Nalmefene and naltrexone are medications used to treat substance use disorders. Both modulate the brain’s opioid system and are discussed in the context of managing alcohol use disorder (AUD) and opioid use disorder (OUD). They offer different approaches to support recovery.
Naltrexone
Naltrexone functions as a competitive opioid receptor antagonist, binding to opioid receptors in the brain and effectively blocking their activation. This mechanism helps diminish cravings and the rewarding sensations associated with alcohol consumption and opioid use.
This medication is approved for treating both alcohol use disorder and opioid use disorder. For alcohol use disorder, it can be prescribed as an oral tablet, typically taken once daily at a 50 mg dose. For opioid use disorder, an extended-release intramuscular injection, often administered monthly at a 380 mg dose, is available.
Naltrexone helps individuals reduce drinking behaviors and avoid relapses by lessening alcohol cravings. For opioid use disorder, it prevents euphoria and reduces physical dependence, assisting individuals in remaining opioid-free. Common side effects include nausea, headaches, dizziness, fatigue, sleep disturbances, and anxiety.
Nalmefene
Nalmefene modulates the opioid system, acting as an antagonist at mu (µ) and delta (δ) opioid receptors, and a partial agonist at kappa (κ) opioid receptors. This interaction helps regulate the brain’s reward system, reducing alcohol’s pleasurable effects and decreasing cravings.
Nalmefene’s primary approved use is for alcohol use disorder, particularly in Europe where it is marketed as Selincro. It is often prescribed for “as-needed” use to reduce alcohol consumption, rather than for complete abstinence. The recommended dose is 18 mg taken orally, 1-2 hours before anticipated drinking.
Nalmefene has historical use in opioid overdose reversal, though this is not its primary application for AUD or OUD. Common side effects include nausea, dizziness, and insomnia, which often decrease over time.
Comparing Naltrexone and Nalmefene
Naltrexone and nalmefene share the common goal of reducing cravings and consumption in substance use disorders by modulating the opioid system. Both medications affect the brain’s reward pathways to lessen the reinforcing effects of alcohol.
A key difference lies in their precise mechanisms of action; naltrexone is a pure opioid antagonist, fully blocking opioid receptors without activating them. In contrast, nalmefene acts as an antagonist at mu and delta opioid receptors while simultaneously being a partial agonist at kappa opioid receptors.
Pharmacokinetically, nalmefene generally has a longer half-life compared to oral naltrexone, which can influence dosing schedules. Naltrexone has broader approved indications, approved in the US for both AUD and OUD. Nalmefene’s primary approval for AUD is in Europe, where it is often used for “as-needed” reduction of alcohol consumption.
Regarding administration, oral naltrexone is typically taken daily, or as a monthly extended-release injectable for both AUD and OUD. Nalmefene, as an oral tablet, is commonly used “as-needed” before drinking, offering a flexible dosing approach. Side effect profiles for both medications include nausea, headaches, and dizziness. Specific frequencies and severities can vary.
Factors Guiding Treatment Choice
The selection between nalmefene and naltrexone is a personalized decision, made in consultation with a healthcare professional. A primary factor is the specific substance use disorder being addressed. Naltrexone is approved for both alcohol and opioid use disorders, while nalmefene’s primary approved use is for alcohol use disorder, particularly in Europe. A patient’s preference for dosing schedule also plays a role, considering daily oral tablets, monthly injections, or “as-needed” use.
Co-occurring medical conditions and other medications must be reviewed to avoid adverse interactions or contraindications. Naltrexone, for example, is contraindicated if opioids are currently being used due to the risk of precipitating withdrawal symptoms. Geographical availability and regulatory approvals also influence treatment options, as nalmefene is not FDA-approved for alcohol dependence in the US.