Law of Unintended Consequences:  Gabapentin Meets the Opioid Crisis

By: Mario Ramirez, MD

Reading Time: 4 minutes

Gabapentin pill packs, the opioid and chronic pain crises in the United States, many of us on the front lines of clinical and research medicine have been searching for opioid alternatives that we can safely use to manage our patients’ pain. 

We have previously covered the National Institute for Health (NIH) research initiatives to identify opioid alternatives to produce the next generation of pain medications that won’t have the addictive qualities of opioids. But until that research produces viable alternatives—a process that could take years if not decades—many of us are prescribing opioids in lower amounts.

That has, in turn, increased the need for adjunct, non-narcotic medications from other drug classes including gabapentin, amitriptyline, and ketamine, among others.  While this practice may decrease the total number of morphine equivalents being prescribed across the country, the law of unintended consequences suggests that there will be follow on problems that are unexpected. 

Just last month, NBC News published a story about gabapentin as a potential next wave in the drug epidemic facing our country.  While gabapentin is thought to be non-addictive and relatively safe in isolation, several studies have now shown that it can act as a potentiator for opioid medications and increase the risk of fatal overdose—in essence, a user can take an opioid together with gabapentin and experience greater euphoria. The mechanism for this potentiating effect is still being worked out, but it appears that it increases activation of the opioid receptor which then leads to increased respiratory depression and subsequent overdose. (CMS recently included the drug in its list of potentiators as a part of the group's recent opioid prescribing guidelines.)

Even more concerning, in patients on Suboxone for drug addiction, it can paradoxically block naloxone’s activity at the opioid receptor which then allows the buprenorphine to cause an unintended high.  In drug monitoring programs that are not testing for the presence of gabapentin—which is not a routine screen—participants can have a completely clean drug screen and still be abusing buprenorphine. 

Starting in 2016, public health officials in Kentucky began to pick up on the issue when they noted that gabapentin was present upon autopsy in up to a third of the overdose fatalities.  Several other states also noticed that the number and frequency of refills for gabapentin were increasing dramatically.  As a result, this led officials in some states to begin classifying gabapentin as a Schedule 5 drug meaning that it would get reported to state controlled substance databases.  But, because it is not a controlled substance registered with the U.S. Drug Enforcement Agency, we have inadvertently created a significant problem.  Gabapentin is now a medication that is: a. recommended by the CDC as a nonopioid painkiller; b. known to increase the risk of fatal opioid overdose; and c. monitored by some but not every state as a scheduled drug.  It’s no wonder that it has become increasingly frustrating and unsafe for physicians to adequately address our patients’ pain.

Gabapentin can be a very useful drug.  The point here is not to malign it and say that it has no use.  It absolutely does.  But, I suspect that this link between this drug and fatal opioid overdoses will not be the last we learn about.  As we increase the use of non-opioid adjuncts in pain management, it is critical for clinicians to monitor the resulting trends in public health.  Unfortunately, despite our best efforts, this opioid crisis is not going to go away any time soon.

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