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Spironolactone is a diuretic medication originally approved for the treatment of cardiovascular conditions like heart failure, fluid retention, and high blood pressure. However, recent research suggests this medication may also have potential as a new treatment for alcohol use disorder (AUD).
In the United States, approximately 17 million adults struggle with AUD, according to the Agency for Healthcare Research and Quality (AHRQ), making finding effective treatment options of the utmost importance. [1] Traditional treatment options include behavioral therapy and FDA-approved medications, such as naltrexone, disulfiram, and acamprosate. Recently, spironolactone has been garnering attention as a possible addition to this list.
Below, we’ll dive into the details on how spironolactone works for AUD, its current status in AUD treatment, and who this new therapy might benefit.
- Spironolactone is a mineralocorticoid receptor antagonist originally used to manage heart and kidney conditions. Recent studies show that it may reduce alcohol consumption in individuals with AUD.
- Alcohol can interfere with spironolactone’s effects, potentially leading to unwanted side effects.
- Although research is promising, spironolactone is not yet FDA-approved for AUD and requires further research.
Understanding Spironolactone
Spironolactone is a mineralocorticoid receptor (MR) antagonist that is used to manage heart failure, liver disease, high blood pressure, edema (swelling), and certain kidney conditions. It works by blocking aldosterone, a hormone in the renin-angiotensin-aldosterone system that regulates fluid balance and blood pressure. By blocking aldosterone in the kidneys, it prevents sodium reabsorption and, therefore, water retention. Instead, there is increased potassium retention, and this results in overall fluid loss. [2]Â
Research has shown that mineralocorticoid receptors may play a role in alcohol use and cravings. These receptors are found throughout the brain and other organs, and they play a key role in regulating fluid and electrolyte balances. Recent research has found that higher MR signaling is linked to increased alcohol consumption, while MR-blocking strategies might help curb drinking behaviors, making spironolactone a promising potential treatment option for AUD. [3]
Spironolactone as a potential treatment for AUD
As spironolactone blocks mineralocorticoid receptors, researchers began exploring its potential for AUD treatment. Unlike the medications currently approved by the FDA for AUD, it operates through a unique mechanism, potentially making it a promising option for individuals who haven’t responded to other therapies.
Animal studies supported this theory and found that blocking MR activity in the brain reduced alcohol self-administration in male and female rats.[4] However, animal studies should be interpreted with caution, as the same results may not be reproduced in humans.
A 2022 study on the effects of spironolactone on rats, mice, and humans had similarly encouraging results. Researchers found that spironolactone dose-dependently reduced alcohol consumption in male and female mice, as well as in alcohol-dependent rats. Similar reductions were observed in human participants, particularly those who engaged in heavy episodic drinking. [5]
The drug may also help reduce the amount of alcohol individuals consume, as a 2021 study published in Neuropsychopharmacology found that individuals taking spironolactone reduced their alcohol intake by an average of 3.50 drinks per week, compared to 2.74 drinks in untreated individuals. Even more promising is that those consuming more than 7 drinks per week at baseline saw an even greater reduction, meaning spironolactone may work better for individuals with greater alcohol consumption. [3]
Current status of spironolactone in AUD treatment
While these findings are promising, spironolactone is not yet approved by the FDA for AUD treatment. Researchers caution that more clinical trials are needed to confirm its safety and efficacy before it can be widely recommended.
There is currently a double-blind, placebo-controlled study taking place that is evaluating the pharmacokinetics and pharmacodynamics of taking spironolactone and alcohol together and testing the safety and tolerability of spironolactone in individuals with AUD. [6]Â
This is a promising step towards the necessary clinical trials for spironolactone to be further evaluated for potential FDA approval for the treatment of AUD.
Interactions between spironolactone and alcohol
Although spironolactone may reduce alcohol consumption, research has found that combining them can lead to certain complications. According to research, not only is spironolactone one of the most commonly prescribed drugs, but it can also cause serious drug interactions and result in an increased risk of side effects. [7]Â
Because alcohol and spironolactone are diuretics (meaning they cause the body to lose fluids and electrolytes), when taken in combination, they can lead to dehydration. [2]Â
Additionally, because spironolactone works by increasing potassium reuptake in exchange for sodium excretion, it is possible to develop potentially fatal hyperkalemia (high potassium levels). Dehydration due to alcohol consumption can worsen the risk of hyperkalemia. This is especially true in patients with impaired kidney function. The combination of alcohol and spironolactone necessitates close laboratory monitoring to identify electrolyte abnormalities. [2]
Spironolactone is also used to lower blood pressure, and alcohol has variable effects on blood pressure. Their use in combination may lead to dangerous blood pressure fluctuations, which can lead to dizziness or fainting.
Both substances are metabolized by the liver. Combining them may increase the risk of liver damage, particularly among individuals with preexisting liver conditions (which is very common among individuals with AUD). [2]Â
Potential side effects and safety concerns
While spironolactone is generally well-tolerated, it does come with the risk of side effects. Common side effects include:
- Dehydration
- Electrolyte imbalances (high potassium levels or low sodium levels)
- Gastrointestinal problems (nausea, vomiting, diarrhea, or loss of appetite)
- Headache, drowsiness, confusion
- Skin rashes
- Breast tenderness or menstrual irregularities in women
- Men may experience gynecomastia, loss of libido, or general feminization [8]Â
If you experience any of these side effects, it is crucial to speak with your prescriber. It is important to only take spironolactone under the guidance of a licensed medical practitioner.
Alternatives to spironolactone for AUD
Although spironolactone has a growing body of research to support its use in AUD, not all providers will prescribe it off-label for this use at this time, given the limited time evidence available and the lack of incorporation into medical guidelines. There are currently three FDA-approved medications for AUD:
- Naltrexone: It reduces alcohol cravings and the pleasurable effects of drinking.
- Disulfiram: It causes unpleasant reactions (like nausea and flushing) if alcohol is consumed to discourage its use.
- Acamprosate: It helps restore the balance of the neurotransmitter GABA after alcohol is stopped. [3]Â
Though not FDA-approved to treat AUD, medications such as gabapentin, topiramate, or baclofen may be used in the treatment of AUD.
Behavioral treatments for AUD also exist. This includes group therapy, inpatient rehabilitation, outpatient individual therapy, and self-help courses. Behavioral treatments should be used in conjunction with medication for the best outcomes. [2]
Who might benefit from spironolactone for AUD?
Based on research, spironolactone may be most effective for individuals who:
- Consume more than 7 alcoholic drinks per week
- Engage in binge drinking or heavy episodic alcohol use
- Have not responded well to traditional AUD medications
- Have high blood pressure, heart failure, or other conditions that spironolactone already treats
Individuals who have kidney disease or severe liver disease, low blood pressure, or high potassium levels should not take this medication.
It is important to discuss the potential benefits and risks with your healthcare provider before starting any new medications.
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