What is/are Naltrexone?
Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. It is marketed in generic form as its hydrochloride salt, naltrexone hydrochloride, and marketed under the trade names Revia and Depade. In some countries including the United States, a once-monthly extended-release injectable formulation is marketed under the trade name Vivitrol. Also in the US, Methylnaltrexone Bromide, a closely related drug, is marketed as Relistor, for the treatment of opioid induced constipation.
Naltrexone should not be confused with naloxone (which is used in emergency cases of opioid overdose) nor nalorphine. Using naloxone in place of naltrexone can cause acute opioid withdrawal symptoms; conversely, using naltrexone in place of naloxone in an overdose can lead to insufficient opioid antagonism and fail to reverse the overdose.
The main use of naltrexone is for the treatment of alcohol dependence. Naltrexone was approved for the treatment of alcohol dependence in 1994, following publication of the first two randomized, controlled trials in 1992. Since then a number of studies have confirmed its efficacy in reducing frequency and severity of relapse to drinking. The multi-center COMBINE study showed the usefulness of naltrexone in a primary care setting, without adjunct psychotherapy.
The standard regimen is one 50 mg tablet per day.
Naltrexone has been shown to reduce relapse rates after abstinence in multiple clinical studies. Additionally there is evidence that naltrexone helps reduce heavy drinking when used in people who continue drinking while taking naltrexone. Some authors argue that naltrexone may be more effective when used during active drinking than in abstinence, termed the Sinclair Method.
Naltrexone helps patients overcome opioid addiction by blocking the drugs’ euphoric effects. Unlike when used for alcohol dependence (discussed above), naltrexone has little effect on opioid cravings. Naltrexone has in general been better studied for alcohol dependence than in treating opioid dependence. It is also more frequently used for alcohol, despite originally being approved by the FDA in 1984 for opioid addiction.
A recent review of studies suggests that more research is needed to show naltrexone's effectiveness in treating opioid dependence (and to compare naltrexone to other options such as methadone and buprenorphine). While some patients do well with the oral formulation, there is a drawback in that it must be taken daily, and a patient whose cravings become overwhelming can obtain opioid intoxication simply by skipping a dose before resuming abuse. Due to this issue, the usefulness of oral naltrexone in opioid dependence is limited by the low retention in treatment. Oral naltrexone remains an ideal treatment only for a small part of the opioid-dependent population, usually the ones with an unusually stable social situation and motivation (e.g., dependent health care professionals). Naltrexone treats the physical dependence on opioids, but further psychosocial interventions (such as counselling and group therapy) are often required to enable people to maintain abstinence.
Rapid opioid detoxification
Naltrexone is sometimes used for rapid detoxification ("rapid detox") regimens for opioid dependence. The principle of rapid detoxification is to induce opioid-receptor blockage while the patient is in a state of impaired consciousness, so as to attenuate the withdrawal symptoms experienced by the patient. Rapid detoxification under general anaesthesia (sometimes called "ultra-rapid detox") involves an unconscious patient and requires intubation and external ventilation. Rapid detoxification is also possible under lighter sedation. The rapid detoxification procedure is followed by oral naltrexone daily for up to 12 months for opioid dependence management. There are a number of practitioners who will use a naltrexone implant, usually placed in the lower abdomen, to replace the oral naltrexone. This implant procedure has not been shown scientifically to be successful in "curing" subjects of their addiction, though it does provide a better solution than oral naltrexone for medication compliance reasons. There is currently scientific disagreement as to the safety of this procedure, as well as whether this procedure should be performed under light sedation or general anesthesia, due to the rapid and sometimes severe withdrawal that occurs.
Rapid detoxification has been criticised by some for its questionable efficacy in long-term opioid dependence management. Rapid detoxification has often been misrepresented as a one-off "cure" for opioid dependence, when it is only intended as the initial step in an overall drug rehabilitation regimen. Rapid detoxification is effective for short-term opioid detoxification, but is approximately 10 times more expensive than conventional detoxification procedures. Aftercare can also be an issue, since at least one well-known center in the United States reported that they will remove an implant from any patient arriving in their facility before admission.
Naltrexone is sometimes used in the treatment of depersonalization disorder. While studies have suggested it is less effective than naloxone for treating depersonalization, naloxone is impractical for daily use because it must be injected intravenously. A 2005 naltrexone study demonstrated an average of 30% reduction of depersonalization symptoms, as measured by 3 validated dissociation scales. Most of the efforts in studying naltrexone for depersonalization thus far have been directed by Dr. Daphne Simeon at the Mount Sinai School of Medicine.
"Low dose naltrexone" (LDN) describes the "off-label" use of naltrexone at low doses for diseases not related to chemical dependency or intoxication, such as multiple sclerosis. Preliminary research suggests low dose naltrexone may be useful in preventing opioid tolerance and dependence when combined with an opioid, reduce the severity of opioid withdrawal, or improve fibromyalgia symptoms, though much more research needs to be done before it can be recommended for clinical use.
Although there have been dramatic claims about its efficacy in treating a wide range of diseases including cancer and HIV, these claims are not generally supported by scientific evidence. This treatment has gotten significant attention on the Internet, especially through websites run by organizations promoting its use.
A single-blind randomized, two-group clinical trial of Low Dose Naltrexone for HIV/AIDS was conducted in Mali from March 2008 to March 2010, published in the Journal of AIDS and HIV Research. The authors concluded that adding LDN to a three-antiretroviral regime used improved the recovery rate of CD4 count, suggesting "further exploration of LDN as part of an HIV+ treatment regime is warranted."
A single-cohort study of Low Dose Naltrexone in 55 HIV-positive asymptomatic untreated patients with CD4 counts between 350-600 was conducted in 2008-2009. This study showed CD4 percentages maintained without loss over the study's nine-month period.
A study done by The Chicago Stop Smoking Research Project at the University of Chicago found that Naltrexone did not help to improve a subjects chance of attaining smoking cessation when compared to a placebo.
Some studies suggest that self-injurious behaviors present in persons with developmental disabilities (including autism) can sometimes be remedied with naltrexone.In these cases, it is believed that the self-injury is being done to release beta-endorphin, which binds to the same receptors as heroin and morphine. By removing the "rush" generated by self-injury, the behavior may stop.
There are indications that naltrexone might be beneficial in the treatment of impulse control disorders such as kleptomania, compulsive gambling, or trichotillomania (compulsive hair pulling). A 2008 case study reported successful use of naltrexone in suppressing and treating an internet pornography addiction.
Countering adverse effects of interferon alpha
Naltrexone is effective in suppressing the cytokine type mediated adverse neuropsychiatric effects of interferon alpha therapy.
he most common side effects reported with naltrexone are non-specific gastrointestinal complaints such as diarrhea and abdominal cramping.
Naltrexone has been reported to cause liver damage (when given at doses higher than recommended). It carries an FDA boxed warning for this rare side effect. Due to these reports, some physicians may check liver function tests prior to starting naltrexone, and periodically thereafter. Concerns for liver toxicity initially arose from a study of non-addicted obese patients receiving 300mg of naltrexone. Subsequent studies have suggested limited toxicity in other patient populations.
Naltrexone should not be started prior to several (typically 7-10) days of abstinence from opioids. This is due to the risk of acute opioid withdrawal if naltrexone is taken, as naltrexone will displace most opioids from their receptors. The time of abstinence may be shorter than 7 days, depending on the half-life of the specific opioid taken. Some physicians use a naloxone challenge to determine whether an individual has any opioids remaining. The challenge involves giving a test dose of naloxone and monitoring for opioid withdrawal. If withdrawal occurs, naltrexone should not be started.
It is important that one not attempt to use opioids while using naltrexone. Although naltrexone blocks the opioid receptor, it is possible to override this blockade with very high doses of opioids. However this is quite dangerous and may lead to opioid overdose, respiratory depression, and death. Similarly one will not show normal response to opioid pain medications when taking naltrexone. In a supervised medical setting pain relief is possible but may require higher than usual doses, and the individual should be closely monitored for respiratory depression. All individuals taking naltrexone are encouraged to keep a card or a note in their wallet in case of an injury or another medical emergency. This is to let medical personnel know that special procedures are required if opiate-based painkillers are to be used.
There has been some controversy regarding the use of opioid-receptor antagonists, such as naltrexone, in the long-term management of opioid dependence due to the effect of these agents in sensitizing the opioid receptors. That is, after therapy, the opioid receptors continue to have increased sensitivity for a period during which the patient is at increased risk of opioid overdose. This effect reinforces the necessity of monitoring of therapy and provision of patient support measures by medical practitioners.
Mechanism of action
Naltrexone and its active metabolite 6-β-naltrexol are competitive antagonists at μ- and κ-opioid receptors, and to a lesser extent at δ-opioid receptors. The plasma half-life of naltrexone is about 4 h, for 6-β-naltrexol 13 h. The blockade of opioid receptors is the basis behind its action in the management of opioid dependence—it reversibly blocks or attenuates the effects of opioids.
Naltrexone's mechanism of action in alcohol dependence is not fully understood, but as an opioid-receptor antagonist is likely to be due to the modulation of the dopaminergic mesolimbic pathway (one of the primary centers for risk-reward analysis in the brain, and a tertiary "pleasure center") which is hypothesized to be a major center of the reward associated with addiction that all major drugs of abuse are believed to activate. Mechanism of action may be antagonism to endogenous opiates such as tetrahydropapaveroline, whose production is augmented in the presence of alcohol.
This article uses material from the Wikipedia article Naltrexone, which is released under the Creative Commons Attribution-Share-Alike License 3.0.