| Title: |
Prazosin and cyproheptadine in combination in the treatment of alcohol use disorder: A randomized, double‐blind, placebo‐controlled trial |
| Authors: |
Aubin, Henri-Jean; Berlin, Ivan; Guiraud, Julien; Bruhwyler, Jacques; Batel, Philippe; Perney, Pascal; Trojak, Benoit; Bendimerad, Patrick; Guillou Landreat, Morgane; Bisch, Michaël; Bronnec, M.; Labarrière, Damien; Delsart, Dominique; Questel, Frank; Moirand, Romain; Bernard, Philippe; Trovero, Fabrice; Pham, Hang Phuong; Tassin, Jean-Pol; Puech, Alain |
| Contributors: |
Centre de recherche en épidémiologie et santé des populations (CESP); Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse; AP-HP. Université Paris Saclay-AP-HP. Université Paris Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay; Hôpital Paul Brousse; AP-HP. Université Paris Saclay; CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Sorbonne Université (SU); Universiteit van Amsterdam (UvA); Université de Montpellier (UM); Hôpital Universitaire Carémeau Nîmes (CHU Nîmes); Centre Hospitalier Universitaire de Nîmes (CHU Nîmes); Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon); Université Bourgogne Franche-Comté COMUE (UBFC); Hôpitaux La Rochelle Ré Aunis Groupe hospitalier littoral Atlantique; Soins Primaires, Santé Publique, Registre des cancers de Bretagne Occidentale (EA7479 SPURBO); Université de Brest (UBO EPE)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut Brestois Santé Agro Matière (IBSAM); Université de Brest (UBO EPE)-Université de Brest (UBO EPE); Centre Psychothérapique de Nancy Laxou (CPN); Nantes Université (Nantes Univ); Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes); Université de Tours (UT); Centre Hospitalier Regional d'Orléans (CHRO); Sans affiliation; Université Paris Diderot - Paris 7 (UPD7); Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal Paris; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Nutrition, Métabolismes et Cancer (NuMeCan); Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Key-Obs SAS France; Parean biotechnologies; Institut de Biologie Paris Seine (IBPS); Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS); Bpifrance; Biocodex Microbiota Foundation; Horizon 2020 Framework Programme: H2020‐SMEInst‐2018‐2020‐2, Nr 873252 |
| Source: |
ISSN: 0965-2140. |
| Publisher Information: |
CCSD; Wiley |
| Publication Year: |
2024 |
| Collection: |
Université de Versailles Saint-Quentin-en-Yvelines: HAL-UVSQ |
| Subject Terms: |
Alcohol reduction; alcohol use disorder; cyproheptadine; prazosin; randomized controlled trial; risk drinking level; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; Background and aims: Pre-clinical studies suggest that the simultaneous blockade of the α1b and 5HT2A receptors may be effective in reducing alcohol consumption. This study aimed to assess the efficacy and safety of prazosin (α1b blocker) and cyproheptadine (5HT2A blocker) combination in decreasing total alcohol consumption (TAC) in alcohol use disorder (AUD).Design, setting and participants: This was a double-blind, parallel group, placebo-controlled, Phase 2, randomized clinical trial conducted in 32 addiction treatment centres in France. A total of 108 men and 46 women with severe AUD took part.Intervention: Participants were randomly assigned to one of the following 3-month treatments: (1) low-dose group (LDG) receiving 8 mg cyproheptadine and 5 mg prazosin extended-release (ER) formulation daily; (2) high-dose group (HDG) receiving 12 mg cyproheptadine and 10 mg prazosin ER daily; and (3) placebo group (PG) receiving placebo of cyproheptadine and prazosin ER. A total of 154 patients were randomized: 54 in the PG, 54 in the LDG and 46 in the HDG.Measurements: The primary outcome was TAC change from baseline to month 3.Findings: A significant main treatment effect in the change in TAC was found in the intent-to-treat population (P = 0.039). The HDG and LDG showed a benefit in the change in TAC from baseline to month 3 compared with PG: -23.6 g/day, P = 0.016, Cohen's d = -0.44; -18.4 g/day, P = 0.048 (Bonferroni correction P < 0.025), Cohen's d=-0.36. In a subgroup of very high-risk drinking-level participants (> 100 g/day of pure alcohol for men and > 60 g/day for women), the difference between the HDG and the PG in the primary outcome was -29.8 g/day (P = 0.031, Cohen's d = -0.51). The high and low doses were well-tolerated with a similar safety profile.Conclusions: A randomized controlled trial of treatment of severe alcohol use disorder with a cyproheptadine-prazosin combination for 3 months reduced drinking by more than 23 g per day compared with placebo. A higher dose ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/38597214; PUBMED: 38597214 |
| DOI: |
10.1111/add.16484 |
| Availability: |
https://hal.science/hal-04574679; https://hal.science/hal-04574679v1/document; https://hal.science/hal-04574679v1/file/Addiction%20-%202024%20-%20Aubin%20-%20Prazosin%20and%20cyproheptadine%20in%20combination%20in%20the%20treatment%20of%20alcohol%20use%20disorder%20A.pdf; https://doi.org/10.1111/add.16484 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.3848E4C2 |
| Database: |
BASE |