Naltrexone

Naltrexone is completely different than methadone or buprenorphine; it is a complete antagonist at the mu receptor. Think of it as extended-release naloxone. While there is an oral form, almost all patients will be on the injectable form, which is meant to last a month to help with compliance. With its high binding affinity to the mu receptor, it works by preventing patients from getting high if they try to use while on the medication. There is no euphoria associated with it, and at least initially, it won’t help with cravings.

Patients must abstain from all opioids for at least seven to 10 days prior to receiving naltrexone. If they do not, the drug can precipitate severe opioid withdrawal. Unlike naloxone, which should improve after 40 to 60 minutes, or buprenorphine, which can be overcome by giving more buprenorphine, this effect of naltrexone can last a long time. Remember the injectable form can last 30 days, but the withdrawal should not last nearly this long.

While precipitated withdrawal is the main complication we worry about with naltrexone, there are also reports of agitated delirium following the administration of it in patients who recently used an opioid.^10,11 Otherwise, it is very safe unless patients try to overcome the blockade with either very large doses or very potent opioids, or they relapse but now have very little tolerance.

It’s important to mention that there are other indications for naltrexone. It is used in patients with alcohol use disorder due to the effects of mu receptors on our reward system. There is also a weight-loss pill that is a combination of bupropion and naltrexone. This isn’t a huge problem, unless someone doesn’t obtain a complete history and prescribes it to an opioid-dependent patient. We’ve had at least one patient to whom this happened, and it took large amounts of fentanyl and multiple antiemetics to improve her symptoms. We’ve also recently noticed a few physicians using low-dose naltrexone for chronic pain.^12,13

What About Lofexidine?

You may have also heard of a new, recently approved drug indicated for opioid withdrawal, lofexidine. It’s actually been used in Europe for years. Alas, it is just an α-2 agonist, very similar to (and much more expensive than) clonidine. It is not used for MAT.