Two repurposed medications cut drinking significantly in severe alcohol use disorder
STUDY: Aubin HJ et al, Addiction 2024;119:1211–1223, PMID: 40176122
STUDY TYPE: Randomized, double-blind, placebo-controlled trial
FUNDING: Kinnov Therapeutics (this is a phase II trial, and they are developing this as a branded combo pill)
Background
Prazosin is a α1b-adrenergic blocker for blood pressure. Cyproheptadine is an antihistamine that modulates serotonin much like mirtazapine does. Together, they may reduce drinking by re-coupling noradrenergic and serotonergic systems dysregulated by chronic alcohol use. Indeed, animal studies show they reduce various addictions when used together, but not on their own. This is the first human trial to test them.
The Study
154 adults with severe alcohol use disorder were randomized to low-dose (prazosin 5 mg + cyproheptadine 8 mg daily), high-dose (prazosin 10 mg + cyproheptadine 12 mg daily), or placebo for 12 weeks. No prior detoxification was required. The primary outcome was total daily alcohol consumption (TAC).
Both doses outperformed placebo. High-dose reduced daily drinking by 23.6 g compared to placebo (effect size, cohen’s d = 0.44); low-dose by 18.4 g (Cohen’s d = 0.36). In the heaviest drinkers, the high-dose advantage grew to nearly 30 g/day (Cohen’s d = 0.51). Alcohol craving (Obsessive Compulsive Drinking Scale) and depressive symptoms (Beck Depression Inventory) also improved.
Weight gain — about 2.5 kg — was the most notable side effect, driven by cyproheptadine’s appetite-stimulating properties. Orthostatic hypotension was rare and similar across all groups.
Practice Implications
Both these meds treat nightmares, so the combo may have a role in PTSD with comorbid alcohol use.
Meanwhile, stick with FDA approved options, but this combo is a good alternative if those do not work.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
