Endoxifen is NOT Effective for Binge Drinking or Alcohol Use Disorder
Endoxifen, a selective estrogen receptor modulator, has no established role in treating binge drinking or alcohol use disorder (AUD) and is not mentioned in any current clinical guidelines or evidence-based treatment protocols for these conditions. There is no clinical trial data, FDA approval, or guideline recommendation supporting its use for AUD or binge drinking 1.
Evidence-Based Pharmacotherapy for AUD
The established pharmacological treatments for AUD include three FDA-approved medications 1:
FDA-Approved First-Line Options:
- Naltrexone (50 mg/day orally or 380 mg monthly injectable): Opioid receptor antagonist with NNT of 20 to prevent return to any drinking 1
- Acamprosate (666 mg three times daily): NMDA receptor antagonist with NNT of 12, no hepatic metabolism, and no reported hepatotoxicity 1
- Disulfiram: Not recommended in patients with alcohol-associated liver disease due to hepatotoxicity concerns 1
Off-Label Medications with Evidence:
- Topiramate (75-400 mg/day): GABA augmentation and glutamate antagonism, demonstrates consistent efficacy in reducing heavy drinking 1, 2
- Gabapentin (600-1,800 mg/day): Modulates GABA activity, renally excreted 1
- Baclofen (30-60 mg/day): The only AUD medication tested in RCT with cirrhotic patients, showing improved abstinence rates 1
Clinical Approach
For patients with binge drinking or AUD without liver disease, start with naltrexone 50 mg daily as first-line pharmacotherapy 3, 2. Naltrexone reduces return to any drinking by 5% and binge-drinking risk by 10% 3.
For patients with significant liver disease, use acamprosate or baclofen 1. Acamprosate has no hepatic metabolism and no hepatotoxicity, while baclofen has demonstrated safety and efficacy specifically in cirrhotic patients 1.
Important Caveats:
- Medications should be combined with behavioral interventions (CBT, motivational interviewing, or motivational enhancement therapy) for optimal outcomes 1
- Naltrexone undergoes hepatic metabolism and carries hepatotoxicity concerns in patients with alcohol-associated liver disease 1
- Baclofen may impair mentation and should be avoided in patients with hepatic encephalopathy 1
- Despite evidence of efficacy, medications are prescribed to less than 9% of patients who would benefit from them 3
Why Endoxifen is Not Used
Endoxifen is a selective estrogen receptor modulator (active metabolite of tamoxifen) used primarily in breast cancer treatment. Its mechanism of action—estrogen receptor modulation—has no established connection to the neurotransmitter systems involved in AUD pathophysiology (GABA, glutamate, opioid, dopamine systems) 1. No preclinical or clinical studies have evaluated endoxifen for alcohol-related conditions.