• Addiction & recovery

Naltrexone and Naloxone – What’s the Difference?

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David Schwartz, MD

January 10, 2022

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The opioid epidemic is a highly prevalent public health crisis in the United States. Overdose deaths from opioids have been gradually rising for more than a decade, and opioid-related hospitalizations have reached emergency levels. Opioids are prescription medications primarily used to control moderate to severe pain. This large class of medication consists of prescription medications such as morphine, Vicodin, OxyContin, codeine, fentanyl, and illicit substances like heroin. The use of these medications in a problematic pattern that leads to serious impairment or distress is known as opioid use disorder (OUD).

Naloxone and naltrexone are both opioid inhibitors that bind to opioid receptors in the brain to block the effects of other opioids. However, while naltrexone and naloxone may sound and look very similar, the two medications are fundamentally different regarding how they react in the body and the purpose of their use. 

So what’s the key difference between naloxone and naltrexone? Naloxone is an antidote for opioid overdose, while naltrexone is used to manage alcohol use disorder and opioid use disorder by reducing cravings and the risk of relapse.

 

What Is Naloxone?

Naloxone, also known as Narcan, is a medication that rapidly reverses an opioid overdose.  Naloxone is an opioid antagonist (inhibitor) that blocks the effects of opioids by attaching them to opioid receptors in the brain. Naloxone is an antidote that can quickly restore breathing in a person if their breathing has slowed or stopped due to an opioid overdose. 

Naloxone is not a medication for opioid use disorder (MOUD), and it doesn’t work on individuals who don’t have opioids in their system. Naloxone can only be used to counteract the effects of heroin, morphine, and oxycodone. And it doesn’t block substances like alcohol, tranquilizers, cocaine, or amphetamines.

Naloxone can also be found in Suboxone, a medication used in treating OUD, which contains both naloxone and buprenorphine. Naloxone serves as a protective agent against substance misuse in this capacity. 

Naloxone nasal spray is available without a prescription over-the-counter at any pharmacy and is covered by Medicaid, Medicare, and most other commercial insurance plans.

 

What Is Naltrexone?

Naltrexone is a prescription medication that comes as a pill or an extended-release intramuscular injection for treating alcohol use disorder and opioid dependence. The pill form (ReVia and Depade) is prescribed daily, and the extended-release injectable (Vivitrol) is administered once a month by a healthcare practitioner licensed for dispensing medications. Naltrexone helps reduce the risk of relapses as well as cravings and is one of the most commonly used medications in treating alcohol use disorder and opioid dependence.

The injectable form of naltrexone was approved by the U.S. Food and Drug Administration (FDA) for alcohol use disorder (AUD) in 2006 and opioid use disorder in 2010.  Naltrexone is the only medication that isn’t classified as a controlled substance. Naltrexone, like many other medications for opioid use disorder, is most effective when utilized in conjunction with other elements of rehabilitation such as counseling and behavioral therapies.

Naltrexone is generally prescribed after an opioid-free period of seven to 14 days. There are case-by-case-specific circumstances where it can be given in small amounts sooner. However, it can be used by individuals who are currently consuming alcohol. Naltrexone decreases cravings by blocking the effects of alcohol and opioids by binding to the endorphin receptors in the body and blocking opioid receptors in the brain. This function helps maintain abstinence and prolong recovery. Naltrexone’s efficacy in addiction maintenance treatment is due to its non-addictive nature and low potential for misuse.

 

Naloxone Vs. Naltrexone – Administration

Naloxone is available in two forms: nasal spray or auto-injector (in healthcare settings, it can be given Intravenously). The nasal spray is given while the person is lying on their back, and the injection is administered through the thigh. Knowing when to administer naloxone means being able to recognize the symptoms of an impending overdose. According to the National Center for Biotechnology Information (NCBI), the typical symptoms seen in an opioid overdose are pinpointed pupils, respiratory depression, and diminished consciousness. This phase is known as the “opioid overdose triad.” Naloxone is recommended to be administered immediately if a person is experiencing these symptoms. If you don’t have naloxone on hand, seek medical assistance immediately. Most emergency healthcare providers have Narcan on hand to counteract a possibly fatal overdose.

Naltrexone can be prescribed and administered by any healthcare practitioner who is licensed to dispense medications. Clinical studies have demonstrated that 50 mg of naltrexone can block opioid effects for up to 24 hours. The recommended naltrexone dose for AUD is 50 mg (oral tablet daily) and 380 mg (injectable monthly ). And the recommended dose for OUD is 25 mg (oral tablets daily) and 380 mg (injectable monthly). According to the Substance Abuse and Mental Health Services Administration (SAMHSA), the oral tablet is taken daily, and the extended-release injectable formulation is administered once a month.  

 

Naloxone Vs. Naltrexone – Duration of Effects

Naloxone takes less time to start working compared to naltrexone. Naloxone works fast by knocking opioids off brain receptors and reversing the effects of an opioid overdose. The effects of naloxone typically occur within five minutes of administration. The faster the medication is administered, the higher the chances of saving a person’s life.

Even though its chemical structure is similar to naltrexone, naloxone is most commonly used as a short-term opioid blocker. Naloxone is a fast-acting medication that is usually given in a single dose. The medication’s effects usually fade off within 30 minutes and are completely gone after 90 minutes. However, if a person has overdosed on a longer-acting opioid, they may require another dose of naloxone.

Naltrexone, on the other hand, is a slow-acting medication that generally takes effect 30 minutes after its use. The pill form lasts for a day, and the injectable version can last up to 30 days.

 

Naloxone Vs. Naltrexone – Side Effects

Since all chemical substances create alterations in neurotransmitters, hormones, and physiological functions, there are always potential side effects associated with their use. However, the risk of serious side effects from naloxone use is quite low. And the risk of negative effects substantially outweighs the consequences of an overdose. In addition, if the cause of unconsciousness is unknown, administering naloxone is unlikely to cause further harm to the individual. 

Reported side effects of naloxone are often related to acute opioid withdrawal. These may include:

  • Body aches
  • Increased heart rate
  • Irritability
  • Agitation
  • Runny nose
  • Convulsions
  • Vomiting
  • Diarrhea
  • Appetite loss

The most common side effects associated with naltrexone include:

  • Headache
  • Diarrhea
  • Nausea
  • Vomiting
  • Loss of appetite
  • Muscle or joint pain
  • Constipation
  • Dizziness
  • Irritability
  • Nervousness
  • Sleeping troubles
  • Enhanced or decreased energy
  • Abdominal pain
  • Toothache
  • Cold symptoms

Individuals who develop allergic reactions or unusual adverse effects such as chest pains, psychosis, or convulsions should stop using naltrexone and consult their physician immediately.

While naloxone and naltrexone are two very different medications, their effectiveness and their usefulness are undeniable.

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