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Clinical Trial
. 2024 Jul;119(7):1211-1223.
doi: 10.1111/add.16484. Epub 2024 Apr 10.

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

Henri-Jean Aubin  1 , Ivan Berlin  2 , Julien Guiraud  3   4 , Jacques Bruhwyler  5 , Philippe Batel  6 , Pascal Perney  7 , Benoît Trojak  8 , Patrick Bendimerad  9 , Morgane Guillou  10 , Michaël Bisch  11 , Marie Grall-Bronnec  12 , Damien Labarrière  13 , Dominique Delsart  14 , Frank Questel  15 , Romain Moirand  16 , Philippe Bernard  17 , Fabrice Trovero  18 , Hang Phuong Pham  19 , Jean-Pol Tassin  20 , Alain Puech  17   20
Affiliations
Clinical Trial

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

Henri-Jean Aubin et al. Addiction. 2024 Jul.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT04108104.

Keywords: Alcohol reduction; alcohol use disorder; cyproheptadine; prazosin; randomized controlled trial; risk drinking level.

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References

REFERENCES

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