyl dose, the placebo cohort manifested a swift and profound respiratory depression with a ~50% reduction in their pre-dose respiratory rate (RR). The BIOPIN NTX-implanted dogs were exposed to escalating doses of intravenous fentanyl (30 µg/kg, 60 µg/kg, 90 µg/kg, and 120 µg/kg). In contrast, the dogs implanted with the BIOPIN naltrexone implants tolerated doses up to 60 µg/kg without significant respiratory depression (<50%) but had severe respiratory depression with fentanyl doses of 90 µg/kg and especially at 120 µg/kg. Bioabsorbable, extended-release BIOPIN naltrexone implants are effective in mitigating fentanyl-induced respiratory depression in male canines at about 3 months after implantation. This technology may also have potential for mitigating fentanyl-induced respiratory depression in humans.
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Implantes Absorbibles , Fentanilo , Naltrexona , Antagonistas de Narcóticos , Insuficiencia Respiratoria , Perros , Animales , Fentanilo/administración & dosificación , Fentanilo/efectos adversos , Masculino , Naltrexona/administración & dosificación , Naltrexona/farmacología , Insuficiencia Respiratoria/inducido químicamente , Insuficiencia Respiratoria/prevención & control , Proyectos Piloto , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/farmacología , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Preparaciones de Acción RetardadaRESUMEN
This study assessed the ability of α1 and α2-adrenergic drugs to decrease fentanyl-induced locomotor and ventilatory depression. Rats were given saline or fentanyl, followed by: (1) naltrexone, (2) naloxone, (3) nalmefene, (4) α1 agonist phenylephrine, (5) α1 antagonist prazosin, (6) α1D antagonist BMY-7378, (7) α2 agonist clonidine, (8) α2 antagonist yohimbine or (9) vehicle. All µ-opioid antagonists dose-dependently reversed fentanyl-induced locomotor and ventilatory depression. While the α1 drugs did not alter the effects of fentanyl, clonidine dose-dependently decreased locomotion and respiration with and without fentanyl. Conversely, yohimbine given at a low dose (0.3-1â¯mg/kg) stimulated ventilation when given alone and higher doses (>1â¯mg/kg) partially reversed (â¼50â¯%) fentanyl-induced ventilatory depression, but not locomotor depression. High doses of yohimbine in combination with a suboptimal dose of naltrexone reversed fentanyl-induced ventilatory depression, suggestive of additivity. Yohimbine may serve as an effective adjunctive countermeasure agent combined with naltrexone to rescue fentanyl-induced ventilatory depression.
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Fentanilo , Ratas Sprague-Dawley , Receptores Adrenérgicos alfa 2 , Animales , Fentanilo/farmacología , Masculino , Receptores Adrenérgicos alfa 2/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Ratas , Locomoción/efectos de los fármacos , Analgésicos Opioides/farmacología , Antagonistas de Narcóticos/farmacología , Yohimbina/farmacología , Naltrexona/farmacología , Naltrexona/análogos & derivados , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Respiración/efectos de los fármacosRESUMEN
BACKGROUND: Recently, we demonstrated that nicorandil inhibits mechanical allodynia induced by paclitaxel. In the present study, we evaluated the effect induced by nicorandil in a model of neuropathic pain induced by chronic constriction injury (CCI) in mice. We also investigated putative mechanisms underlying such an effect. METHODS: CCI was induced by three ligatures of the left sciatic nerve. Mechanical allodynia was evaluated by measuring the paw withdrawal threshold with an electronic von Frey apparatus. Concentrations of cytokines and myeloperoxidase activity were determined in the paw tissue, sciatic nerve, and dorsal root ganglia (DRG). RESULTS: Oral administration of two doses of nicorandil (150 mg/kg po), but not equimolar doses of nicotinamide or nicotinic acid, attenuated mechanical allodynia induced by CCI. Nicorandil activity was reduced by previous administration of glibenclamide (40 mg/kg) or naltrexone (5 mg/kg or 10 mg/kg). Two doses of nicorandil (150 mg/kg, po) reduced tumor necrosis factor-α, interleukin-1ß and interleukin-6, but not CXCL-1, concentrations in the paw tissue of CCI mice. Two doses of nicorandil (150 mg/kg, po) reduced concentrations of all these mediators in the sciatic nerve and DRG. Two doses of nicorandil (150 mg/kg, po) also reduced the myeloperoxidase activity in the paw tissue, sciatic nerve, and DRG. CONCLUSIONS: Nicorandil exhibits antiallodynic activity in a model of neuropathic pain induced by CCI. Inhibition of cytokines production and reduction of neutrophils recruitment in paw tissue, sciatic nerve, and DRG as well as activation of ATP-dependent potassium channels and opioidergic pathways, underlie nicorandil antiallodynic activity.
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Citocinas , Modelos Animales de Enfermedad , Ganglios Espinales , Hiperalgesia , Canales KATP , Neuralgia , Nicorandil , Nervio Ciático , Animales , Nicorandil/farmacología , Neuralgia/tratamiento farmacológico , Neuralgia/metabolismo , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Ratones , Nervio Ciático/efectos de los fármacos , Nervio Ciático/metabolismo , Masculino , Citocinas/metabolismo , Canales KATP/metabolismo , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/metabolismo , Gliburida/farmacología , Naltrexona/farmacología , Naltrexona/análogos & derivados , Peroxidasa/metabolismo , Infiltración Neutrófila/efectos de los fármacos , Analgésicos/farmacologíaRESUMEN
The individual physicochemical stabilities of Allopurinol, Clindamycin Hydrochloride, Naltrexone Hydrochloride, Spironolactone and Ursodiol in the proprietary suspending vehicle PCCA SuspendIt® have been previously studied and published by the author. Accordingly, Beyond-Use-Dates (BUDs) of 180 days were assigned to the five drugs based on the results of the respective studies. The data were donated to the United States Pharmacopeia (USP) for possible adoption as Official Compounded Drug Monographs. Following an extensive review process, all five studies were approved and published by the USP. However, due to a lack of microbiological stability information, the BUDs were limited to 90 days. The current study was undertaken as a follow-up project to determine the microbiological stability of these five drugs in PCCA SuspendIt® utilizing the same compounding procedures from the original studies. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The goal was to provide a viable, compounded alternative for Allopurinol, Clindamycin Hydrochloride, Naltrexone Hydrochloride, Spironolactone and Ursodiol in a thixotropic liquid dosage form, with an extended BUD of 6 months to meet patient needs. Given that the physical and chemical stabilities of all five drugs have been previously established and adopted by the USP as official compounded monographs, additional microbiological stability data would allow the official BUDs in the USP to be extended to 180 days to conform to the physicochemical stabilities. The current study showed that the preservative system in PCCA SuspendIt® successfully protected all the suspensions from growth of challenge microorganisms per the USP Chapter <51> AME Test. The results of the current study combined with the previous physicochemical studies demonstrate the following: Allopurinol is physically, chemically and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature over a bracketed allopurinol concentration range of 10 - 20 mg/mL. Clindamycin Hydrochloride is physically, chemically and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature at a concentration of 10-mg/mL of clindamycin. Naltrexone Hydrochloride is physically, chemically and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature, over a bracketed naltrexone hydrochloride concentration range of 0.5 - 5.0 mg/mL. Spironolactone is physically, chemically and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature at a concentration of 5 mg/mL of spironolactone. Ursodiol is physically, chemically and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature, over a bracketed ursodiol concentration range of 50 - 100 mg/mL. Taken collectively, the current study in conjunction with the earlier studies provide viable, compounded alternatives for Allopurinol, Clindamycin Hydrochloride, Naltrexone Hydrochloride, Spironolactone and Ursodiol in the suspending vehicle PCCA SuspendIt in liquid dosage forms, with an extended beyond-use-date to meet patient needs.
Asunto(s)
Alopurinol , Clindamicina , Composición de Medicamentos , Estabilidad de Medicamentos , Naltrexona , Clindamicina/química , Clindamicina/administración & dosificación , Alopurinol/química , Naltrexona/química , Naltrexona/administración & dosificación , Espironolactona/química , Administración OralRESUMEN
PURPOSE: In this study, we aimed to evaluate the safety and effectiveness of naldemedine for treating opioid-induced constipation (OIC) in patients with advanced cancer, who are receiving palliative care, and particularly explored its early effects. METHODS: Palliative care teams and inpatient palliative care units across 14 institutions in Japan were included in this multicenter, prospective, observational study. Patients who were newly prescribed a daily oral dose of 0.2 mg naldemedine were enrolled. The spontaneous bowel movement (SBM) within 24 h after the first dose of naldemedine was considered the primary outcome, whereas, the secondary outcomes included weekly changes in SBM frequency and adverse events. RESULTS: A total of 204 patients were enrolled and 184 completed the 7-day study. The average age of the participants (103 males, 101 females) was 63 ± 14 years. The primary cancer was detected in the lungs (23.5%), gastrointestinal tract (13.7%), and urological organs (9.3%). A considerable proportion of patients (34.8%) had ECOG performance status of 3-4. Most patients were undergoing active cancer treatment, however, 40.7% of the patients were receiving the best supportive care. Within 24 h of the first naldemedine dose, 146 patients (71.6%, 95% CI: 65.4-77.8%) experienced SBMs. The weekly SBM counts increased in 62.7% of the participants. The major adverse events included diarrhea and abdominal pain, detected in 17.6% and 5.4% of the patients, respectively. However, no serious adverse events were observed. CONCLUSION: Conclusively, naldemedine is effective and safe for OIC treatments in real-world palliative care settings. TRIAL REGISTRATION NUMBER: UMIN000031381, registered 20/02/2018.
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Analgésicos Opioides , Naltrexona , Antagonistas de Narcóticos , Neoplasias , Estreñimiento Inducido por Opioides , Cuidados Paliativos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Cuidados Paliativos/métodos , Anciano , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Estreñimiento Inducido por Opioides/tratamiento farmacológico , Naltrexona/análogos & derivados , Naltrexona/uso terapéutico , Naltrexona/administración & dosificación , Naltrexona/efectos adversos , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/uso terapéutico , Antagonistas de Narcóticos/efectos adversos , Japón , Adulto , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Anciano de 80 o más Años , Dolor en Cáncer/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Importance: Obesity affects approximately 19% of women and 14% of men worldwide and is associated with increased morbidity. Antiobesity medications (AOMs) modify biological processes that affect appetite and significantly improve outcomes, such as type 2 diabetes, hypertension, and dyslipidemia. Observations: AOMs should be administered in combination with lifestyle interventions and can be classified according to their mechanisms of action. Orlistat modifies digestive tract absorption and causes gastrointestinal adverse effects, such as oily fecal spotting and urgency, in more than 25% of patients. Centrally acting drugs, such as phentermine-topiramate and naltrexone-bupropion, regulate appetite in the brain and are associated with constipation in approximately 20% of patients, although the incidence of other adverse effects (eg, paresthesia, nausea) varies by medication. Nutrient-stimulated hormone-based medications, such as liraglutide, semaglutide, and tirzepatide, mimic the actions of enteropancreatic hormones that modify central appetite regulation and provide multiple cardiometabolic weight-loss benefits. Adverse effects of these drugs include nausea (28%-44%), diarrhea (21%-30%), and constipation (11%-24%). The relative potency of adult obesity medications has been studied in meta-analyses. Compared with placebo, orlistat was associated with 3.1% greater weight loss (52 randomized clinical trials [RCTs]; 16â¯964 participants), phentermine-topiramate was associated with 8.0% greater weight loss (5 RCTs; 3407 participants), naltrexone-bupropion was associated with 4.1% greater weight loss (6 RCTs; 9949 participants), liraglutide was associated with 4.7% greater weight loss (18 RCTs; 6321 participants), semaglutide was associated with 11.4% greater weight loss (5 RCTs; 4421 participants), and tirzepatide 15 mg was associated with 12.4% greater weight loss (6 RCTs; 1972 participants). Conclusion and Relevance: Obesity is associated with increased morbidity. Antiobesity medications are effective adjunctive therapy to lifestyle changes for improved weight loss and health outcomes.
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Fármacos Antiobesidad , Dieta Saludable , Obesidad , Femenino , Humanos , Masculino , Fármacos Antiobesidad/uso terapéutico , Fármacos Antiobesidad/efectos adversos , Bupropión/uso terapéutico , Bupropión/efectos adversos , Combinación de Medicamentos , Fructosa/análogos & derivados , Fructosa/uso terapéutico , Fructosa/efectos adversos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Lactonas/uso terapéutico , Lactonas/efectos adversos , Liraglutida/uso terapéutico , Liraglutida/efectos adversos , Naltrexona/uso terapéutico , Naltrexona/efectos adversos , Obesidad/dietoterapia , Obesidad/tratamiento farmacológico , Orlistat/uso terapéutico , Fentermina/uso terapéutico , Fentermina/efectos adversos , Topiramato/uso terapéutico , Topiramato/efectos adversos , Pérdida de Peso/efectos de los fármacos , Terapia Combinada/métodosRESUMEN
BACKGROUND: Little is known about how use patterns of medications for opioid use disorder (MOUDs) evolve from pre-incarceration to post-incarceration among incarcerated individuals with opioid use disorder. This article describes pre- and post-incarceration MOUD receipt during a period when naltrexone was the only type of MOUD offered in a state prison system, the Massachusetts Department of Correction (MADOC). METHODS: A retrospective cohort study of individuals with opioid use disorder who had an incarceration episode in MADOC during January 2015 to March 2019. The data source was the Massachusetts Public Health Data Warehouse, a multi-sector data platform that links individual-level data from multiple statewide datasets. We described patterns of MOUD receipt during the four weeks prior to and after an incarceration episode. Multivariable logistic regression models characterized predictors of post-incarceration MOUD receipt. RESULTS: In the male sample (n=691 incarcerations), from the pre- to post-incarceration periods, receipt of buprenorphine increased (14.3 % to 18.3 %), naltrexone increased (5.0 % to 10.5 %), and methadone decreased (4.7 % to 1.7 %). Similarly, in the female sample (n=892 incarcerations), from the pre- to post-incarceration periods, receipt of buprenorphine increased (10.3 % to 12.3 %, naltrexone increased (4.5 % to 9.3 %), and methadone decreased (5.0 % to 2.9 %). Much of the post-release naltrexone receipt occurred among participants in MADOC's pre-release naltrexone program. CONCLUSIONS: MOUD receipt was low but increased slightly in the post-incarceration period. This change was driven by increases in buprenorphine and naltrexone and despite decreases in methadone.
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Encarcelamiento , Antagonistas de Narcóticos , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides , Femenino , Humanos , Masculino , Buprenorfina/uso terapéutico , Estudios de Cohortes , Encarcelamiento/estadística & datos numéricos , Massachusetts/epidemiología , Metadona/uso terapéutico , Naltrexona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Tratamiento de Sustitución de Opiáceos/estadística & datos numéricos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/epidemiología , Prisioneros , Estudios RetrospectivosRESUMEN
Refining clinical trial methodology has become increasingly important as study design is shown to influence treatment efficacy. To maximize the efficiency of randomized clinical trials (RCTs), researchers aim to establish standardized practices. The goal of this systematic review is to describe methodological practices of clinical trials for alcohol use disorder (AUD) over the past 40 years. To achieve this goal, a PubMed search was conducted in April 2023 for RCTs on AUD medications published between July 2018 through April 2023. Resulting studies were combined with a previous search from 1985 through 2018. Inclusion criteria for the RCT studies were: (1) a randomized controlled trial, (2) double or single blinded, (3) placebo or active control condition, (4) alcohol use as the primary endpoint, (5) 4 or more weeks of treatment, and (6) 12 or more weeks of follow-up. In total, methodological data from 139 RCTs representing 19 medications and spanning the past four decades were summarized. Results indicated that the most common medications tested were naltrexone (k = 42), acamprosate (k = 24), and baclofen (k = 11). On average, participants were 74% male and consumed 226 drinks per month pre-randomization. The median length of treatment was 12 weeks (IQR = 12-16; min = 4 max = 52) and the median follow-up duration was 12.5 weeks (IQR: 12-26; min = 7 max = 104). There were two broad domains of outcomes (i.e., abstinence and heavy drinking), with most studies featuring outcomes from both domains (k = 87; 63%). Reporting practices were summarized by decade, revealing an increased enrollment of females, better reporting of race and ethnicity data, and less studies requiring pre-trial abstinence. This review summarizes the current state of the literature on randomized clinical trials for AUD including effect sizes for individual studies and summaries of key methodological features across this representative set of clinical trials.
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Alcoholismo , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Alcoholismo/tratamiento farmacológico , Disuasivos de Alcohol/uso terapéutico , Proyectos de Investigación , Desarrollo de Medicamentos/métodos , Naltrexona/uso terapéuticoAsunto(s)
Alcoholismo , Naltrexona , Antagonistas de Narcóticos , Humanos , Naltrexona/uso terapéutico , Naltrexona/administración & dosificación , Alcoholismo/tratamiento farmacológico , Antagonistas de Narcóticos/uso terapéutico , Antagonistas de Narcóticos/administración & dosificación , Pautas de la Práctica en MedicinaRESUMEN
INTRODUCTION: This study aims to clarify differences in mood, craving, and treatment response between reward and relief/habit individuals in a study of naltrexone, varenicline, and placebo. We hypothesized that relief/habit individuals would have a poorer mood during early abstinence and higher levels of alcohol craving than reward individuals. We hypothesized that reward individuals would demonstrate better drinking outcomes on naltrexone versus placebo. METHODS: Data were culled from a randomized, double-blind, placebo-controlled human trial of 53 individuals (18F/16M) with alcohol use disorder randomized to varenicline (n = 19), naltrexone (n = 15), or matched placebo (n = 19). In this 6-day practice quit trial, participants attempted to abstain from drinking and completed daily diaries. Participants were classified into reward or relief/habit subgroups based on self-reported motivation for drinking. Multilinear models tested differences in mood and alcohol craving between reward and relief/habit individuals. General linear models tested differences between reward and relief/habit individuals' drinking outcomes on each medication versus placebo. RESULTS: Relief/habit individuals showed decreases in positive mood and increases in negative mood over the quit attempt across medications, compared to reward individuals (P's < .05). Reward individuals' tension decreased on naltrexone, while relief/habit individuals' tension remained stable (F = 3.64, P = .03). Reward individuals in the placebo group had higher percent days abstinent than relief individuals in the placebo group (P < .001). DISCUSSION: This study suggests relief/habit individuals' mood worsens during early abstinence. Our finding that reward individuals' tension decreased on naltrexone and increased on placebo may suggest a clinical response to the medication.
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Afecto , Alcoholismo , Ansia , Naltrexona , Recompensa , Vareniclina , Humanos , Naltrexona/uso terapéutico , Masculino , Vareniclina/uso terapéutico , Femenino , Método Doble Ciego , Adulto , Alcoholismo/tratamiento farmacológico , Alcoholismo/psicología , Ansia/efectos de los fármacos , Persona de Mediana Edad , Afecto/efectos de los fármacos , Antagonistas de Narcóticos/uso terapéutico , Consumo de Bebidas Alcohólicas/psicología , Consumo de Bebidas Alcohólicas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Substance use disorders, including alcohol use disorder, are a public health concern that affect more than 150 million people globally. The opioid antagonist naltrexone is being increasingly prescribed to treat opioid use disorder, alcohol use disorder, and chronic pain. Perioperative management of patients on naltrexone is inconsistent and remains a controversial topic, with mismanagement posing a significant risk to the long-term health of these patients. This scoping review was conducted to identify human studies in which the perioperative management of naltrexone was described. This review includes a systematic literature search involving Medline, Medline In-Process, Embase, PsycINFO, and Web of Science. Seventeen articles that describe perioperative naltrexone management strategies were included, including thirteen guidelines, one case report, and three randomized trials. Despite its use in patients with alcohol use disorder and chronic pain, no clinical studies, case reports, or guidelines addressed naltrexone use in these clinical populations. All of the guideline documents recommended the preoperative cessation of naltrexone, irrespective of dose, indication, or route of administration. None of these guideline documents were designed on the basis of a systematic literature search or a Delphi protocol. As described by the primary studies, perioperative pain relief varied depending on naltrexone dose and route of administration, time since last naltrexone administration, and underlying substance use disorder. None of the studies commented on the maintenance of recovery for the patient's substance use disorder in the context of perioperative naltrexone management. The current understanding of the risks and benefits of continuing or stopping naltrexone perioperatively is limited by a lack of high-quality evidence. In patients with risk factors for return to use of opioids or alcohol, the discontinuation of naltrexone should have a strong rationale. Future studies and guidelines should seek to address both acute pain management and maintaining recovery when discussing perioperative naltrexone management strategies.
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Naltrexona , Antagonistas de Narcóticos , Atención Perioperativa , Naltrexona/uso terapéutico , Naltrexona/administración & dosificación , Humanos , Antagonistas de Narcóticos/uso terapéutico , Antagonistas de Narcóticos/administración & dosificación , Atención Perioperativa/métodos , Trastornos Relacionados con Opioides/prevención & control , Manejo del Dolor/métodos , Dolor Postoperatorio/tratamiento farmacológicoRESUMEN
Importance: Serious injection-related infections (SIRIs) cause significant morbidity and mortality. Medication for opioid use disorder (MOUD) improves outcomes but is underused. Understanding MOUD treatment after SIRIs could inform interventions to close this gap. Objectives: To examine rehospitalization, death rates, and MOUD receipt for individuals with SIRIs and to assess characteristics associated with MOUD receipt. Design, Setting, and Participants: This retrospective cohort study used the Massachusetts Public Health Data Warehouse, which included all individuals with a claim in the All-Payer Claims Database and is linked to individual-level data from multiple government agencies, to assess individuals aged 18 to 64 years with opioid use disorder and hospitalization for endocarditis, osteomyelitis, epidural abscess, septic arthritis, or bloodstream infection (ie, SIRI) between July 1, 2014, and December 31, 2019. Data analysis was performed from November 2021 to May 2023. Exposure: Demographic and clinical factors potentially associated with posthospitalization MOUD receipt. Main Outcomes and Measures: The main outcome was MOUD receipt measured weekly in the 12 months after hospitalization. We used zero-inflated negative binomial regression to examine characteristics associated with any MOUD receipt and rates of treatment in the 12 months after hospitalization. Secondary outcomes were receipt of any buprenorphine formulation, methadone, and extended-release naltrexone examined individually. Results: Among 8769 individuals (mean [SD] age, 43.2 [12.0] years; 5066 [57.8%] male) who survived a SIRI hospitalization, 4305 (49.1%) received MOUD, 5919 (67.5%) were rehospitalized, and 973 (11.1%) died within 12 months. Of those treated with MOUD in the 12 months after hospitalization, the mean (SD) number of MOUD initiations during follow-up was 3.0 (1.7), with 956 of 4305 individuals (22.2%) receiving treatment at least 80% of the time. MOUD treatment after SIRI hospitalization was significantly associated with MOUD in the prior 6 months (buprenorphine: adjusted odds ratio [AOR], 16.51; 95% CI, 13.81-19.74; methadone: AOR, 28.46; 95% CI, 22.41-36.14; or naltrexone: AOR, 2.05; 95% CI, 1.56-2.69). Prior buprenorphine (incident rate ratio [IRR], 1.17; 95% CI, 1.11-1.24) or methadone (IRR, 1.89; 95% CI, 1.79-2.01) use was associated with higher treatment rates after hospitalization, and prior naltrexone use (IRR, 0.86; 95% CI, 0.77-0.95) was associated with lower rates. Conclusions and Relevance: This study found that in the year after a SIRI hospitalization in Massachusetts, mortality and rehospitalization were common, and only half of patients received MOUD. Treatment with MOUD before a SIRI was associated with posthospitalization MOUD initiation and time receiving MOUD. Efforts are needed to initiate MOUD treatment during SIRI hospitalizations and subsequently retain patients in treatment.
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Trastornos Relacionados con Opioides , Humanos , Massachusetts/epidemiología , Masculino , Trastornos Relacionados con Opioides/tratamiento farmacológico , Femenino , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Buprenorfina/uso terapéutico , Tratamiento de Sustitución de Opiáceos/estadística & datos numéricos , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/epidemiología , Metadona/uso terapéutico , Adolescente , Adulto Joven , Readmisión del Paciente/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Naltrexona/uso terapéuticoRESUMEN
INTRODUCTION: Medications for opioid use disorder (MOUD) include opioid agonist therapies (OAT) (buprenorphine and methadone), and opioid antagonists (extended-release naltrexone). All forms of MOUD improve opioid use disorder (OUD) and HIV outcomes. However, the integration of services for HIV and OUD remains inadequate. Persistent barriers to accessing MOUD underscore the immediate necessity of addressing pharmacoequity in the treatment of OUD in persons with HIV (PWH). AREAS COVERED: In this review article, we specifically focus on OAT among PWH, as it is the most commonly utilized form of MOUD. Specifically, we delineate the intersection of HIV and OUD services, emphasizing their integration into the United States Ending the HIV Epidemic (EHE) plan by offering comprehensive screening, testing, and treatment for both HIV and OUD. We identify potential drug interactions of OAT with antiretroviral therapy (ART), address disparities in OAT access, and present the practical benefits of long-acting formulations of buprenorphine, ART, and pre-exposure prophylaxis for improving HIV prevention and treatment and OUD management. EXPERT OPINION: Optimizing OUD outcomes in PWH necessitates careful attention to diagnosing OUD, initiating OUD treatment, and ensuring medication retention. Innovative approaches to healthcare delivery, such as mobile pharmacies, can integrate both OUD and HIV and reach underserved populations.
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Analgésicos Opioides , Buprenorfina , Interacciones Farmacológicas , Infecciones por VIH , Metadona , Naltrexona , Antagonistas de Narcóticos , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides , Humanos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , Buprenorfina/administración & dosificación , Tratamiento de Sustitución de Opiáceos/métodos , Antagonistas de Narcóticos/administración & dosificación , Metadona/administración & dosificación , Naltrexona/administración & dosificación , Analgésicos Opioides/administración & dosificación , Preparaciones de Acción Retardada , Accesibilidad a los Servicios de Salud , Estados Unidos , Atención a la Salud/organización & administración , Profilaxis Pre-Exposición/métodos , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/farmacologíaRESUMEN
NTX is FDA-approved for opiate and alcohol use disorders as anti-craving agent. It has been used successfully off-label in other psychiatric indications. Here, we shed some light on these while examining the extant evidence.