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Pain/opiates

Primary Care Corner with Geoffrey Modest MD: Decreasing opiate prescriptions

19 Jul, 17 | by gmodest

by Dr Geoffrey Modest

 

Some (likely) good news about prescription opioids from the CDC (see https://www.cdc.gov/mmwr/volumes/66/wr/mm6626a4.htm?s_cid=mm6626a4_w ).

 

— Opioid prescribing in the United States between 2006 and 2015 peaked in 2010 at 782 morphine milligrams equivalents (MME) per capita then decreased annually to 640 MME per capita in 2015

— there was pretty striking variation by US county, from 203 MME in the lowest quartile to 1319 MME in the highest; multivariate adjustment for many risk factors for opiate prescribing (more non-Hispanic white population, higher rates of uninsured and Medicaid, lower educational level, higher unemployment, living outside the urban areas, more dentists and physicians per capita, more diabetes/arthritis/disability, higher suicide rates) only accounted for 32% of the variation in prescribing [ie, there was much more to it than the expected risk factors… ?perhaps issues like the specific medical cultures in the different areas? other major differences in accident rates, which might reflect very different occupational exposures in different areas??….]

— Prescription rates also increased from 72.4 to 81.2 prescriptions per 100 persons between 2006 and 2010, then declined to 70.6 per 100 persons from 2012 to 2015, a 13.1% decrease.

— High-dose opioid prescribing (daily dose of >90 MME) has decreased much more dramatically: 11.4 per 100 persons in 2010, then 6.7 per 100 persons in 2015.

— The average days supplied of opiates increased 33.0% from 13.3 in 2006 to 17.7 in 2015 [presumably from decreased prescriptions for shorter term opiate prescriptions].

Commentary:

— the situation is still dire: opioid-related deaths from overdoses continues to increase, with 33,091 deaths in 2015, approximately half involving prescription opioids, though a good part of this problem is from heroin laced with fentanyl or other very high potency derivatives.

— Approximately 2 million individuals in the United States have opioid use disorder associated with prescription opioids, with an estimated economic cost of $78.5 billion

— though the opioid prescription rate has decreased since 2012, it still is three times higher than in 1999 (180 MME per capita) and is four times higher than in Europe in 2015.

— It is likely that the decreased prescriptions for opiates of late is related to increased awareness among clinicians, policies implemented by states to decrease opioid prescriptions, use of prescription monitoring programs, and other local efforts. An initial concern, which has not borne out, was that decreasing prescription opioids would lead to more use of more dangerous illicit drugs. However it does seem that these more restrictive policies have decreased the amount of opioids prescribed, prescription opioid involved overdose deaths, and also all opioid involved deaths (see Dowell, D. Health Affair (Millwood). 2016, 35(10):1876).

— but, unfortunately, such data do not take into account the other half of the picture: what is the effect of lower prescription rates on patient outcomes?? are more patients functionally impaired or incapacitated by lower doses of opiates? are fewer patients able to work or lead productive lives? what are the effects on their families? their communities?

 

So,

— as most of us in clinical practice know, is usually very difficult to convince patients already on chronic prescription opioids to stop taking them entirely, let alone decrease the dose significantly; patients often state that they need these meds to function. So, in many ways, the biggest long-term solution really is to dramatically decrease the number of new patients who are put on opiates. This involves a concerted effort by surgeons to avoid automatically prescribing opiates for surgery/pain (some patients do fine on non-opiates, with studies suggesting for example equal efficacy of NSAIDs for renal colic), emergency rooms to significantly decrease opiate prescriptions (which often make it very hard for us in primary care to stop prescribing them), as well as us in primary care avoiding using opiates whenever possible. There are many non-opiate approaches, medical and psychological (e.g. cognitive behavioral therapy, yoga, etc.) which may do well (see below). And, at least my experience in Boston is that many clinicians are prescribing opiates much less readily than previously.

— As mentioned in prior blogs (see below), once giving opiates to both young people and elderly seems to lead to more likelihood of continued opiate use/prescription subsequently.

— So, to me it is quite impressive that over the last five years there is been such a significant decrease in overall opiate prescriptions, but especially in those on higher doses (which may be associated with increased mortality), the apparent number of short-term prescriptions, as well as the increased documentation of nonopiate approaches which seem to help.​ But i am still concerned that at least some patients are now being undertreated for their pain….

 

See:

blog of study which found benefit for cognitive behavioral therapy for low back pain

blog of study finding pain control for knee pain through an internet-based home program

blog of a study showing that in older patients, those prescribed opiates for similar conditions were more likely to continue on opiates later

blog of a study finding that teens at low risk of illicit drug dependence who were given legitimate prescription opiates as 12th graders were 3-fold more likely to have opiate use disorder at age 23

Primary Care Corner with Geoffrey Modest MD: Benzos may not increase mortality risk

17 Jul, 17 | by gmodest

by Dr Geoffrey Modest

​ The BMJ just had an article assessing mortality from benzodiazepines from a large US commercial healthcare database, showing minimal increased mortality risk (see doi.org/10.1136/bmj.j2941).

Details:

— 1,252,988 randomly selected patients, comparing those initiated on a benzodiazepine during a medical visit within the prior 14 days vs 1,252,988 non-initiators, from 2004-2013

— all patients were required to fill at least one prescription for any medication both in the 90 days and 91- 180 days before the index date (ie, they were plugged into medical care and filling prescriptions), and high dimensional propensity scoring was done (see below).

— Mean age 46, 85% men, mean Charlson comorbidities score 0.5 (ie, low), 5% smokers, 4% obesity/overweight, 28% hypertension, 1% heart failure, 5% ischemic heart disease, 25% hyperlipidemia, 10% diabetes, 3% COPD, 5% asthma, 10% neuropathic pain, 20% back pain, 3% kidney disease, 10% cancer, 10% anxiety, 10% sleep disorder, 11% depression, 2% drug or alcohol misuse [reaffirming that this is a pretty healthy and younger population overall]

— Medications included SSRIs in 18%, opioids in 30%, barbiturates in 2%, antipsychotics in 2%, other anxiolytics in 1%

— of note, in comparing benzodiazepine initiators vs non-initiators, prior to propensity scoring, the benzodiazepine group had more smokers, hypertensives, atherosclerotic disease, hyperlipidemia, COPD/asthma, neuropathic pain, cancer, a lot more anxiety and depression, and were much more likely to be on beta blockers, steroids, opioids (35% vs 24%!!), anticonvulsants, SSRIs (22 vs 12%), and other hypnotics. All of these characteristics were well-balanced after propensity score matching

— Short acting benzodiazepines were more frequently prescribed, 75% of the filled prescriptions, and alprazolam was the most commonly prescribed of them (47.2%), and diazepam was the most commonly prescribed long-acting agent (87.8%). On review of their supplementary materials, they did include clonazepam as a short acting benzodiazepine, though it’s half-life is actually quite similar to that of diazepam  (both about 20 hours, sometimes much more: >60 hours)​. Not sure why they did that.

— main outcome: all-cause mortality, as determined by linking to the Social Security Administration Death Master File. The overall mean follow-up was 159 days for the benzodiazepine initiators and 146 days for the non-initiators.

— secondary analysis: comparing mortality in patients initiating benzodiazepines with other active treatments (i.e. SSRI antidepressants), also with high dimensional propensity score matching

 

Results:

— over 6 months of follow-up, there were 12.2 events per 1000 person-years in the benzodiazepine initiators vs 6.9 events per 1000 person-years non-initiators, a 78% increased mortality risk. But, given the different baseline characteristics of these groups, probably  the most relevant finding was that after the high dimensional propensity scoring, there were 5061 deaths in benzodiazepine initiators vs 4,691 in non-initiators, 9.3 vs 9.4 events per 1000 person-years; HR 1.00 (0.96 1.04 ). ie no difference

— a 4% increased mortality risk was observed in those on benzodiazepines when the observation period was extended to 12 and 48 months of follow-up.

— benzodiazepines were associated with a 9% increased risk as compared to those starting SSRIs

— in subgroup analysis, older patients initiating benzodiazepines with a longer half-life had no increased risk of all-cause mortality, however younger patients and patients using the short-acting benzodiazepines did have a 9% increased risk.

Commentary:

— Propensity match scoring was used to mathematically control for potential measured confounders. The high dimensional propensity score algorithm also used above is an automated technique which prioritizes/controls for more than 300 covariates that may serve as proxies for unmeasured confounders in large electronic databases. but it is important to reinforce that even large observational studies as this one do not enable us to draw definitive conclusions about causality: there still could be unmeasured variables which are primarily responsible for any associations. This population overall was pretty healthy, those on benzodiazepines less so, emphasizing that there might well have been other significant differences between these groups (though the lack of association is reassuring, since these sicker patients, controlling for their measured sicknesses but were probably at higher risk for other unidentified sicknesses and more likely to have a less healthy lifestyle, and they did not have higher mortality than the much less sick non-benzo initiators).

— As we know, benzodiazepines are frequently used in the outpatient setting, in 2008 approximately 5.2% of US adults aged 18 to 80 used benzodiazepines, increasing from 4.1% in 1996 to 5.6% in 2013. Similar numbers were found in British Columbia, Canada. Use increases with age, with a higher usage in those older than 50, especially for anxiety and sleep disorders. The concerns about their use in the elderly is related to prior reports of a threefold or more increased risk of all-cause mortality, even for short duration usage. And concerns remain about increased falls and fractures in the elderly. it should also be emphasized that this population above is a younger one, a selection bias related to the fact that this was a commercial healthcare database.

— It seems pretty remarkable that in the overall population, 35% of those who initiated benzodiazepines were on opioids vs 24% who did not start benzodiazepines. Given the apparent higher mortality of benzodiazepines in those on opioids found in a few observational studies (eg, see blog), it would have been useful to know specifically how the opioid subgroup fared. One concern that I have regarding the potentially increased mortality of combination of benzodiazepines and opioids is whether it is really from the combination or from the patient mortality associated with the conditions that the benzodiazepines might be treating (e.g. the significantly increased mortality of panic or other anxiety disorders).

So,

—  the increases in mortality found in the subgroup analyses above were very small, though statistically significant because of the huge number of patients evaluated​. so, clinically they found essentially no difference in those initiating benzos

— from a clinical practice perspective, this study to me is largely reassuring​: I have certainly seen many older patients (again, not well represented above) who are severely functionally affected by anxiety, resistant to non-pharmacologic therapies as well as non-benzodiazepine drugs. I have prescribed benzodiazepines in many if them with excellent results. Preferentially I have used longer acting benzodiazepines, such as clonazepam (though as noted, they consider this a short acting benzodiazepine in the above study, but i think that might be an erratum), even in patients in their 90s. Patients certainly understand the potential increased risks of falls and possible increased mortality, but are desperate for immediate symptomatic relief.

Primary Care Corner with Geoffrey Modest MD: Low use of buprenorphine in youth

22 Jun, 17 | by gmodest

by Dr Geoffrey Modest

A recent large-scale analysis from health insurance claims found that under one-quarter of adolescents and young adults with opioid use disorder (OUD) received either buprenorphine or naltrexone (see doi:10.1001/jamapediatrics.2017.0745)

 

Details:

— retrospective cohort study based on reviewed insurance claims of 9.7 million youth aged 13 to 25; they identified 20,822 with a diagnosis of OUD 2001 to 2014, and matched them with those receiving prescriptions for either buprenorphine or naltrexone within 6 months of the OUD diagnosis. They used the national commercial insurance database Optum, which has inpatient, outpatient, emergency dept and pharmacy claims from large commercial health insurer databases, with members in all 50 states.

— In those with OUD: 66% male, 82% non-Hispanic white/6% Hispanic/2% non-Hispanic black or Asian, mean age 21 at 1st diagnosis, 68% urban, neighborhood educational level was rated high 67%/high-middle 20%/low-middle 10%/low 3%, neighborhood poverty level was rated high 6%/high-middle 15%/low-middle 25%/low 54%, region South 42%/Midwest 26%/West 17%/Northeast 15%

— diagnosis of OUD: 3% age 13 to 15/9% age 16 to 17/35% age 18 to 20/53% age 21 to 25

 

Results:

— the rate of OUD diagnoses increased from 0.26/100,000 person-years in 2001 to 1.51/100,000 person-years in 2014, a 6-fold increase

— overall, 26.8% of the youth were dispensed buprenorphine/naltrexone within 6 months of OUD diagnosis, with 89% being buprenorphine and 11% naltrexone (the relative use of naltrexone has increased in the last 5 years)

— medication prescriptions increased from 3% in 2002 (year buprenorphine introduced) to 31.8% in 2009, then decreased to 27.5% in 2014;

— in multivariable analysis (controlling for sex, age at OUD diagnosis, race/ethnicity, geographical region, neighborhood educational level and neighborhood poverty level), adjusted probability of receiving buprenorphine/naltrexone:

— age 13 to 15: 1.4%

— age 16 to 17: 9.7%

— age 18 to 20: 22%

— age 21 to 25: 30.5%

— the above trend had p<0.001 for the difference

— females: 20% vs 24% of males (p<0.001)

— 14.8% non-Hispanic black vs 20% Hispanic vs 23.1 % non-Hispanic white (p<0.001)

​–so, lower likelihood of treatment in younger people, females, non-Hispanic black or Hispanic youth

 

Commentary:

— we are all aware of the huge medical and social issues associated with OUD, including mortality (now surpassing that of motor vehicle accidents), diseases (increases in hepatitis C, HIV), mortality, costs to the system (ER and hospital use) and huge social disruptions

a prior blog highlighted the tripling of opioid deaths from 1999 to 2014

and another blog specifically reported youth substance use and trends in 2013

— as noted in the current article, prior studies have found that 2/3 of people in treatment for OUD began drugs before age 25, and 1/3 before age 18, though only 1 in 12 adolescents and young adults are in treatment

— there have been some important deficiencies in the approach within pediatrics: the American Academy of Pediatrics did not come out with a policy statement recommending the use of pharmacotherapy for OUD until August 2016, though buprenorphine was approved for those >15yo in 2003; and only 1% of the physicians certified to prescribe buprenorphine are pediatricians

— one striking incongruity is the rather unfortunate situation where clinicians can prescribe opiates without specific training, yet they need formal training to prescribe the safest opiate, buprenorphine, one that has a pretty remarkable track record in helping people with OUD

— there was an interesting discordance in the above study between the neighborhood educational level, with 87% being high or high-middle, though poverty levels was only 21% in the high or high-middle range. Not sure what to make of that, though it should be noted that these data were from geographical tracks and not granular data from individuals with OUD. Also the race/ethnicity of the patients is based on the neighborhood characteristics and surname analysis, without the actual patients’ data

— this study only looked at young patients using buprenorphine or naltrexone within 6 months of their initial encounter for OUD. There are some unanswered questions (at least to me) which make it hard to put this in perspective: though only 1/4 of the youth were on these meds at 6 months, how many older patients are on the meds within 6 months of diagnosis??? (I certainly see many adults you do not get into treatment for decades, and then do really well….)  It may well be that the youth with OUD are not ready to get off the opiates that soon after starting. It would be interesting to look at the number in treatment after 1 or more years after starting.

–it is a bit unnerving that the total proportion of youth dispensed buprenorphine/naltrexone peaked in 2009 (32%) and has trended a bit down since (to 28%), given the increasing mortality from opiates, despite the increased numbers of insured people under the Affordable Care Act (which unfortunately may change soon)

— a prior blog reviewed data showing that even appropriate use of prescription opiates in teens is strongly associated with future opioid misuse, even among teens with low pre-opioid likelihood of developing OUD, see   (ie, opioids even given after surgery in younger people seems to create the increased likelihood of OUD later in life)

the blog raises concerns about naltrexone, given the very limited studies on it. The blog also comments on how the drug company is aggressively lobbying congress and specifically the trump administration to promote naltrexone, despite this paucity of scientific evidence (which the drug company seems not to be interested in pursuing)

 

so,

–this article highlights both this dramatic 6-fold increase in documented OUD in youth over the past 15 years (part of which may be our heightened awareness of the issue, but it is pretty clear that things are a whole lot worse), as well as the fact that such a small percentage of youth are involved in treatment.

— but, I think part of the issue is national stigmatization of those with OUD, which may be responsible at least in part for requiring clinicians to have special training/licenses to prescribe buprenorphine (as opposed to naltrexone), despite its documented safety and effectiveness. This problem with buprenorphine is likely to be exacerbated by tom price, the head of Dept of Health and Human Services in the US, who is pushing for naltrexone, as noted in above blog. Removing constraints on prescribing buprenorphine would not only further legitimize its use but also make it much more available to patients in need

–and part of the problem is our medical culture, which abetted and fueled the current opioid crisis by pushing more aggressive treatment of pain in the 1990s (and this was fed into/strongly promoted by industry, and specifically Purdue, maker of oxycontin, and pusher of “pain as the fifth vital sign”). Yet now one area of the medical culture has played a role in minimizing aggressive OUD treatment (eg, the Am Acad of Pediatrics, not dealing with OUD for more than a 14 years after buprenoprphine became available despite the well-documented dramatic increases in opioid use in youth and its huge social/medical consequences).

 

Primary Care Corner with Geoffrey Modest MD: Opioidsx3, and drug company shenanigans to boot

13 Jun, 17 | by gmodest

by Dr Geoffrey Modest

This is a triple blog on a few recent developments in the opioid world.

  1. The FDA just announced that they are seeking removal of Opana ER, long-acting oxymorphone hydrochloride, “based on its concern that the benefits of the drug may no longer outweigh its risks”. [And certainly many of us thought it was ridiculous to approve it from the start. We have all been through this scene before with oxycontin…].  The FDA found (not so surprisingly) that there was a shift in its route of abuse from nasal to injection after the product was reformulated (it had been reformulated “to make it more resistant to physical and chemical manipulation for abuse by snorting or injecting”….).   This increase in injection use has been associated with outbreaks of HIV, hepatitis C and some cases of thrombotic microangiopathy. And if the company refuses to remove the drug from the market voluntarily, the FDA will formally require its removal by withdrawing its approval. (see see https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm562401.htm​  )

 

  1. the NY Times had an article on 6/10/17 highlighting the increasing role of the internet in buying opiates (they highlight fentanyl), using the “dark web sites” whereby the drugs can be bought anonymously using a special browser, buying the drugs with virtual (untrackable) currencies like bitcoin. A couple of 13-year olds were also highlighted, who had gotten the drugs this way. The reporter commented that “the leading dark net market, AlphaBay, had >21,000 listing for opioids and >4100 for fentanyl and similar drugs from dozens of dealers large and small”. see https://www.nytimes.com/2017/06/10/business/dealbook/opioid-dark-web-drug-overdose.html ​

 

  1. another NY Times article on vivitrol (extended-release injectable naltrexone), suggested lots of drug company shenanigans (see https://www.nytimes.com/2017/06/11/health/vivitrol-drug-opioid-addiction.html ). Basically,

–it is being marketed very aggressively (billboards, buses, subways)

–there are no head-to-head studies with buprenorphine to show its relative effectiveness (and the company seems to not have the least interest in doing those studies)

–it is more expensive than suboxone (eg, 3-fold) [though I should add that naltrexone is an old generic drug, used in the past with some limited success for alcohol dependence, reformulated as an extended release injection but with a dramatic increase in cost]

​–the studies supporting its use are weak: eg a Russian study of 250 patients, where 1/2 failed to stay abstinent for 6 months, though it was better than placebo. And this study and another had very high dropout rates (50% range)

–the new head of Health and Human services, tom price, “ignored widely accepted science” and is praising vivitrol as “the future of opioid treatment”, since the other meds (methadone and buprenorphine​, which work really well) simply “substitute for illicit drugs”

–not shockingly, the drug company Alkermes has been spending millions of dollars in contributions to officials involved in dealing with the opioid crisis (primarily spending money on them vs the usual: doctors and medical associations). it spend $19 million on federal lobbying since the drug was approved in 2010, and $222,521 in political contributions to congress last year

–the company even provides free shots to inmates, with the hope that they will continue to get them when out of jail (??getting people hooked on vivitrol??). And, this has worked pretty well: sales of $58.5M in first quarter in 2017, up 33%, 1/2 from Medicaid, and with huge expansion of Medicaid coverage for it (was 15 programs in 2012 in 9 states, now 450 programs in 39 states).

–and, this promotion of vivitrol may be very harmful: in the setting of the ongoing opioid crisis, and trump’s plan to spend $1 billion for new addiction and treatment programs over the next 2 years, trump and price could really undercut very effective treatments for a largely untested one that appeals more to them, perhaps both financially and ideologically (ie, a lock-step response of “just say no to opioids” without looking at the science or studies)….

 

so,

–it is consistently scary how our system works, in this case likely from greasing the palms of the officials. And it really could lead to vivitrol leapfrogging above buprenorphine or methadone in our political climate. i (and everyone else i know) are generally really impressed with the effectiveness of buprenorphine, including in its long-term use in patients. and it is so safe, as compared to other opiates (and most other meds….).

–getting rid of Opana ER, which many states in the US attempted initially but unsuccessfully​ to block, is a feather in the cap of FDA (it had seemed unlikely that the current FDA leadership would take such a strong position)

–the issue of the dark web is truly scary by making these drugs so much easier to access and so anonymously (eg by kids sitting at home but with internet access).

Primary Care Corner with Geoffrey Modest MD: Home-based CBT for low back pain

6 Apr, 17 | by gmodest

​by Dr Geoffrey Modest

 

As mentioned in a recent blog (see here ), the effectiveness of medications for chronic pain is somewhat limited, and more studies have been coming out about nonpharmacologic therapy, either as solo or adjunctive therapy. Cognitive behavioral therapy (CBT) has been shown to benefit patients with chronic low back pain (see blog referenced below), but patient access to such therapy may be limited. In this light, a new trial showed that home-based, telephonic therapy may be as good as in-person CBT (see doi:10.1001/jamainternmed.2017.0223).

 

— Details:

— a single center VA study enrolled 125 patients with chronic back pain, allocated equally to interactive voice response-based CBT (IVR-CBT) versus standard CBT

— this was a non-inferiority study, with primary outcome being change from baseline to 3 months in patient-reported Numeric Rating Scale (NRS) of pain, a scale from 0 to 10. Secondary outcomes included pain-related interference in daily activities; and emotional functioning, sleep quality, and quality of life at 3, 6, and 9 months. These were assessed by the West Haven-Yale Multidimensional Pain Inventory, and the Morris Disability Questionnaire.

— 97 men and 28 women, 65% white/26% black, mean age 60, 20% full-time employed/14% part-time/15% unemployed/29% retired, 18% disabled, 26% with history of substance abuse, mean duration of back pain was 11 years, 55% with nonspecific cause/43% with radiculopathy or spinal stenosis, 12% with opioid prescriptions at baseline, average NRS pain rating was 5.58,

— All patients received a manual specific to their intervention (CBT versus IVR-CBT), to be followed over 10 weeks. The manual included an introductory module about the rationale for CBT, 8 pain-coping skill modules, and a relapse prevention module. All patients received IVR, consisting of 11 weeks of daily telephone calls to the patient to assess pain, sleep, step count, and pain-coping skill practice; if patients were engaged in a progressive walking program; and if they continue to receive care from their primary care clinician. All patients in both groups received these calls.

— In-person CBT involved weekly 30 to 40 minute treatment sessions, where the therapist reviewed the IVR reports and provided feedback during the sessions

— IVR-CBT involved receiving therapist reviews of the IVR reports in a 2 to 5 minute personalized feedback session

 

— Results:

— 82% completed at least 3 treatment sessions, though the IVR-CBT group attended 2.3 more sessions than in-person CBT (8.9 versus 6.6)

— NRS score: IVR-CBT decreased 0.77 points, versus a decrease of 0.84 with CBT, signifying noninferiority. Both groups had statistically significant reductions in average pain intensity at 3 and 6 months post-baseline but not after 9 months. These improvements were considered clinically meaningful changes, though of modest effect size.

— Statistically significant improvements in physical functioning, sleep quality, and physical activity of life at 3 months occurred in both treatment groups, with no difference between the groups.

— Post-treatment, 33% of those with standard CBT reported clinically meaningful improvement in pain intensity of at least 30% compared with 19% in those receiving IVR-CBT, not statistically significant.

— Adverse events: 46 participants, mostly related to increased pain from exercise, no difference between groups

 

— Commentary:

— IVR-CBT seems to offer a more accessible and lower cost treatment option for patients with chronic low back pain, which may well apply to other types of chronic pain (there are data supporting CBT benefit for back pain, osteoarthritis, and fibromyalgia). CBT involves helping patients reconceptualize pain as influenced not only by biological but by psychological, behavioral, and social factors. Patients learn cognitive (e.g. reframing catastrophic thoughts) and behavioral (e.g. relaxation techniques) coping skills through this process, as elaborated in the article.

— It is notable that patients were more engaged with the IVR-CBT-based therapy, attending significantly more sessions, than with standard CBT therapy. This suggests not just the acceptability of this IVR-CBT therapy, but likely also the decrease in burden/increase in accessibility and appeal of this treatment.

— There are several limitations to the study, including the fact that it was carried out in only one VA Hospital and with a small number of patients. Also, there was no nonintervention/placebo arm. However, this last concern may be less significant given that the average duration of pain was 11 years, suggesting that patients actually act as their own control.

— Also, it would be really interesting to know how those with a history of substance use disorder (26% in this article) or those on prescription opioids (12%) would do with IVR-CBT. The numbers of patients in this study was probably too small to get meaningful insight into this.

 

So, this may well be a viable and accessible alternative or adjunct for chronic pain management, and may really help patients who are functionally impaired by the pain, adding to the increasing numbers of nonpharmacologic therapies for this common and difficult problem. It also adds to the impetus for us to offer these types of therapies instead of just jumping to prescribe medications.

see http://blogs.bmj.com/ebm/2016/06/29/primary-care-corner-with-geoffrey-modest-md-tai-chi-for-knee-oa-mindfulness-for-chronic-pain/​ which reviews a few articles: the main one on tai chi for knee arthritis, another on mindfulness-based stress reduction for chronic pain, and another on CBT for back pain

 

 

 

Primary Care Corner with Geoffrey Modest MD: opiates and benzos assoc with inc mortality

28 Mar, 17 | by EBM

By Dr. Geoffrey Modest

Another observational study, this one using data-mining of large patient databases, found that concurrent use of prescription opiates and benzodiazepines was associated with increased ER visits and hospital admissions for opiate overdoses (see doi.org/10.1136/bmj.j760).

Details:

  • 315,428 privately insured patients aged 18-64, continuously enrolled in a health plan with medical and drug benefits from 2001 till 2013
  • About 40% men, comorbid conditions included: heart failure, peripheral vascular disease, hypertension, COPD, diabetes, CKD, cerebrovascular disease, dementia, MI, liver disease, alcohol “abuse” (??not clear how defined), drug “abuse” (also not defined), psychosis, and depression
  • The principle search was for patients on opiates who had at least one day of overlapping prescriptions for a benzo

Results:

  • 9% of opiate users also had a benzo in 2001, increasing to 17% in 2013
  • The increase was largest in those on intermittent opiates
  • Compared to those who did not use benzos, risk of ER visit or hospital admission for opioid overdose was:
    • 14x as often for all opiate users, adjusted OR 2.14 (2.05-2.24, p<0.001)
      • 42x as often for intermittent opiate users, adjusted OR 1.42 (1.33-1.51, p<0.001)
      • ​1.81x as often for chronic opiate users, adjusted OR 1.81 (1.67-1.96, p<0.001)
    • Assuming a causal link between the combo of meds and ER visits/hospitalizations for opioid overdose, eliminating this combo (i.e. not taking benzos) would decrease these services by 15%

Commentary:

  • This is yet another study linking opiates and benzos to overdoses. Other studies done in several different countries have confirmed this, overall finding that around 30% of fatal “opioid” overdoses involve the concommitant use of benzos.
  • There are clear limitations in this study, most of them articulated by the researchers, including that as a retrospective study there could be hidden biases (they controlled only for the ones they assessed), the study only looked at patients continuously enrolled in their health plans (though sensitivity analyses found not much difference if looking at those enrolled for at least 2 years), they did not include patients who died from an overdose, they do not have information on the doses of meds or how those changed over the time period, and they only looked at prescription drugs (i.e. not heroin use or prescription meds bought on the street). They also did a sensitivity analysis requiring both medications overlap for at least 25% of the days of opiate prescriptions, also finding similar results.
  • I would add to this list: it is important to note that the likelihood of hidden biases is increased given that the patients on concurrent opioids and benzos had a higher incidence of every medical condition (14 of them) they tried to control for. Perhaps very significantly in this sicker population, they did not have information on potential differences in the severity of any of these medical conditions in those on benzos vs not (not all diabetes is the same…). And there are some very important conditions that they did not include: for example, they did not look at patients with anxiety disorders, including panic, for which these patients might well be on benzos appropriately for therapy, and these underlying psych conditions themselves have considerable mortality associated with them. Or, bipolar disorders with predominant mania, perhaps misdiagnosed as anxiety and also treated with benzos, yet bipolar disorder itself also has significant attendant mortality. And I should note that of these 14 conditions, the one with the most profound difference between the non-benzo and benzo groups was “depression”, noted in 4.4% in the nonbenzo group and 17% in the benzo group. And, as mentioned, there is no differentiating by severity of depression or comorbid other psych issues (i.e. those on benzos may well have had more psych issues, both quantitatively and qualitatively, which put them at higher risk of overdosing).
  • But, the bottom line to me is that there is certainly a plausible mechanism for increased overdose in those on both meds (benzos increase the respiratory depression of opiates), there is an FDA “black box” caution about simultaneous use of these meds, prior studies have found up to a 10-fold increased mortality from overdose in those on the combo, and so I think the onus is on us as prescribers to minimize the concurrent use of these medications as much as possible. That being said, I certainly do see some patients who are on opiates and do have debilitating anxiety disorders refractory to other meds/therapies, who are also on benzos. Some prescribed by me, some by psychiatrists. I do try to minimize the doses of all of their opiates/benzo. And perhaps it makes sense to try to switch the opiates in those on both classes of medications to buprenorphine, since this is associated with less respiratory depression (though as far as I know this approach has not been validated through studies. I would welcome any information from blog readers). And, it makes sense to be especially certain that these patients have naloxone at home, with someone trained in its administration.

Primary Care Corner with Geoffrey Modest MD: Internet-based improvement in knee pain

6 Mar, 17 | by EBM

By Dr. Geoffrey Modest

There have been several articles recently dealing with nonpharmacologic management of chronic pain (see blogs at end). A recent Australian one looked at the effectiveness of an Internet-delivered training intervention, finding remarkable and apparently durable benefit in patients with chronic knee pain (see doi:10.7326/M16-1714).

Details:

  • 148 people over 50 years old with chronic knee pain: mean age 61, 56% female, 57% urban/43% rural, mean BMI 31, symptom duration 2-10 years in 50%/> 10 years in 27%, 57% employed/30% retired, 38% on acetaminophen combinations/23% NSAIDs/21% on topical anti-inflammatories/only one person on opiates, 50% anticipated moderate improvement by the intervention/17% anticipated large improvement, 60% used the Internet for social media daily
  • Those randomized to the intervention received 3 Internet delivered treatments
    • Educational material about exercise and physical activity, pain management, emotions, healthy eating, complementary therapies, and medications. Those in the control group also received this material
    • An interactive automated physiotherapist-prescribed home exercise in pain-coping skills training (PCST) called PainCOACH, and were asked to complete eight 35- to 45-minute modules, one per week, and practice pain-coping skills daily
    • Seven Skype sessions with a physiotherapist over 12 weeks, sessions lasted 30- 45 minutes(videoconferencing). The physiotherapist performed a brief assessment and prescribed a lower limb strengthening home exercise program to be performed 3 times a week. Exercise progression was monitored. Patients were provided with instructions, video demonstrations, and equipment such as resistive bands and ankle weights.
    • Pain was assessed using an 11 point numerical rating scale (NRS) as well as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 3 months. Primary outcomes were pain during walking using the NRS, and physical function using WOMAC.  Secondary outcomes were knee pain, quality of life, global change, arthritis self-efficacy/coping/pain catastrophizing.
    • The minimum clinically important difference (MCID) for the NRS pain score is 1.8 units, and for the WOMAC physical function subscale is 6 units.

Results:

  • The educational material was accessed by 78% of participants in the intervention group and 88% in the control group. Those in the intervention group attended a mean of 6.3 of 7 Skype physiotherapy sessions and completed 6.4 of 8 of the PainCOACH modules. 68% of the prescribed home exercise sessions and 64% of the PCST practice sessions were completed.
  • The intervention group had significantly more improvement in pain (mean difference 1.6 units) and physical function (mean difference 9.3 units) versus the control group at 3 months.
  • These improvements were sustained at 9 months, with a mean difference of 1.1 units for pain and 7.0 units for physical function.
  • In terms of secondary outcomes: there was significant difference between the groups in essentially all of the secondary outcomes
  • Adverse events from the intervention were minor, with increased knee pain being most common in both groups but more so in the active intervention group.

Commentary:

  • Given the problem with chronic pain meds, be they NSAIDs and their multitude of renal/ GI/cardiovascular complications, or the very significant concerns regarding using opiates for chronic pain, it is reassuring that non-pharmacologic and patient-empowering strategies can be effective.
  • And, as we all know, chronic knee pain is remarkably common: the anticipated projection is that 1/2 of US adults will develop knee osteoarthritis by age 85, but 50% of people with symptomatic knee OA are less than 65 yo.
  • It is notable that the functional differences in the intervention group were well more than what is considered minimally clinically important improvement, and this was almost reached for pain. It is also notable that these benefits were apparent at 9 months, 6 months after the intervention was over.
  • The study had the benefit of having both urban and rural patients, which is especially important for the latter group given their decreased access to face-to-face interventions.
  • One limitation of the study is that it seemed that this was a reasonably healthy cohort, given that most anticipated significant improvement by the intervention and most were only on mild analgesics [They did not define what “acetaminophen combinations” were, in either the article or supplement, but I assume these did not include opiate combinations, since they say only one person was on opiates], and participants could not have such severe knee pain that it limited their ability to exercise.
  • But, as an encouraging result, we in primary care do see lots of patients who have only mild-to-moderate pain, that meds work variably well (and have their toxicities), and it does seem that the results of this 3-month non-pharmacologic intervention is durable for at least the next 6 months.
  • And, it turns out that there currently are a slew of apps available: including Pain Coach (free, but not the same as above), some for back pain exercises, chronic pain relief, several for yoga/meditation, etc. I looked at a couple and they have some useful information, and may be a useful tool to help/empower some patients, though I did not find any as complete as in this study. Let me know if you have found any great ones.
  • So, this study reinforces and adds to the growing body of literature that suggest that a cornerstone of chronic pain therapy, this time for the knee, is non-pharmacologic (see other recent blogs below). One hopeful sign in the US is that in 2016, 87% of those older than 50 and 64% older than 65 do use the internet. I.e., if there are education-level appropriate, linguistically-diverse, culturally-sensitive materials available, they might really help people. Even those who are unable to read could benefit from these materials (perhaps with the help of a younger family member….)

For related articles, see:

http://blogs.bmj.com/ebm/2016/06/29/primary-care-corner-with-geoffrey-modest-md-tai-chi-for-knee-oa-mindfulness-for-chronic-pain/ for a review of an article showing the benefits of tai chi,

http://blogs.bmj.com/ebm/2016/04/07/primary-care-corner-with-geoffrey-modest-md-low-back-pain-improves-with-stress-reduction-mindfulness-and-cognitive-behavioral-therapy/ for an article on the benefits of mindfulness stress-reduction and cognitive behavioral therapy

http://blogs.bmj.com/ebm/2016/03/25/primary-care-corner-with-geoffrey-modest-md-new-cdc-guidelines-for-opiate-prescribing/ reports the CDC guidelines, stressing the use of adjuvant meds prior to starting opiates, though giving short shrift to non-pharmacologic therapies and, for a slew of other articles in the folder: http://blogs.bmj.com/ebm/category/pain/​ ​list

Primary Care Corner with Geoffrey Modest MD: Acute low back pain diazepam not help

1 Mar, 17 | by EBM

By Dr. Geoffrey Modest

An urban emergency room study found lack of utility of diazepam in patients with acute low back pain (see doi.org/10.1016/j.annemergmed.2016.10.002).

Details:

  • 114 patients with acute, nontraumatic, nonradicular low back pain (LBP) of <2 weeks and Roland-Morris Disability Questionnaire (RMDQ) >5 points (a 24-item patient self-administered questionnaire score which measures functional disability, with questions like “I stay at home most of the time because of the pain in my back”, where a 5 point change is considered clinically significant).
  • Mean age 36, 55% male, 73% worked >30hrs/week; median RMDQ score in the ER was 18 [which means substantial functional disability], median duration of LBP before coming to ER 2.5 days, 45% no prior history of LBP/ 48% “few times before”, 5% depressed
  • Randomized to naproxen 500mg bid prn, with either diazepam 5mg or placebo, to take 1-2 tabs every 12 hours prn. All patients got a 10-minute LBP educational session

Results:

  • 112 patients (98%) provided 1-week follow-up
  • At 1 week:
    • Frequency of med use:
      • Naproxen: 70% more than 1x/d, 17% 1x/d
      • Diazepam: 38% more than 1x/d, 32% 1x/d
      • Placebo: 38% more than 1x/d, 29% 1x/d
    • 18 of 57 patients on diazepam (32%) reported moderate or severe LBP
    • 12 of 55 on placebo (22%) had moderate or severe LBP
  • At 3 months:
    • 6 of 50 patients on diazepam (12%) reported moderate or severe LBP
    • 5 of 53 on placebo (9%) had moderate or severe LBP
  • Adverse events: 12 of 57 on diazepam (21%) vs 8 of 55 on placebo (15%)

Commentary:

  • LBP leads to 2.4% of all ER visits (2.7 million annually)
  • Of those presenting with acute LBP, most recover, though 20% have moderate to severe LBP-related functional impairment at 3 months
  • Benzos are sometimes prescribed for sleep and well as for “muscle relaxation”, though the data to support benefit are meager at best. And diazepam is prescribed in about 300,000 ER visits for LBP annually. Hence this study – which showed no benefit but more adverse effects with diazepam
  • The authors comment that most medications do not improve low back pain (see relevant blogs below), also including steroids or acetaminophen; that complimentary therapies (acupuncture, yoga, massage) have little data to support (see blog below on the AHRQ review), and that spinal manipulation is unlikely to benefit ER patients with acute low back pain.
  • This is the same ER group that did a similar study a couple of years ago looking at the efficacy of adding cyclobenzaprine or oxycodone/acetaminophen to naproxen for the same issue (see Friedman BW JAMA 2015; 314(15): 1572), briefly:
    • 323 patients with nontraumatic, nonradicular LBP for < 2 weeks’ duration, given naproxen 500mg bid plus either placebo, cyclobenzaprine 5mg or oxycodone 5mg/acetaminophen 325, to take 1-2 tablets of these q8h as needed, along with a 10 minute LBP educational session
    • They assessed pain by the Roland-Morris Disability Questionnaire (RMDQ), as above
    • Results: at 1-week follow-up, no significant difference between groups, as follows:
      • Naproxen: 72% of patients took naprox >1x/d, 13% took it 1x/d
      • Naproxen, along with:
        • Placebo: RMDQ improved 9.8 points (33% took placebo > 1/d, 31% 1/d)
        • Cyclopbenzaprine: RMDQ improved 10.1 points (31% took it > 1/d, 38% 1/d), more adverse effects than placebo by 13%, NNH (number needed to harm) =7.8
        • Oxycodone/acetaminophen: RMDQ improved 11.1 points (32% took it > 1/d, 21% 1/d), more adverse effects than placebo by 19%, NNH =5.3
      • Overall about 2/3 of patients reported clinically significant improvement 1 week later, though 40% reported moderate or severe pain
      • Also no difference at 3 months, though about ¼ of the patients still reported moderate or severe LBP
    • So, similar to the diazepam study: no evident benefit from either cyclobenzaprine nor oxycodone (though notable perhaps that relatively few patients took the meds much)
    • It should be noted in the oxycodone study that, of multiple exploratory analyses, one did show modest pain relief in the group who took oxycodone more than 1x/d, though the NNT was 6 and the NNH was 5.  So they could not exclude the possibility of modest benefit in those taking more oxycodone
    • See http://blogs.bmj.com/ebm/2015/11/06/primary-care-corner-with-geoffrey-modest-md-opiates-for-acute-low-back-pain/ for a more complete analysis of this study
    • And other studies have not found benefit of the combo of NSAIDs with cyclobenzaprine (either one seems to be equally effective, the combo doesn’t add much)

 

So, these studies do add to the approach to acute low back pain: adding “muscle relaxants” to NSAIDs does not add any clear benefit but does add harms (though another study did find benefit of cyclobenzaprine by itself). And acute treatment by oxycodone, at least in the doses they prescribed, also showed no clear benefit. I would add to this the results from a few other blogs:

Primary Care Corner with Geoffrey Modest MD: opiate prescribing in the elderly and subsequent dependence

22 Feb, 17 | by EBM

By Dr. Geoffrey Modest

Two important articles were just published in NEJM which I think should stimulate a change in clinical practice regarding prescribed opiates.

————————————————————————————

One article assessed the relative importance of physician prescribed opiates and the subsequent use of opioids in the elderly (see Barnett ML. N Engl J Med 2017; 376: 663).

Details:

  • Retrospective analysis of a random 20% sample of continuously-enrolled Medicare beneficiaries who had an emergency department (ED) visit from 2008-2011, and had not received opioid prescription for the prior six months
  • Mean age 69, 65% female, 76% white, 50% also on Medicaid, 37% disabled, mean of 3.5 chronic conditions (most commonly hypertension in 78%, hyperlipidemia in 70%, acute MI in 50%, depression 40%, diabetes 38%, COPD 28%), with 38% from the South/24% Midwest/20% Northeast/17% West
  • ED physicians at the hospitals were classified as either high-intensity or low-intensity opioid prescribers, according to their quartile of prescribing rates at that same hospital.
  • The rates of continued opioid use were compared, defined as 180 days supplied in the 12 months after that ED visit

Results:

  • 215,678 patients received treatment from low-intensity and 161,951 from high-intensity prescribers. The overall clinical characteristics of the patients treated by these different providers were very similar.
  • Within individual hospitals, the opioid prescribing rates varied by the type of providers: 7.3% versus 24.1% (p<0.001), for the low versus high-intensity prescribers. There was minimal correlation between the physicians’ prescribing rate and the median initial dose of the opioid prescribed.
  • There was a 30% increase in long-term use of opioids by patients treated by the high-intensity prescribers, adjusted odds ratio 1.30 (1.23-1.37), p<0.001. The number-needed-to-harm was 49 patients receiving an opioid prescription leading to one excess long-term opioid user.
  • There was a stepwise increase in long-term opioid use, tracking with increased quartiles of physician prescribing rates.
  • Those patients seeing a high-intensity opioid prescriber had higher rates of subsequent hospital encounters (a 3% significant increase) and encounters for fall or fracture (a 7% significant increase), with no difference in non-opioid-related encounters

Commentary:

  • It is notable that the rates of hospitalizations for opioid overdoses in the elderly Medicare population has quadrupled from 1993 to 2012.
  • It is also quite concerning that the elderly are more likely to have adverse consequences from even therapeutic doses of opioids, including more sedation, falls, fractures, and death from any cause.
  • Although this was an observational study, which limited the rigor of its conclusions or its ability to determine causality, these researchers seem to have done an excellent job of including huge numbers of patients, comparing providers in the same institution with each other, and controlling well for likely comorbidities of the patients (though they don’t have a clear assessment of the intensity of the pain of the individual patients, it does seem unlikely that patients would be assigned to high-intensity opioid prescribers just because they had more pain and thereby creating a bias in the study)
  • As noted in several prior blogs, one of my major concerns about opioid prescribing is the dearth of good clinical evidence. This leads to a not so infrequent clinical conundrum: what to do with an elderly patient who has significant chronic pain, perhaps from osteoarthritis, to the point that they have very limited function and extremely poor quality of life. Perhaps a trial of NSAIDs does not help (and NSAIDs have their own attendant morbidities), and neither does acetaminophen nor topical or other adjuvant therapies. Perhaps they have had multiple steroid injections with diminishing or limited effectiveness. And perhaps they are not interested in surgery, or are not healthy enough for it. As a result, to improve their quality of life and after extensive discussion of adverse effects, I have sometimes prescribed tramadol or codeine or even low-dose oxycodone, often in combination with other adjuvant therapies, with excellent clinical and quality-of-life results. And, I think that is in the patients’ best interests and is appropriate care. Even in patients who are 90+ years old.
  • However, this article does reinforce the peril of prescribing opiates to the elderly. Given that the patients given opiates did not seem to differ clinically from those not given opiates, it pretty clearly suggests that we as providers may be playing a significant role in creating long-term opiate users. Our experience in Boston has shown pretty dramatic changes in ED opiate prescribing over the past couple of years. During that time period of this study, it was unusual for one of my patients who had gone to the ED for pain not to come home with an opiate prescription, even if they explicitly stated to the ED doctor that they did not want or need these meds. That is no longer the case. And we should all take seriously studies which show, for example, that even renal colic, considered one of the more severe pains, seems to respond to NSAIDs similarly to opiates (e.g., see Teichman JMH. New Engl J Med. 2004; 350: 684). And many patients do well with NSAIDs post-op (my clinical observation).
  • Although the study targeted older patients, it is consistent with a prior blog in which adolescents with low risk of illicit drug dependence but given legitimate prescription opiates as 12th graders (for surgery, etc.), were up to 3-fold more likely to have opiate use disorder at age 23 (see http://blogs.bmj.com/ebm/2015/11/10/primary-care-corner-with-geoffrey-modest-md-prescribed-opioids-and-future-prescription-opioid-misuse-in-teens/​ )

Given that clinicians seem to be more consciously decreasing/limiting their opiate prescriptions and more hesitant to start opiates, there not only may be fewer prescription opiates available on the street, but also fewer patients requesting/needing continued opiate prescriptions subsequently. So, the more optimistic take on this issue of opiate dependence is perhaps that the future is bright/there may be fewer people with opioid dependence going forward.

———————————————————————————————————————-

An editorial highlighted the huge public health threat of fentanyl (see Frank RG. N Engl J Med 2017; 376:605), making several important points:

  • Fentanyl-related deaths have been increasing dramatically, especially in the eastern United States: from 2628 in 2012, to 5544 in 2014, with 41% of heroin-related deaths involving fentanyl
  • Fentanyl is mixed with a multitude of street drugs, including heroin, MDMA (methylenedioxymethamphetamine), OxyContin, Xanax, and Narco (acetaminophen-hydrocodone). A recent Canadian analysis found that 89% of seized counterfeit OxyContin tablets contained fentanyl
  • Fentanyl is cheap, going for $3500 per kilogram, as compared to $65,000 per kilogram for heroin (and this is despite heroin’s declining prices, which had made it much more attractive in the streets than prescribed opiates, such as Percocet)
  • This all further supports harm reduction strategies, especially since most who die from fentanyl overdose are unaware they are taking it, including: improved monitoring of street drugs for fentanyl, drug enforcement approaches which emphasize use reduction (e.g., not targeting buyers with syringes, which may actually increase the risk of needle sharing and other higher-risk behaviors, etc.), improved access to treatment programs, improved access to naloxone (which, as per prior blogs, may need a higher dose for fentanyl overdoses).

Commentary:

  • This article highlights the devastating and escalating effects of illicit fentanyl, apparently largely produced in China, emphasizing appropriately the importance of harm reduction as a key strategy
  • Of note, I had been unaware that fentanyl was mixed with so many different street drugs, and not just with heroin. This article highlighted how widespread fentanyl-lacing can be, and this message needs to be transmitted to our drug-using population.​

For relevant recent blogs:

http://blogs.bmj.com/ebm/2017/02/10/primary-care-corner-with-geoffrey-modest-md-increasing-deaths-from-opioids/ highlights the increasing opiate death rates, esp from fentanyl

http://blogs.bmj.com/ebm/2016/06/29/primary-care-corner-with-geoffrey-modest-md-tai-chi-for-knee-oa-mindfulness-for-chronic-pain/ describes a study looking at Tai Chi and mindfulness to treat chronic pain

http://blogs.bmj.com/ebm/2016/04/05/primary-care-corner-with-geoffrey-modest-md-meds-for-oa-including-placebo/ is an interesting study finding that even placebo works pretty well for chronic pain from osteoarthritis and, in general http://blogs.bmj.com/ebm/category/pain/​ for a slew of articles on chronic pain and opiates, with descriptions and critiques of published guidelines

 

Primary Care Corner with Geoffrey Modest MD: Increasing Deaths From Opioids

10 Feb, 17 | by EBM

By Dr. Geoffrey Modest

The CDC just published their report tracking drug and opioid-involved overdose deaths in the United States from 2010 to 2015 (see https://www.cdc.gov/mmwr/volumes/65/wr/mm655051e1.htm?s_cid=mm655051e1_x​ ).

Details:

  • Background: from 1999 to 2014 there was a tripling of drug overdose deaths, with 47,055 total drug deaths in 2014, and 60.9% involved an opioid. During 2013-2014, deaths from natural/semisynthetic prescribed opioids [this class includes natural opioids (morphine and codeine), and semisynthetic opioids (oxycodone, hydrocodone, hydromorphone, and oxymorphone)] increased slightly, but there was a rapid increase in deaths from heroin and “synthetic opioids other than methadone” (including tramadol, fentanyl).
  • In 2015, there were 52,404 drug overdose deaths including 33,091 (63.1%) involving an opioid. This death rate calculates to 16.3/100000 population (it was 12.3/100000 population in 2010, a 33% increase)
  • From 2014 to 2015 the death rate from “synthetic opioids other than methadone”, which includes fentanyl, increased by 72.2%, and heroin death rates increased by 20.6%. Natural/semisynthetic opioid death rates increased by 2.6%, but methadone death rates decreased by 9.1%
  • The rates of death involving heroin and “synthetic opioids other than methadone” increased among all demographic groups, regions, and most states (Florida and South Carolina had both decreasing and then increasing trends during this time: Florida decreased from 2010 to 2013 and then increased til 2015; South Carolina decreased from 2010 to 2012 and then increased til 2015)
  • The largest absolute rate increases in deaths from “synthetic opioids other than methadone” occurred in Massachusetts, New Hampshire, Ohio, Rhode Island, and West Virginia. The largest percent increases in rates occurred in New York (135.7%), Connecticut (125.9%) and Illinois (120%). The largest absolute rate increases in heroin deaths were in Connecticut, Massachusetts, Ohio, and West Virginia, and the largest percentage increases were in South Carolina (57.1%), North Carolina 46.4%, and Tennessee (43.5 percent)

Commentary:

  • The above includes 28 states with high quality reporting on death certificates, including specific drugs involved in overdoses. [Seems like all states should be tracking this. And this is why our national statistics and epidemiologic studies pale in comparison to western European countries, where they have large and inclusive national registries. Would be great to fix this…. much better data to act on]
  • Deaths from illicitly-manufactured fentanyl were probably largely responsible for the increase in deaths attributed to “synthetic opioids other than methadone” and were largely concentrated in eight of the 27 states examined. Actual fentanyl prescribing rates did not change during this time [confirming that this was likely illicitly-manufactured]
  • Factors likely involved in these changes include:
    • My guess is that the decrease in overdoses due to methadone is related to more vigorous efforts by the federal and state governments to limit its use in chronic pain. This shows that targeted strategies seem to work.
    • The smaller increase in natural/semisynthetic opioid deaths may also be related to changes in policies/education, use of the prescription drug monitoring program, and legislative changes in naloxone prescription and distribution.
    • The implementation of harm reduction strategies, including syringe exchange programs, increased access to naloxone, more available medication assisted treatments, strategies to reduce the transmission for hepatitis C and HIV, etc., are likely very important in decreasing the extremely important sequelae of drug use
    • But, ironically, it seems that as there is less availability of prescription opioids in opioid prescribing, many patients are taking some more dangerous but now much cheaper drugs such as heroin, which may well be laced with fentanyl (i.e., these opioid substitutes may be being used more, and these may even be more fatal, such as by the increase in fentanyl-related deaths).
  • So, the bottom line here for me is that single targeted measures (decreasing methadone prescribing) can lead to shifts in drug usage with potentially even worse clinical outcomes. Which really speaks to the need to deal with the underlying problems of poverty, lack of hope/avenues to advancement felt by many young (and old) people, lack of positive social supports, poor quality education for many, increasing income inequalities, etc. etc. etc.
  • As I have mentioned in several blogs, including one which evaluated/critiqued the CDC guideline for prescribing opioids for chronic pain (see past blogs below), the issue of chronic pain control is often one of the most difficult clinical issues we encounter in primary care. There are very clear examples (at least to me) of patients who need chronic opioids to function and lead reasonably normal lives. And several need very high doses (for a multitude of reasons, likely including genetic differences in mu receptors). There also are pretty clear examples of clinicians overprescribing opioids, from surgeons/emergency rooms as well as from primary care, and these can have profound social sequelae, such as drug diversion and opioid-related deaths. And, there are whole group of people in the middle, where it is not entirely clear and is a judgment call by the treating clinicians. The first two groups are easier to deal with; this middle group where there is more uncertainty about the need for opiates is quite challenging clinically and more socially concerning given the reality of the explosion of illicit drug use and deaths.
  • I would also like to mention again a prior blog finding that 12th graders prescribed opioids by clinicians (e.g. for surgery) but were considered beforehand to have a very low likelihood of using illicit drugs in the future per a standardized and validated questionnaire, had a much higher rate of opioid abuse at age 23 than a similar group who were not prescribed these opioids (see below).

Past blogs:

http://blogs.bmj.com/ebm/category/pain/ for the array of blogs on opiates and chronic pain

http://blogs.bmj.com/ebm/2016/03/25/primary-care-corner-with-geoffrey-modest-md-new-cdc-guidelines-for-opiate-prescribing/ for a critique of the CDC guidelines

http://blogs.bmj.com/ebm/2015/11/10/primary-care-corner-with-geoffrey-modest-md-prescribed-opioids-and-future-prescription-opioid-misuse-in-teens/ for the blog on 12th graders at low risk of addiction by a validated questionnaire, then getting prescribed opiates, finding that by age 23, there was a 33% increased risk of opioid misuse

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