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Multicenter Observational/Exploratory Study Addressed to the Evaluation of the Effectiveness and Safety of Pharmacological Therapy in Opioid-Dependent Patients in Maintenance Therapy in Southern Italy

A multicenter-observational study was performed to assess the effectiveness of rac-methadone, levomethadone, and buprenorphine in opioid-dependent patients in polytherapy in Southern Italy. The primary endpoint was the reduction of urinary positivity to the substances and the maintaining doses. Pati...

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Autores principales: Maqoud, Fatima, Fabio, Giada, Ciliero, Nunzio, Antonacci, Marina, Mastrangelo, Francesca, Sammarruco, Giorgio, Cataldini, Roberto, Schirosi, Gabriella, De Fazio, Salvatore, Tricarico, Domenico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878258/
https://www.ncbi.nlm.nih.gov/pubmed/35214192
http://dx.doi.org/10.3390/pharmaceutics14020461
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author Maqoud, Fatima
Fabio, Giada
Ciliero, Nunzio
Antonacci, Marina
Mastrangelo, Francesca
Sammarruco, Giorgio
Cataldini, Roberto
Schirosi, Gabriella
De Fazio, Salvatore
Tricarico, Domenico
author_facet Maqoud, Fatima
Fabio, Giada
Ciliero, Nunzio
Antonacci, Marina
Mastrangelo, Francesca
Sammarruco, Giorgio
Cataldini, Roberto
Schirosi, Gabriella
De Fazio, Salvatore
Tricarico, Domenico
author_sort Maqoud, Fatima
collection PubMed
description A multicenter-observational study was performed to assess the effectiveness of rac-methadone, levomethadone, and buprenorphine in opioid-dependent patients in polytherapy in Southern Italy. The primary endpoint was the reduction of urinary positivity to the substances and the maintaining doses. Patients (N = 266, age = 44.80 ± 5.65, male = 79.70%, female = 20.30%) have been recruited. At recruitment, 75% of them were on treatment with rac-methadone, levomethadone, and buprenorphine/naloxone. The patients were grouped into three clusters. The levomethadone patients of Cluster A (N patients = 211), after 180 days, showed stability in urinary methadone positivity, with a marked decrease in heroin −53 ± 4%, cannabinol’s −48 ± 2%, and cocaine −37 ± 6% positivity, with no differences between treatments. A lower QTcF value of 426 ± 8.4 ms was recorded in the levomethadone patients (delta = −19 ms) vs. rac-methadone, at significantly lower doses of levomethadone (−34%, −50.2% in males) (p < 0.05). The Cluster B data were collected from 37 patients, with a high prevalence of comorbidity infections (HIV/HCV/HPV), monitored for 21 months during COVID-19. High doses of levomethadone (58.33 ± 31.58 mg/day) were needed to stabilize those that were negative for opioids and cannabinoids, in contrast to the rac-methadone and buprenorphine/naloxone patients that showed positive toxicology. Eighteen patients of the Cluster C in double diagnosis (major depressive 38.90%, bipolar 27.78%, and schizophrenia 16.67%) were stabilized with high doses of racemate 97.5 ± 8 mg/day, 51.8 ± 5 mg/day of levomethadone (−46.8% vs. rac-methadone; −71% in men), and 2.5 ± 1 mg/day of buprenorphine/naloxone. Three patients in remission were treated with tapering doses of levomethadone. Significantly reduced QTcF values were recorded with levomethadone (delta −32 ms vs. rac-methadone) in the bipolar patients, as well as the schizophrenia patients in remission (delta −45.19 ms vs. rac-methadone). Our patients were safely stabilized. Levomethadone, compared to the racemate, contributes to reducing the illicit use, especially of opioids and cannabinoids at significantly lower doses with cardiovascular safety, which, in bipolar patients, is clinically significant.
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spelling pubmed-88782582022-02-26 Multicenter Observational/Exploratory Study Addressed to the Evaluation of the Effectiveness and Safety of Pharmacological Therapy in Opioid-Dependent Patients in Maintenance Therapy in Southern Italy Maqoud, Fatima Fabio, Giada Ciliero, Nunzio Antonacci, Marina Mastrangelo, Francesca Sammarruco, Giorgio Cataldini, Roberto Schirosi, Gabriella De Fazio, Salvatore Tricarico, Domenico Pharmaceutics Article A multicenter-observational study was performed to assess the effectiveness of rac-methadone, levomethadone, and buprenorphine in opioid-dependent patients in polytherapy in Southern Italy. The primary endpoint was the reduction of urinary positivity to the substances and the maintaining doses. Patients (N = 266, age = 44.80 ± 5.65, male = 79.70%, female = 20.30%) have been recruited. At recruitment, 75% of them were on treatment with rac-methadone, levomethadone, and buprenorphine/naloxone. The patients were grouped into three clusters. The levomethadone patients of Cluster A (N patients = 211), after 180 days, showed stability in urinary methadone positivity, with a marked decrease in heroin −53 ± 4%, cannabinol’s −48 ± 2%, and cocaine −37 ± 6% positivity, with no differences between treatments. A lower QTcF value of 426 ± 8.4 ms was recorded in the levomethadone patients (delta = −19 ms) vs. rac-methadone, at significantly lower doses of levomethadone (−34%, −50.2% in males) (p < 0.05). The Cluster B data were collected from 37 patients, with a high prevalence of comorbidity infections (HIV/HCV/HPV), monitored for 21 months during COVID-19. High doses of levomethadone (58.33 ± 31.58 mg/day) were needed to stabilize those that were negative for opioids and cannabinoids, in contrast to the rac-methadone and buprenorphine/naloxone patients that showed positive toxicology. Eighteen patients of the Cluster C in double diagnosis (major depressive 38.90%, bipolar 27.78%, and schizophrenia 16.67%) were stabilized with high doses of racemate 97.5 ± 8 mg/day, 51.8 ± 5 mg/day of levomethadone (−46.8% vs. rac-methadone; −71% in men), and 2.5 ± 1 mg/day of buprenorphine/naloxone. Three patients in remission were treated with tapering doses of levomethadone. Significantly reduced QTcF values were recorded with levomethadone (delta −32 ms vs. rac-methadone) in the bipolar patients, as well as the schizophrenia patients in remission (delta −45.19 ms vs. rac-methadone). Our patients were safely stabilized. Levomethadone, compared to the racemate, contributes to reducing the illicit use, especially of opioids and cannabinoids at significantly lower doses with cardiovascular safety, which, in bipolar patients, is clinically significant. MDPI 2022-02-21 /pmc/articles/PMC8878258/ /pubmed/35214192 http://dx.doi.org/10.3390/pharmaceutics14020461 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Maqoud, Fatima
Fabio, Giada
Ciliero, Nunzio
Antonacci, Marina
Mastrangelo, Francesca
Sammarruco, Giorgio
Cataldini, Roberto
Schirosi, Gabriella
De Fazio, Salvatore
Tricarico, Domenico
Multicenter Observational/Exploratory Study Addressed to the Evaluation of the Effectiveness and Safety of Pharmacological Therapy in Opioid-Dependent Patients in Maintenance Therapy in Southern Italy
title Multicenter Observational/Exploratory Study Addressed to the Evaluation of the Effectiveness and Safety of Pharmacological Therapy in Opioid-Dependent Patients in Maintenance Therapy in Southern Italy
title_full Multicenter Observational/Exploratory Study Addressed to the Evaluation of the Effectiveness and Safety of Pharmacological Therapy in Opioid-Dependent Patients in Maintenance Therapy in Southern Italy
title_fullStr Multicenter Observational/Exploratory Study Addressed to the Evaluation of the Effectiveness and Safety of Pharmacological Therapy in Opioid-Dependent Patients in Maintenance Therapy in Southern Italy
title_full_unstemmed Multicenter Observational/Exploratory Study Addressed to the Evaluation of the Effectiveness and Safety of Pharmacological Therapy in Opioid-Dependent Patients in Maintenance Therapy in Southern Italy
title_short Multicenter Observational/Exploratory Study Addressed to the Evaluation of the Effectiveness and Safety of Pharmacological Therapy in Opioid-Dependent Patients in Maintenance Therapy in Southern Italy
title_sort multicenter observational/exploratory study addressed to the evaluation of the effectiveness and safety of pharmacological therapy in opioid-dependent patients in maintenance therapy in southern italy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8878258/
https://www.ncbi.nlm.nih.gov/pubmed/35214192
http://dx.doi.org/10.3390/pharmaceutics14020461
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