Naltrexone

Naltrexone is an opioid receptor antagonist. By blocking mu- opioid receptors, naltrexone reduces levels of dopamine (the major reward neurotransmitter in the brain) and reduces alcohol intake. 

The effectiveness of naltrexone to reduce the rate of relapse has been well documented in literature. Meta-analyses of randomised controlled trials indicate naltrexone is effective in reducing alcohol consumption with a number needed to treat (NNT) of 12 over placebo for reducing the risk of returning to heavy drinking. 

The current approach is to use naltrexone as part of a more comprehensive treatment plan that may include psychosocial interventions.

Patients with a moderate to severe AUD and who are medically stable are suitable for naltrexone. Naltrexone may be more effective for preventing relapse to heavy drinking than for maintaining abstinence however this remains to be confirmed. 

Patients currently using opioids or who require opiate-based pain relief are not suitable. Due to its antagonist properties at the mu-opioid receptor, naltrexone will precipitate acute opioid withdrawal in patients currently using opioids. For the same reason, being on naltrexone will render opioid analgesia ineffective. 

Naltrexone is contraindicated for people with acute hepatitis or severe liver failure. Patients should be close to or under the upper limit of normal on liver function tests (see below). 

There are no well controlled studies of the safety of naltrexone during pregnancy or lactation.

Naltrexone is a mu-opioid receptor antagonist and induces precipitated opiate withdrawal in patients who are currently opiate dependent. It is contraindicated in patients with current or recent use of opioid medication (e.g. codeine, morphine, oxycodone, methadone).

Naltrexone is a long-acting drug and will block the effects of opioids when they are used after commencement of naltrexone treatment. Naltrexone should be discontinued 48-72 hours prior to any situation where opioid analgesia may be required (e.g. in patients undergoing elective surgery).

Naltrexone does not appear to alter the absorption or metabolism of alcohol; however, some patients have reported nausea after drinking alcohol while taking naltrexone.

The interaction of naltrexone and most other medications has not been tested. However, caution should be exercised when combining naltrexone with other drugs known to have hepatotoxicity (e.g. disulfiram).

Concurrent administration of naltrexone with antidepressants appears to be safe.

Naltrexone dosing is recommended to begin 3-7 days after the patient’s last drink and after resolution of acute withdrawal symptoms. Starting naltrexone after the resolution of withdrawal symptoms may prevent the possibility of worsening of withdrawal symptoms (e.g., nausea/vomiting) and also to aid distinguish between side-effects and withdrawal symptoms. 

It is not known whether patients with a diagnosis of AUD achieve better outcomes if abstinent before taking naltrexone. However, some period of abstinence (at least 3 days) was the requirement of most clinical trials investigating the effectiveness of naltrexone.  

Due to hepatotoxicity and potential rise of liver enzymes, it is pivotal that liver function tests are close to or under the upper limit of normal before commencement of naltrexone (alanine aminotransferase concentrations should not be greater than 3–5 times the normal limit).

Naltrexone is formulated in tablets of 50mg, with the recommended dose being 50mg (1 tablet/day orally) with meals. It may be preferable to commence with ½ tablet (25mg/day) for several days and increase to 50mg after any adverse effects have subsided.

In Australia, naltrexone is only available in tablets. Naltrexone is subsidised by the pharmaceutical benefit scheme (PBS).

The most appropriate duration of treatment continuation in a patient with moderate to severe AUD is not yet known. The usual treatment period used in majority of randomised controlled studies as well as in clinical practice is 3-6 months and in some cases up to 12 months. 

The decision on the treatment duration should be made on a case-by-case basis between the patient and doctor, based on side effects, history of relapse, social and family circumstances, and other individual factors.

Naltrexone is usually well tolerated. Common adverse effects include nausea, headache, dizziness, fatigue, nervousness, insomnia, vomiting, and anxiety in about 10 percent of patients. These generally subside with time (usually days). 

Based on clinical practice, the following strategies may help reduce the impact of potential side effects on treatment outcome: 

1. Patient education about expected side effects and duration.  
2. Timing of doses: establish a routine; ideally taken in the morning with food or splitting the dosage between the morning and evening.  
3. Gradual introduction of medication (25mg for 1-2 days).  
4. Dose reduction (half tablets at 25mg/day).  
5. Slow titration.  
6. Stopping the medication for three to four days before reintroducing it at a lower dose.  

Beginning treatment once the major features of alcohol withdrawal have subsided (generally 3-5 days after drinking cessation) may be helpful to distinguish between prolonged alcohol withdrawal symptoms and side effects of naltrexone. 

Due to hepatotoxicity and potential rise of liver enzymes, it is important to perform liver function tests periodically.   

Treatment should continue even if the patient lapses; psychosocial relapse prevention techniques should be used to deal with the lapse or relapse (see Chapter 9). 

Monitoring and attending to physical and mental health is important.

There is no evidence of a withdrawal syndrome or development of dependence following the use of naltrexone. Psychosocial relapse prevention should continue beyond the end of pharmacotherapy.