Naltrexone for Alcoholism 2017-08-12T18:32:43+00:00

Naltrexone for Alcoholism

Naltrexone was approved by the FDA as a treatment for Alcohol Dependence in 1994.  However, it was initially approved for the treatment of Opioid Dependence in 1984, due to the fact that the medication works by blocking the effects of opioids.  This includes naturally occurring opiates in the brain known as Endorphins.  When alcohol is consumed, normally these endorphins are released, which causes the drinker to experience please.  When these receptors are blocked, the experience of enjoyment is less when alcohol is consumed.

Evidence has demonstrated that when Naltrexone is combined with counseling and other therapeutic interventions, it can decrease

  • The amount of alcohol consumed during one occasion (i.e. binges).
  • The number of days spent drinking
  • Drinking that results in negative consequences

Naltrexone does not make you sick when you combine it with alcohol, the way Antabuse (disulfiram) does.  It does not alter the metabolism or absorption of alcohol in any way, nor does it prevent patients from becoming intoxicated if they drink alcohol.

Because Naltrexone blocks opioid receptors, opiate pain medications such as Morphine, Oxycodone, Percocet,  and Vicodin will  not be effective.  If treatment with opioids is necessary, the naltrexone will need to be stopped for 2 to 3 days prior to starting the opioids.  Patients should wait 5-10 days after taking Naltrexone before starting an opiate.

Naltrexone does not affect over-the-counter pain medications such as Ibuprofen (Advil), Acetaminophen (Tylenol), or aspirin.

It is recommended that patients taking Naltrexone carry a safety identification card indicating that they are taking the medication, in case of an emergency.

Naltrexone Side Effects

Naltrexone is generally well tolerated, but like all medications, it has the potential to cause side effects. The frequency of serious side effects is very low. The most common side effects are gastrointestinal, including upset stomach, nausea, vomiting, and diarrhea. The frequency of side effects is below:

  • nausea (10%)
  • headache (7%)
  • dizziness (4%)
  • nervousness (4%)
  • fatigue (4%)
  • insomnia (3%)
  • vomiting (3%)
  • anxiety (2%)
  • somnolence (2%)

Most likely, you won’t have any side effects, but if you do, they usually go away with continued use. There are a few things that can be done, if a side effect persists:

1. Lower the dose. This will give the body time to adjust to the new medication. Once you feel comfortable, you can try increasing it back to a more therapeutic dose.
2. Divide the dose. Instead of taking 50 mg once daily, you could take 25 mg twice daily.
3. Take with food.
4. Combine the naltrexone with an over-the-counter medication that addresses the side effect. Usually this means taking Pepto-Bismol.

Naltrexone in Pregnancy

It is in Pregnancy Category C, which officially means, “Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.”

For obvious reasons, it is not easy to design a conclusive study that involves giving pregnant woman various medications.

Initial Medical Workup

Prior to starting Naltrexone, it is generally a good idea to have the following:
  • Liver Functioning Tests (LFT)
  • Physical Examination (if indicated)
  • Pregnancy Test

After 1 month of taking Naltrexone, a follow-up LFT can be ordered.  Based on the results, additional labs can be ordered every 3 to 6 months.  More frequent monitoring may be necessary if there is liver damage or other medical concern.

Research has demonstrated that liver functioning generally improves in patients taking Naltrexone, because alcohol is far more damaging to the liver.

Naltrexone Dosage for Sinclair Method

The usual dosage for Naltrexone is 50 mg daily.  It may be appropriate to start at 25 mg daily for several days, in order to give your body time to adjust to the medication.  This reduces the likelihood of side effects.

Occasionally, a patient may need doses higher than 50 mg daily.  Even at this dose, the available evidence shows that Naltrexone is safe, well tolerated, and effective.  Prior to adjusting the dosage, additional Liver Function Tests should be obtained.

It is recommended that patients taking Naltrexone carry a safety identification card indicating that they are taking the medication, in case of an emergency.

Naltrexone Alcoholism Studies

Abstract

AIMS:  The role of craving for alcohol as a response to alcohol treatment is not well understood. We examined daily diary ratings of craving over the course of 28 days among individuals participating in an inpatient substance abuse treatment program.

METHODS:  Participants were alcohol dependent patients (n = 100) in the Hazelden residential treatment program who were offered and agreed to take naltrexone and an age- and gender-matched comparison group (n = 100) of alcohol-dependent patients in the same program who declined the offer of treatment with naltrexone. Changes in craving over time were compared between the two groups.

RESULTS:  The naltrexone-treated group reported a more rapid decrease in craving than the usual care group.

CONCLUSIONS:  The change in the trajectory of craving is consistent with prior reports suggesting that craving reduction is a mechanism of naltrexone‘s efficacy in treating alcohol dependence. Providing naltrexone to individuals seeking treatment for alcohol dependence may accelerate a reduction in their craving, consistent with a primary target of many addiction treatment programs.

SHORT SUMMARY:  Craving ratings by 100 residential patients taking naltrexone for alcohol dependence were compared to ratings by 100 patients who did not take naltrexone. Craving for alcohol decreased more rapidly in the patients taking naltrexone. Providing naltrexone to individuals seeking treatment for alcohol dependence may accelerate a reduction in craving, which may benefit treatment efforts.

Abstract

Naltrexone is a narcotic antagonist that has been shown to reduce alcohol craving and alcohol use in patients with alcohol dependence. It should not be used as exclusive treatment but only as an adjunct to a comprehensive program that includes psychologic and social treatment approaches such as those in Alcoholics Anonymous or professional programs. The two most serious complications of naltrexone therapy are the precipitation of narcotic withdrawal in patients taking narcotics, and hepatotoxicity. The latter complication occurs only at dosages much higher than the 50 mg per day recommended for treatment of alcohol dependence. Alcohol is known to enhance opioid receptors. Evidently, naltrexone blockade of these receptors results in reduced craving for alcohol, less of a “high” while drinking and less alcohol use.

Abstract

BACKGROUND:

In almost 2 decades of naltrexone research for treating alcoholism, there have been 29 published randomized placebo-controlled trials of opioid antagonists, primarily naltrexone, for the treatment of alcohol dependence. The present review builds on prior systematic reviews while maximizing the number of included studies to date, for the purpose of resolving inconsistencies in naltrexone‘s reported efficacy across trials. Clinical trial results in this article are evaluated by the type of outcome measure used to determine naltrexone‘s treatment advantage, that is, measures related to reducing heavy drinking versus those related to increasing abstinence.

METHODS:

We conducted a Medline search to identify double-blind studies from 1990 to the present (2006) that evaluated the use of anopiate antagonist for the treatment of alcohol dependence. There were 29 studies identified, representing 5997 alcohol-dependent patients, which met our study inclusion criteria for this review. Studies were evaluated in this review on 4 prespecified drinking outcomes-2 related to “any drinking” and 2 related to “heavy or excessive drinking.”

RESULTS:

In the treatment of alcohol dependence, we found that 19 (70%) of 27 clinical trials that measured reductions in “heavy or excessive drinking” demonstrated an advantage for prescribing naltrexone over placebo, whereas only 9 (36%) of 25 clinical trials that measured abstinence or “any drinking” found an advantage for medication over placebo.

CONCLUSION:

The majority of double-blind clinical trials in the literature favored prescribing naltrexone for alcohol dependence to reduce heavy drinking. This finding is consistent with our understanding of naltrexone‘s mechanism of action of decreasing excessive drinking by reducing the reward associated with drinking alcohol. Thus, we conclude that outcome measures related to heavy or excessive drinking are most relevant to defining naltrexone‘s therapeutic effects. Factors influencing naltrexone response (treatment adherence and distinct patient subgroups) are also discussed.

There is increasing evidence supporting a link between the endogenous opioid system and excessive alcohol consumption. Acute or light alcohol consumption stimulates the release of opioid peptides in brain regions that are associated with reward and reinforcement and that mediate, at least in part, the reinforcing effects of ethanol. However, chronic heavy alcohol consumption induces a central opioid deficiency, which may be perceived as opioid withdrawal and may promote alcohol consumption through the mechanisms of negative reinforcement. The role of genetic factors in alcohol dependency is well recognized, and there is evidence that the activity of the endogenous opioid system under basal conditions and in response to ethanol may play a role in determining an individual’s predisposition to alcoholism. The effectiveness of opioid receptor antagonists in decreasing alcohol consumption in people with an alcohol dependency and in animal models lends further support to the view that the opioid system may regulate, either directly or through interactions with other neurotransmitters, alcohol consumption. A better understanding of the complex interactions between ethanol, the endogenous opioids and other neurotransmitter systems will help to delineate the neurochemical mechanisms leading to alcoholism and may lead to the development of novel treatments.

There are few effective medications available for the treatment of alcohol use disorders (AUDs). To date, the opioid antagonist, naltrexone, is the most effective in reducing alcohol consumption in combination with behavioral therapy. Naltrexone has high affinity for the mu opioid peptide receptor (MOP-R) with moderate activity at the delta opioid peptide receptor (DOP-R) and kappa opioid peptide receptor (KOP-R). Preclinical studies suggest that the MOP-R plays a significant role in ethanol-mediated behaviors, however, there is evidence suggesting the DOP-R may be a better therapeutic target for treating AUDs. This chapter will review studies investigating the role of the opioid receptors in ethanol-mediated behaviors with the view of identifying improved therapeutics for the treatment of AUDs.

Biochemical and behavioral evidence indicate that the dopaminergic mesolimbic system plays a key role in the mechanisms of reinforcement and reward elicited by alcohol (ethanol) and other drugs of abuse. In addition, the dopaminergic activity of the nigrostriatal pathway has been proposed to determine brain sensitivity to ethanol, a process which could be associated to drug addiction. Besides dopamine, several neurotransmitters and neuromodulators are involved in ethanol reinforcement mechanisms, including gamma aminobutyric acid (GABA), glutamate, serotonin, acetylcholine and opioid peptides (enkephalins, endorphins and dynorphins). Ethanol and opioids share several pharmacological properties and exhibit similar behavioral effects in animals and humans. These and other studies suggest that the alcohol reinforcing properties are due, at least in part, to the ethanolinduced activation of endogenous opioidergic systems. This activation could in turn increase the hedonic value and the reinforcing effects of the drug. Thus, ethanol-induced changes in opioidergic transmission could contribute to alcohol intoxication and to the neuroadaptive responses produced by the long-lasting exposure to the drug. Opioidergic transmission may be altered by ethanol at different levels, including biosynthesis, release and inactivation of endogenous opioid peptides, as well as their binding to their receptors. Several studies suggest that mu and delta opioid receptors play a key role in ethanol reinforcement and dependence. Therefore, enkephalins and β-endorphin could physiologically mediate ethanol actions in the brain and play a major role in high drug use behavior. During the last few years, our research group has focused on the role of the endogenous opioid systems in these processes. Evidence obtained in our laboratory suggests that enkephalins and β-endorphin differentially and selectively participate in ethanol reinforcement and dependence.