Naltrexone

Naltrexone is the most widely used Food and Drug Administration (FDA) approved medication to reduce alcohol drinking.  Naltrexone works by blocking the effect of endorphins, the natural opioids normally released by drinking.  Therefore, the pleasure that drinking gives will be less. Naltrexone is effective at reducing alcohol consumption and relapse, and seems to work particularly well with individuals who have a strong family history of alcoholism.  I like to prescribe naltrexone because its effects are well known, and it is relatively safe. Naltrexone works best at 50 mg/day, although for the first dose or two, many patients start at 25 mg.  Injectable depo naloxone is a long-acting form of naltrexone which can be very helpful for people who have trouble remembering to take pills. The effects of the injectable drug can last for more than a month. For someone who recognizes that they are drinking too much, taking naltrexone an hour before drinking has been shown to help.  This method of using naltrexone is called the Sinclair Method, which  has brought hope to thousands. 

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Dr. John David Sinclair (1943-2015) was an alcohol researcher who studied naltrexone, a medication that blocks the opiate or endorphin induced pleasure normally caused by alcohol.  Sinclair's research demonstrated that animals trained to drink alcohol would unlearn, or extinguish their drinking behavior if alcohol were given with naltrexone.  Similarly, Dr. Sinclair found that people given naltrexone before they drank alcohol could sometimes extinguish their excessive drinking behavior, and essentially "unlearn" their habit of drinking.

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According to Sinclair, for naltrexone to help people stop drinking excessively, they need to drink with naltrexone in their system so they would no longer get the anticipated pleasure or “buzz” from endorphins released by alcohol.   Over time, they would gradually unlearn, or extinguish their drinking behavior. This gradual reduction in drinking is called pharmacological extinction and it forms the basis for the Sinclair method of treating people with alcohol use disorder.

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For many patients, over many years, the Sinclair method has been effective. As with any treatment, however, it does not work for everyone.  It might not work for you; there is no way to know in advance.  Long experience with the method, however, supports its use even though we cannot be certain it will work, or even be safe, in any given individual. As with most medications, there may be side effects (e.g. headache, nausea) as the body gets used to the medication.

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The key to the Sinclair method is that the person with alcohol use disorder must take naltrexone 50 mg, 1 hour before drinking - every time they drink, for the rest of their life.  Many, but not all, people treated this way will gradually reduce their consumption of alcohol. Sinclair found that this gradual reduction in drinking permitted heavy drinkers to stop drinking entirely without the need for acute detoxification. 

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The Sinclair method describes a very specific method of using naltrexone. Commonly, when a physician prescribes naltrexone, it is for a patient who has detoxed off alcohol entirely; Patients are advised to completely abstain from alcohol while taking the naltrexone.  However, Sinclair did not believe that this was the correct advice for people who were still drinking.  Sinclair's research suggested that counseling patients with different Cognitive Behavioral Therapy (CBT) methods during naltrexone studies made a critical difference in the results: when patients were merely admonished to be abstinent, the naltrexone had no effect.  However, when patients were encouraged to drink moderately, naltrexone was effective.

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The Sinclair method requires that no alcohol drinking ever occur without naltrexone in the blood stream.  For the method to work, people must not drink unless they have taken naltrexone an hour before.  Compliance with this rule is 100% non-negotiable.  The process of the Sinclair method can take anywhere from four to eight months to reach full extinction of cravings, sometimes even longer.  Two to three weeks is not long enough.  If someone should forget to take their naltrexone, they will often know it when they take a drink - they may feel an extremely strong 'hit' from the very first mouthful.  If someone forgets, the method requires that they stop drinking immediately, take the tablet of naltrexone, and wait an hour before finishing the drink.

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The optimum dosage for naltrexone has been found to be one 50mg tablet, one hour prior to drinking. A 5o mg dose of naltrexone will usually do its job for about 10-12 hours - the protection of naltrexone has a limited effect. Also, naltrexone may not work as well for someone taking strong drinks; the rapid effect of concentrated alcohol may overcome the opiate blocking effect of the naltrexone, rendering it less effective. As with most medications, there may be  side effects (e.g. headache, nausea) as the body gets used to the medication.  For the first couple of doses, taking a half a tablet will often minimize these effects. To further minimize these side effects, patients often drink lots of water and eat a meal before taking the naltrexone.   Most people are not bothered by side effects after they have taken the medication for several weeks. Another negative issue with naltrexone is that while someone is taking it, opioid medications used for emergency pain treatment will not work.  

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Naltrexone does not block alcohol intoxication. Instead, it may enhance aspects of intoxication, such as impairment of peripheral vision and divided attention. If someone gets into trouble from drinking, the safest course of action is to never drink again - abstinence is the best advice in this situation. However, abstaining completely is not acceptable or a realistic goal for many people. The targeted use of medication before drinking recognizes this reality, which is why I find it helpful for many people with alcohol use disorder. 

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An important distinction of the Sinclair Method of naltrexone use is that on days when drinking will definitely not occur, the individual does not take the naltrexone but instead takes part in a pleasurable activity.​  This is an important benefit that comes with using naltrexone only before drinking - the effect that it has to reduce the natural opiates in the brain, (endorphins), is only working on the days people drink alcohol.  In this manner, naltrexone is not acting to reduce the pleasure of healthy activities that take place on days when naltrexone is not taken.

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Naltrexone can commonly cause a mild headache or nausea, but these symptoms usually resolve after the first week or so.  Many people find that if they eat a meal with the naltrexone, they don’t notice any nausea. Although it rarely happens, Naltrexone can also cause liver problems, so liver function is monitored with blood tests, and is not given when the liver is severely damaged. Another issue with naltrexone is that if someone taking it requires emergency pain relief,  the effect of opiate pain medicines will be blocked.  In this case, alternate methods of pain control will be necessary.  Carrying a wallet card which notifies emergency personnel about naltrexone use is a good idea; if someone is using opiates, and takes a naltrexone pill with opiates in their system, they will immediately develop severe withdrawal symptoms. That’s why patients should wait several days after stopping opiates before taking their first naltrexone pill.

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Acamprosate
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Acamprosate is an FDA approved medication which has been shown to help alcoholics stop drinking. Acamprosate can reduce persistent symptoms of abstinence such as insomnia, anxiety, restlessness, and the state of unease and dissatisfaction that comes with not drinking alcohol. Acamprosate is chemically similar to an amino acid and acts on the glutamate neurotransmitter system in the brain. Acamprosate has relatively mild side effects, which are typically limited to stomach upsets or diarrhea. Inconvenience can be the major disadvantage to taking Acamprosate because it must be taken three times a day. Acamprosate doesn’t affect the liver, so it’s often used if someone cannot tolerate naltrexone.

Disulfiram

Disulfiram, also known as Antabuse, blocks the normal metabolism of alcohol so that when someone drinks while taking this medication, they experience a very unpleasant reaction that can include flushing, nausea, vomiting, headaches, chest pain, blurred vision, confusion, respiratory difficulty, and palpitations. This reaction can last for 12 hours and persist as long as 14 days after the last dose of disulfiram. There is a risk of liver damage with disulfiram, so patients taking this drug must have regular blood tests. Although disulfiram has been used for helping alcoholics stay sober for more than 30 years, the severity of this reaction has limited its widespread use.  It is sometimes useful in selected high-risk situations to prevent a relapse.

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Topiramate

Topiramate was originally used to treat epilepsy, and is now also FDA approved as a treatment for migraines. It is used “off label” to help alcoholics stop drinking. Topiramate can reduce craving and is particularly helpful early in early abstinence to help alcoholics avoid returning to regular drinking.  Side effects may include drowsiness, dizziness, loss of coordination, loss of appetite, cognitive impairment, weight loss, tingling of the hands/feet, diarrhea, eye problems and nausea.  Topiramate may decrease the effectiveness of estrogen-containing oral contraceptives, and taking topiramate in the 1st trimester of pregnancy may increase risk of cleft lip/cleft palate in the infant. Therefore, women of childbearing age who use this drug must use alternative, non-hormone based forms of contraception. Topiramate can cause a reduction in sweating, putting people at greater risk of heat related problems like heatstroke.

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Baclofen
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Baclofen is an FDA approved muscle relaxant sometimes used “off label” to reduce alcohol craving; it is very commonly used in France and Australia.  Studies suggest that baclofen is helpful in alcoholic patients who have extreme anxiety.  Importantly, baclofen can be given safely to patients with evidence of liver damage, so it may be especially helpful for very heavy drinkers.  Some patients report having nausea, vertigo, transient sleepiness, and abdominal pain on baclofen.

 
Ondansetron
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Ondansetron is approved by the FDA to treat nausea, particularly nausea associated with chemotherapy. It has also been used “off label” to treat alcoholics with an early onset type of alcoholism, or alcoholism associated with a specific gene which can influence serotonin function.  Adverse effects associated with ondansetron include diarrhea and headache. Ondansetron can adversely affect the electrical conduction of the heart, so it is avoided in patients with underlying heart conditions.

 
Gabapentin

Gabapentin has been approved by FDA for the treatment of epilepsy, and neuropathic pain.  It has been used “off label” for alcoholism and other drugs of abuse, however its use is limited because it may itself become a drug of abuse. Gabapentin can cause drowsiness, dizziness, headache, and fatigue, but these adverse effects are less common at lower doses.

 
Prazosin
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Prazosin, is an older medication used for hypertension and for men with urine flow issues associated with the prostate gland.  Prazosin is also used “off label” in post traumatic stress disorder and to reduce the impact of the terrifying dreams that accompany this disorder.  In one research study, when patients were given it for this purpose, they noticed they lost their desire to drink.  This led to other studies suggesting that prazosin may help alcoholics maintain sobriety.  Prazosin is a difficult medicine to take, however, because it must be taken three times a day, and the dose must be increased slowly over several weeks.  As a blood pressure medicine, it can cause excessively low blood pressure, and the most common side effect of prazosin is fainting.  Fainting may occur when standing suddenly.  

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Omega-3 fatty acids
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Scientists who study the brain know the importance of omega-3 fat, especially the long omega-3 fats DHA and EPA.  Although these essential fatty acids are critical components of the nervous system, they are not abundant in the typical American diet, and levels are depleted further by excessive alcohol use.  Many patients report marked improvement in their mood and thought process once they start taking fish oil, which is the common source of these fats.  One of my projects when I worked at NIH was to measure the brain utilization of radiolabeled DHA using PET scanning. My research determined that the half-life of DHA in the brain was greater than 2 years, suggesting that the fats we eat today could have an influence for years to come.  For an overview of omega-3 fatty acids, you can refer to a chapter I wrote in the book “Low-Cost Approaches to Promote Physical and Mental Health”, pp.87-101.

Sources of Omega 3 Fatty Acid

The American Psychiatric Association recommends that individuals with mood, impulse-control or psychotic disorders should consume at least 1 gram of EPA + DHA per day.  The most natural way to benefit from omega-3 fatty acids is to eat lots of seafood every day, particularly deep sea oily fish like salmon, mackerel, and sardines.  However, for many people, taking fish oil is a more practical approach. Individuals in recovery commonly begin by taking 3 grams of Omega 3 fatty acids as fish oil.  May people take a daily dose of 5 grams or more as this higher dose may be necessary to provide an anti-inflammatory effect.  Look for a product that contains both EPA and DHA daily, and add the milligrams of each together to determine the total amount of omega-3 fat it contains.  Vegan forms of DHA are available. For many people, flax and chia may be an inexpensive alternative source of omega-3 fat.  However, most research has been done with DHA and EPA, found in fish and not in flax and chia.