2 blogs in 1 -- kratom, and repeated opioid overdoses

a couple of recent articles relating to opioid dependence.

1.the NY Times had an article on kratom, a natural product sometimes used for opiate withdrawal but  is itself addictive (see http://www.nytimes.com/2016/01/03/us/kratom-an-addicts-alternative-is-found-to-be-addictive-itself.html?emc=edit_th_20160103&nl=todaysheadlines&nlid=67866768&_r=0 ​). a few points from the article:

--they highlight a few cases of individuals trying to recover from heroin addictions by taking kratom, which relieved the withdrawal symptoms but led to addiction to kratom, with cravings, taking increasing quantities over time, and severe withdrawal symptoms. and there is a "large epidemic in Florida"

--kratom is natural plant (mitragyna speciosa, a tropical deciduous and evergreen tree which reaches up to 30 ft tall, from Southeast Asia, esp from Indochina and Malaysia), marketed as a "natural painkiller". it functions as a mu-opioid receptor agonist. and its metabolites are NOT DETECTED on using drug screening. it was first used in Southeast Asia as a substitute for opium when that was not available, and is typically ingested by chewing the raw leaf. [also used by laborers to give energy and as mood enhancer/painkiller (sounds like cocaine use by field workers???, though this was not in the article]

--and, of course, the FDA cannot regulate it since it is a "dietary supplement". though in 2014 the FDA  did ban the import and seized a shipment of 25,000  pounds in Los Angeles. However, it is just a "drug of concern" for the FDA and not a controlled substance. it is also making its way into the country with the label "not for human consumption", and non-alcoholic bars sell kratom as a drink, often without it being explicitly on the menu, with the article noting bars in colorado, new york and north carolina, "as well as other states"​

a brief internet review by me shows many, many suppliers of kratom, with many different strains/names of kratom products, provided as a powder/leaf/extract/tea bags /capsules, and costs about $10-16/ounce. with free shipping and discounts on higher quantities ($220/pound)... Though it is illegal to ship to a few states (indiana, tennessee, vermont, wyoming). it is still more expensive than street opium, leading some to revert to heroin. And, there is even an American Kratom Association...

2. The annals of internal med article looked at patients with nonfatal opioid overdoses (ODs), the rate of subsequent opioid prescriptions, and the rate of repeated overdoses (see opioid OD and repeated scripts ODs AIM2015 in dropbox or doi:10.7326/M15-0038). details:

--they accessed the Optum database, a complete inpatient, outpatient, and pharmacy claims database from all 50 US states, which included 50 million commercially enrolled patients from 2000-2012

--2848 noncancer patients who had nonfatal OD on initial presentation (mean age 44, 40% male, daily opioid dose of <50mg/d MED in 33%/ 50-100 mg in 22%/ >100 mg in 46%, mean daily MED was 152-164 MED/ peaking at 187 on the day before OD, 56% were on benzos in past 90 days, 59% with "mental health diagnosis" within 90 days of OD, 88% on opioids for extremity pain/with an array of other painful sites, 51% from the south/24% midwest/20% west/6% east). [MED=morphine-equivalent dose]

--patients were followed from 90 days prior to initial OD until either: a second OD event, disenrollment from plan, age >65 (medicare eligible), 2 years after initial OD.

--results:

    --mean followup of 299 days

    --30 days after the initial OD, the mean MED dose decreased to 118 mg/d, and remained in the 111-131 range over the 2 years of followup

    --in the followup period, 2597 patients (91%) received 1 or more opioid prescriptions

        --on days 31-60 after OD, 70% were on active opioid prescriptions on any given day, which trended down to 64% at the end of the 2 years

        --opioid discontinuation after the OD was in 10% on the highest MED doses, 15% in the moderate dose group and 14% in lowest dose group

        --patients largely stayed in the same opioid dose category from before to after the initial OD, with 31-36% being in the high dose group

    --a primary care provider was identified in 76% of the patients, and in 61% it was the same person before and after the OD. 30% of patients switched to a new provider after the OD.

    --in the post-OD period:

        --58% got some benzos, and in those with active benzo prescribing this was more common in those who continued getting opioids

        --7% got buprenorphine

        --75 (n=212) had a repeated OD, which was highest in the group on large dose opioids (17%), less so with moderate dose (15%) , and no clear difference between those on low-dose and not on any (9% and 8%). these translate into HRs (vs not getting subsequent opiods):

            --low-dose, 1.13 (0.69-1.85), non-significant

            --moderate dose, 1.89 (1.18-3.04), ie an 89% increase

            --high dose, 2.57 (1.72-3.85), ie a 157% increase

            ​--and, overall in those with active benzo prescribing, 1.74 (1.31-2.32), a 74% increase

        ​--subsequent medical claims for drug withdrawal treatment (n=267, 9%) were highest in those on large doses opioids, lowest in moderate, and in-between for low or none.

so, these articles bring up several issues:

--we as providers should be aware of the kratom issue, since this appears to be an addictive opioid, readily available, not-so-expensive, which does not show up on our usual tox screens. and the substance is a dietary supplement, not monitored by anyone (eg FDA) for quality, consistency of preparation etc and could easily have added drugs (fentanyl??, others??) and variable potencies and the potential for increasing concerns about addiction and ODs

--the second article raises lots of issues. clearly there is an inherent issue of OD with patients who are on opioids, and these may well be higher in those with "mental health diagnoses", on benzos or on higher opioid doses (and, by the way, may be higher in those in chronic pain anyway). but other issues of concern include:

    --the remarkable lack of a coherent system of health care in the US, with general lack of communication between providers. it is not clear from this retrospective database scouring how many patients had a primary care provider (which i would imagine is more than the 76% of claims which documented one, since these patients did receive regular prescriptions for the opioids), or how many of the primary care providers even knew about the OD happening (which certainly places the patient at a higher risk of a subsequent OD).

    --and, yet again, the bottom line issue remains of how to treat patients with chronic pain who only get relief from opioids, in an environment where we as health care providers do not have adequate clinical studies assessing the actual benefit vs risks of opioids and especially at higher doses (for an array of my past blogs and comments on this issue see http://gmodestmedblogs.blogspot.com/search/label/pain%2Fopiates  ).

    --and, it is easy to look at these studies such as above and conclude that opioids are "not safe", or that we should just follow the recommendations of the CDC or other organizations (by the way, the recent CDC guidelines were retracted because of public outcry about the lack of studies -- see above link for review of the guidelines).

    --but it is really different as a primary care provider who has a patient in front of him/her who has disabling chronic pain and is not able to function even close to normally, who seems to get great relief from opioids in terms to returning to a much more functional state, who may even need high MED dosages to get that response, and who is willing to take the risks of adverse outcomes to maintain this functionality (and we do give out lots of other drugs which potentially – and actually – cause very serious harms, where it seems that the benefits warrant prescribing them).  i think that this brings up another issue about recommendations overall -- they tend to be formulated by researchers in the field who are somewhat removed from the day-to-day practice of us guys in primary care, and it is pretty easy to make recommendations which are not so relevant to taking care of actual patients (ie, making recommendations from aggregate data and "expert opinion" may not be particularly helpful in figuring out what to do with the patient in front of you. especially if these recommendations do not reflect real practice situations but come from heads of specialty groups who in fact have not a lot of real patient experience).

    --that all being said, there are no doubt safety issues with opioids. we need to explore all avenues to avoid or minimize their use (ancillary therapies, meds, etc), we should identify those at highest risk of harm and make sure they are plugged into appropriate programs to minimize that risk (eg, it seems reasonable to me to require those with psych issues to be in counseling or medical treatment for these issues), and we really need an overall system which allows for easy, pretty seamless flow of information between providers and one not limited by needing the same electronic medical record in all institutions.