gabapentin and baclofen overdoses

From: Geoff A. Modest, M.D.
Sent: Tuesday, January 28, 2020 7:45 AM
To: Geoff A. Modest, M.D. <GModest@uphams.org>
Subject: gabapentin and baclofen overdoses

the US Poison Centers have experienced a dramatically increased rate of reports of gabapentin and baclofen exposures (see gabapentin OD clintox2019 in dropbox, or doi.org/10.1080/15563650.2019.1687902) 

Details:
-- retrospective review of the US Poison Centers info (and entered in the National Poison Data System) assessed cases of exposure to gabapentin (2013 to 2017) and baclofen (2014-2017) in those over 18 years old
-- isolated exposures were highlighted in this report, since they included only the single substance involved, and it would be difficult to disentangle the effects of one substance vs its combination with other drugs. Many people, however, do have exposures to multiple substances, and these were reported as the total number of exposures below
--they define “misuse” as intentional improper or incorrect use of a substance for other than the pursuit of a psychotropic effect
--and  “abuse” as substance exposure for intentional  improper or incorrect use where the patient was likely attempting to gain a high, euphoric effect or other psychotropic effect, including recreational use for any effect

Results:
-- gabapentin, from 2013-2017: 74,175 total gabapentin exposures were reported to poison centers, an increase of 72%; 51,932 (70%) were intentional, with 41,948 (81%) of them being attempted suicide, 3537 (7%) abuse exposures, 3639 (7%) as misuse, and 2763 (5%) deemed as intentional exposures but the reason was unknown
    -- isolated exposures: 31% of the total cases, increase of 67% (ie, 69% of exposures were part of polydrug use)
    -- isolated abuse/misuse exposures: 2724 cases (12%), increase of 120%
    -- intentional suspected suicide attempts: 9387 (41%) increase of 81%
    -- the most common co-ingestions: gabapentin with sedative/hypnotic (23%), antidepressants (13%), opioids (9%)
    -- all states found an increase in gabapentin exposures over this time period, 40 states an increase in isolated gabapentin intentional nonsuicidal exposures (highest in Kentucky at 182%, then West Virginia at 141%); the highest relative rate increases were in North Dakota (762%), Iowa (686%) and Maryland (414%)
    -- hospital admissions: of the 22,737 reported isolated exposures between 2013-2017, 17% resulted in admission, of these 54% admitted to critical care units.
    -- Isolated gabapentin exposure was involved in 19 deaths

-- baclofen, from 2014-2017: 15,397 total exposures, a 36% increase; 10,697 (69%) were intentional, 8158 (76%) of these were attempted suicide.
    -- isolated exposures: 6169 (40% of total, and 46% of them were intentional suspected suicide attempts), increase of 35%
    -- isolated abuse/misuse exposures: increase of 32%
    -- intentional suspected suicide attempts: increase of 43%
    -- 43 states had an increase in baclofen exposures from 2014-2017; 33 states an increase in isolated baclofen intentional nonsuicidal exposures, highest in Kentucky, Wisconsin, Virginia, and Missouri (all between 200 to 300%)
    -- hospital admissions: of the 3218 admissions (52% of exposures), 74% require critical care. Death resulted from 18 identified isolated baclofen exposures
-- the most common co-ingested substances included: sedative/hypnotic (22%) opioids (13%) antidepressants (11%)

-- these increases were notable since overall exposures reported to poison centers declined during this time period 
-- all states saw increases in gabapentin exposures, and most state had increases in gabapentin exposures and both gabapentin and baclofen misuse/abuse

Commentary:
-- though the number of opioids being prescribed in the US decreased significantly between 2012 and 2017 (down a bit to a low of 191 million prescriptions, 58.7 prescriptions/100 persons in the US), there has been a dramatic increase in gabapentin and baclofen prescribing (likely in part their being prescribed as adjuvant pain therapies with the intention to decrease opioid prescriptions):

   -- gabapentin:
         -- gabapentin prescribing increased 64%, from 39 million prescriptions in 2012 to 64 million in 2016, the 10th most commonly prescribed medication in the US
        -- gabapentin has been cited for misuse and diversion, with individuals reporting it provided euphoria, relaxation, improved sociability, a marijuana-like ”high”, and a sense of calm; and it has a synergistic effect with opioids
        -- there is no antidote for gabapentin, and overdose therapy may require prolonged intensive management including hemodialysis, because of its long half-life
        -- the blog http://gmodestmedblogs.blogspot.com/2020/01/fda-warning-gabapentinoids-and.html  highlights a recent FDA warning for gabapentinoids and respiratory depression, also citing other blogs suggesting that the clinical benefits of gabapentinoids in pain control are likely small, but the adverse effects quite high 

    -- baclofen:
        -- also a GABA analog, though targeting the GABA-B receptors, and typically prescribed as a muscle relaxant and antispasmodic
        -- baclofen is often prescribed off-label for low back pain (though there is evidence of lots of adverse effects and no significant long-term benefit)
        -- there is significant acute toxicity in those with intentional overdoses, but chronic use induces tolerance, dependence, and a withdrawal syndrome (seizures, agitation, confusion, and delirium)
-- it was notable that the ”overwhelming majority of intentional exposure cases were suicide attempts”

-- Limitations of the study:
    -- this study only included people who accessed the poison centers, so likely significantly underrepresents the full complement of adverse effects of gabapentin and baclofen
    -- there are likely very different reporting ethics in different states, perhaps in part reflecting whether overdoses are rare or common
    -- there were limited granular data on the cases (as would be expected from accumulated registry-type info). but maybe those taking gabapentin or baclofen had more underlying anxiety disorders or other mood disorders, which in and of themselves increase the risk of overdoses/suicide attempts (and taking the gabapentin, for example, was just a side actor???). after all, in the above data, lots of the calls to poison centers were for likely suicide attempts. and if people did not have access to gabapentin/baclofen, these individuals might have resorted to a worse drug (eg acetaminophen)???
    -- though it makes sense to look at people exposed to just these meds, some of the adverse effects of polydrug use may well have been from the gabapentin/baclofen components. and there also may well be synergy between gabapentin/baclofen and the other drugs taken (ie, it may be that the other drugs would not have been so dire by themselves, but the synergy with gabapentin/baclofen caused the problem)

--this blog complements a recent one finding that closing automobile factories is associated with increased opioid mortality, see http://gmodestmedblogs.blogspot.com/2020/01/opioid-od-mortality-increased-with-auto.html

so, yet another warning about prescribing gabapentin as a pain control adjunct, this time highlighting baclofen as well. Though baclofen is a minor actor vs gabapentin, it actually seems to be more toxic, with higher relative risk of serious morbidity and mortality.   it is likely that part of the increased misuse of gabapentin/baclofen is related to clinicians prescribing these meds as adjuncts for pain control, as an attempt to decrease opioid prescribing. but as mentioned above, it is really not clear that gabapentin/baclofen have any significant real clinical indication for pain control, and they do have significant toxicities alone.  And, in the majority of cases, these drugs are taken as cocktails with many other potentially hazardous substances, especially sedatives.

I will follow this blog soon with a couple of blogs highlighting some new articles on nonpharmacologic approaches to pain management, and include links there with prior blogs about other nonpharmacologic therapies found to be effective. And, I think, these nonpharmacologic approaches really need to be pushed more strongly by us clinicians as a first line approach to avoiding or decreasing other medications…

geoff​

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