Prazosin and cyproheptadine in combination in the treatment of alcohol use disorder: A randomized, double-blind, placebo-controlled trial.

Autor: Aubin HJ; Université Paris-Saclay, AP-HP, Inserm, CESP, Villejuif, France., Berlin I; Hopital Pitie-Salpetriere, Sorbonne Université, Paris, France., Guiraud J; University of Amsterdam, Amsterdam, the Netherlands.; Vergio, Clichy, France., Bruhwyler J; ECSOR sa/nv, Brussels, Belgium., Batel P; Centre Hospitalier Camille Claudel, La Couronne, France., Perney P; Hôpital Carémeau, Nîmes, Université Montpellier 1, Villejuif, France., Trojak B; Centre hospitalier Universitaire Dijon Bourgogne, Université Bourgogne Franche-Comté, Besançon, France., Bendimerad P; Addiction Department, Groupe Hospitalier Littoral Atlantique, La Rochelle, France., Guillou M; ER 7479 SPURBO, Université Bretagne Occidentale, Brest, France., Bisch M; Centre Psychothérapique de Nancy, Addiction Medicine department, Laxou, France., Grall-Bronnec M; Addictology and Liaison Psychiatry Department, Nantes University Hospital, Nantes and Tours Universities, Nantes, France., Labarrière D; Centre Hospitalier Régional, Orléans, France., Delsart D; Private practice, Bersée, France., Questel F; Université Paris Diderot, GH Lariboisière-Saint-Louis-Fernand Widal, Paris, France., Moirand R; Université Rennes, Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), UF Addictologie, Rennes, France., Bernard P; Kinnov-Therapeutics, Orléans, France., Trovero F; SAS Key-Obs, Orléans, France., Pham HP; Parean Biotechnologies, Saint-Malo, France., Tassin JP; Inserm, Sorbonne-Université, Laboratoire Neuroscience Paris-Seine, Paris, France., Puech A; Kinnov-Therapeutics, Orléans, France.; Inserm, Sorbonne-Université, Laboratoire Neuroscience Paris-Seine, Paris, France.
Jazyk: angličtina
Zdroj: Addiction (Abingdon, England) [Addiction] 2024 Jul; Vol. 119 (7), pp. 1211-1223. Date of Electronic Publication: 2024 Apr 10.
DOI: 10.1111/add.16484
Abstrakt: 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 combination was associated with a larger magnitude of drinking reduction than a lower dose combination while showing similar safety profile.
(© 2024 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)
Databáze: MEDLINE
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