Low rates of dependence/addiction from opioids for pain relief

I edited the title because it’s been pointed out that “dependence” isn’t the right word. I knew this but was paraphrasing the article title, which uses that word instead of addiction, even though they are clearly talking about opioid misuse. We can thank the DSM-5 for this confusion.

Development of dependence following treatment with opioid analgesics for pain relief: a systematic view – June 2012

Aims: To assess the incidence or prevalence of opioid dependence syndrome in adults (with and without previous history of substance abuse) following treatment with opioid analgesics for pain relief.

Spoiler alert from the happy conclusion:

The available evidence suggests that opioid analgesics for chronic pain conditions are not associated with a major risk for developing dependence.   

Methods

Medline, Embase, CINHAL and the Cochrane Library were searched up to January 2011. Systematic reviews and primary studies were included if they reported data about incidence or prevalence of opioid dependence syndrome (as defined by DSM-IV or ICD-10) in patients receiving strong opioids (or opioid-type analgesics) for treatment of acute or chronic pain due to any physical condition.

Results

Data were extracted from 17 studies involving a total of 88 235 participants.The studies included three systematic reviews, one randomized controlled trial, eight cross-sectional studies and four uncontrolled case series.

Most studies included adult patients with chronic non-malignant pain; two also included patients with cancer pain; only one included patients with a previous history of dependence. Incidence ranged from 0 to 24% (median 0.5%); prevalence ranged from 0 to 31% (median 4.5%).

Conclusions

The available evidence suggests that opioid analgesics for chronic pain conditions are not associated with a major risk for developing dependence.

INTRODUCTION

Many patients world-wide do not receive adequate pain relief because of excessive regulatory restrictions on the availability and accessibility of opioid analgesics.

The problem of opioid over-regulation has been highlighted in reports from

  1. the International Narcotics Control Board (INCB) [1–4],
  2. the World Health Organization (WHO) [5],
  3. the WHO Collaborating Centre Pain and Policy Study Group [6,7],
  4. the Council of Europe [8] and by
  5. non-governmental organizations such as the Open Society Institute and Human Rights Watch

With so many sources showing the opioid restrictions to be problematic, it’s amazing that this side of the opioid-issue is completely ignored.

One reason for undertreatment is the reluctance of physicians to prescribe opioids at adequate dosages, due to concerns linked to possible opioid-induced hyperalgesia and the potential adverse effects, including fatal opioid overdose, development of tolerance and dependence syndrome, harmful use of opioid and diversion.

The fear that patients will develop dependence syndrome is particularly acute when prescribing opioids to treat a chronic non-cancer condition, as both the course of treatment and the patient’s life expectancy of patients are often expected to be long.

A recent systematic review on the prevalence of undertreatment in cancer pain included 26 studies published from 1994 to 2007, and found that approximately 50% of patients are undertreated.

The primary objectives of the present review are to assess the incidence or prevalence of dependence syndrome in adults with and without previous history of substance abuse following treatment with opioid analgesics for pain relief.

Secondary objectives are to assess any differences in the prevalence and severity of dependence syndrome with different types of opioid analgesics, different routes of administration and durations of treatment.

This review was commissioned by the WHO, within the development of the WHO guidelines for pain treatment in adults.

Results

The study by Fleming et al. [45] included 904 patients with chronic non-cancer pain who received daily or intermittent therapy in the previous 6 months; the type of opioid was not reported. Ninety-nine patients (11%) developed dependence.

The study by QuangCantagrel et al. [44] included 86 patients with chronic non-cancer pain treated with time-release morphine, time-release oxycodone, methadone or transdermal fentanyl patch for a mean time of 8.8 months. Only one patient (1%) developed dependence.

The study by Morrison [46] included 198 children and adolescents with sickle cell disease who received meperidine, morphine, hydromorphone or nalbuphine intravenously for 3 days to treat acute pain; treatment was re-started if acute pain recurred. Only one patient (0.5%) developed dependence.

Adams et al. [34] studied 4000 patients with non-cancer pain treated with hydrocodone for 12 months, and reported a 4.9% incidence of dependence.

In the three case series and one RCT described in the systematic review by Littlejohn et al. [32], the reported incidences of dependence were 12.6, 6.9, 24 and 0%, respectively.

Cancer pain

No conclusions can be drawn about the incidence of dependence in cases of cancer pain treatment, because only two studies [40,47] with a total of 118 participants reported data on dependence for these patients

Among the 26 case series included in the Cochrane systematic review by Noble et al. [28], 18 studies did not report whether addiction was observed. Among the studies where dependence was reported, the total incidence was 0.27%.

study by Passik et al. [47] included 100 patients with cancer pain and did not report the type of opioid used or the length of treatment; none of the patients developed dependence (0%).

It was not possible to assess incidence of dependence for subgroups of patients by conditions, because the vast majority of studies did not specify the conditions for which opioids were prescribed.

This is a big part of the problem when merely studying opioid doses in isolation. These studies routinely neglect the conditions for which opioids were prescribed, implying that this would be insignificant (for the researcher, not the patient).

The patient is completely ignored and only medical charts are scanned.

Acute pain

Two studies [39,46] assessed the incidence or prevalence of dependence following opioid given for acute pain in patients with sickle cell disease

In one case series [46], 198 children with sickle cell disease received meperidine, morphine, hydromorphone or nalbuphine with intravenous administration for 3 days, which was re-started if acute pain recurred. Only 0.5% developed dependence.

Method of administration

The majority of studies did not specify the method of administration; thus, it was not possible to assess whether the administration method influenced incidence or prevalence of dependence.

One [41] included 19 patients receiving only intrathecal morphine, and the prevalence of dependence was of 0%;

the other study [46] included 198 patients receiving intravenous administration of meperidine, morphine, hydromorphone or nalbuphine, and the incidence of dependence was 0.5%.

Types of opioid

One study [34] included 4000 patients receiving hydrocodone for non-cancer pain and reported a 4.9% prevalence of dependence.

One study [41] included 19 patients receiving intrathecal morphine for non-cancer pain and reported a 0% prevalence of dependence.

A study [44] including 86 patients receiving time-release morphine, time-release oxycodone, methadone or transdermal fentanyl patch for non-cancer pain reported a 1.1% incidence of dependence.

the data on incidence/ prevalence of dependence in this review can be applied only to patients with chronic non-cancer pain who have used opioids for more than 3 months

Another study [46] included patients receiving meperidine, morphine, hydromorphone or nalbuphine, and the incidence of dependence was 0.5%.

Such patients are probably the most frequently studied with respect to the problem of developing dependence, because they have a long life expectancy and are expected to receive drugs for a long time.

This seems to be what bothers people: why should we take opioids when our condition won’t “improve”?

The public cannot grasp the idea of “pain forever” and the resulting situation of “opioids forever”. People understand that blood-pressure medication and cholesterol-lowering medications must be taken forever, but this understanding doesn’t expand to include chronic pain, which is just as much a “forever” condition as so many others.

After hearing constant PROPaganda about the “dangers of opioids”, the public doesn’t feel it’s safe to treat “just a symptom” of what’s going to be a lifelong pain syndrome.

These studies suffer from low-quality reporting, with little information on the characteristics of patients, type of opioids administered and route of administration.

DISCUSSION

Among almost 2000 titles and abstracts scrutinized, very few assessed and reported data on the development of dependence.

Applying the GRADE methodology showed that the quality of evidence was very low.

The results of the 17 included studies were extremely heterogeneous, with data on dependence indicating incidences ranging from 0 to 24% (median 0.5%), and prevalences from 0 to 31% (median 4.5%).

The observed heterogeneity is due probably to many factors, including

  • the use of different methods to assess dependence,
  • study design, characteristics of included patients,
  • differences in risk factors for the development of dependence and
  • lengths of treatment and follow-up.

The magnitude by which these factors differ could explain differences in incidences or prevalences, but this could not be explored further because the retrieved studies did not report enough information.

The data were inadequate to determine the risk related to specific drugs or method of administration, and it was not possible to retrieve information about the time following prescription of opioids after which dependence occurred, because none of the included studies reported this information

Furthermore, it was not possible to determine directly the specific risk of dependence among patients with history of previous drug abuse, as only one study reported separate data for this subgroup [47].

The most impressive finding of the present review is the deficiency of good-quality studies.

This seems to stand in contrast to the widespread concern of doctors and authorities relating to the prescription of opioids for pain management.

Prospective observational studies of good methodological quality should be designed and conducted to assess incidence of dependence among chronic pain patients.

Such studies should report detailed information on

  • patients’ characteristics,
  • diseases for which opioid is prescribed,
  • type of opioid prescribed,
  • method of administration,
  • doses and lengths of treatment and
  • the lengths of treatment after which dependence occurs.

Moreover, there is a problem in the heterogeneity of the dependence criteria.

Tolerance and withdrawal syndrome plus craving are sufficient for a dependence diagnosis in ICD-10, without requiring loss of control over use and without negative health or social consequences. This is not equivalent to a combination of loss of control and continued use despite knowledge of negative consequences, as is stated in the DSM-IV criteria. Studies should therefore report clearly which criteria are used to assess dependence.

This horrible nightmare was foisted upon us by the DSM-5. Only in the fine print later can you find the qualifications for addiction mentioned: loss of control with compulsive use despite negative consequences.

due to the necessity to treat world-wide diseases involving chronic and non-chronic pain, clinicians should consider the use of opioids because of their proven effectiveness in treating pain and ameliorating quality of life of suffering patients—regardless of the fact that the published literature does not permit a conclusive statement about the risk of dependence.

Hear, hear!

Acknowledgements
This paper has been funded by the WHO Department of Essential Medicines and Pharmaceutical Policies, contract E 19-APW -246.

11 thoughts on “Low rates of dependence/addiction from opioids for pain relief

  1. peter jasz

    ” Low rates of dependence from opioids for pain relief ”

    I believe that should read: ” Low addiction rate (as in 0.6%) for those using opiates for pain relief”
    (Dependence I suspect would be rather high)

    pj

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    Reply
    1. Zyp Czyk Post author

      You’re correct – I just paraphrased the actual article title. I can’t believe that all the smart and very educated psychiatrists would not have realized what a horrible problem it would cause when they call serious addiction just dependence.

      I’m constantly shocked how unintelligent our “thought leaders” are in everything except their own personal narrow specialty. They have no clue how their little ideas will play out in the great big world we all have to live in.

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  2. Lawrence F

    I’ve used narcotic pain relief for near 25 years, most on an oxycontin/Percocet combination, and the last 9 on tapentadol. I will argue to my dying breath the efficacy of these drugs for my neuropathic pain and, in the case of the tapentadol, my ability to maintain a certain level of pain relief & function at a steady dose without the addition of anything for breakthrough pain. And while I believe statistics show the vast majority of legitimate patients with legitimate prescriptions who eventually become addicted either have prior substance abuse/mental health issues or else purposely take the medication other than as directed for their own reasons (keeping a newfound euphoria or to help perform some activity that they should be resting from), I in no way believe that any of us are immune from ‘dependence’ on our pain prescriptions, and that we wouldn’t suffer several DAYS worth of PHYSICAL withdrawal symptoms (as opposed to what, for some ADDICTS, is a LIFETIME of PSYCHOLOGICAL cravings) added to the now unmasked underlying pain of our varied diseases & syndromes.

    Even those physicians who battle to present our side in the opiod debate (Dan Laird, Lynn Webster, Michael Schatman, Jeffrey Singer, Thomas Kline, etc.) go to great length in their papers, articles & tweets to differentiate between tolerance, dependence, & addiction. I think for any of us to do otherwise is to do a disservice to our own cause, in some ways making us seem as unreasoning on our side as Kolodny on his.

    Liked by 1 person

    Reply
    1. Zyp Czyk Post author

      Yes, it’s these oh-aren’t-we-so-clever psychiatrists who came up with the brilliant idea of calling addiction “dependence” so as not to offend anyone who is addicted.

      But they have no problem stigmatizing all pain patients on opioids as “dependent” when it’s no longer separated from “addicted”, even though these are two completely different physical and psychological processes.

      Liked by 1 person

      Reply
      1. canarensis

        LOL!
        “flaming fanny” was purely a rhetorical device for pleasing alliteration, not to be taken literally :-D
        (tho it’s surely true that these people & the whole situation do massively burn my butt…. metaphorically speaking ;-).

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        Reply
  3. canarensis

    (*sigh, tho a happy one*) Another one to print out & take to the doc! :-)

    One of the many things I like about this is, it provides evidentiary backing for my anecdotal claim (which is always dismissed by docs who don’t want to think) that one reason I wanted to remain on the pain med I’d been on for years was…when I get such violent vomiting during migraines that I can’t swallow anything, including water or pain meds for 1-5 days at a time, I don’t go into withdrawal. I’ve tried other meds, & others were AWFUL; I was in blinding agony, vomiting so violently I’d get black eyes, AND got to have withdrawal symptoms on top. Fun time. But most docs refuse to believe it’s even possible to be on an opioid for any length of time without having major dependence…even the ones who accept that there’s a big difference between that & addiction.

    “4000 patients receiving hydrocodone for non-cancer pain and reported a 4.9% prevalence of dependence.” Cripes, that’s way lower than most claims of actual addiction from Rx opioids…”Crisis/epidemic” my flaming fanny.

    Liked by 1 person

    Reply
    1. Zyp Czyk Post author

      I’m intrigued by your “flaming fanny” :-)

      Though I don’t get migraines, my headaches get bad enough to cause vomiting too, so I know how that goes: pain pill, vomit it up, pain pill, vomit it up, and by about the third time, enough of the pain pill has semi-digested to make it effective and then my vomiting stops.

      I think that “real” pain patients value the effectiveness of their medication so highly that we don’t dare abuse them, knowing that if we bump up our tolerance life will only get more painful as opioids become less effective. And it’s not like we’ll ever get an increase in our prescriptions, so we’ll have to make do.

      Liked by 1 person

      Reply
      1. canarensis

        Much sympathy that you know about headaches so bad you vomit violently. When they get to that level, the official diagnosis is purely academic. A more relevant dx would simply be “pure Hell.”

        Liked by 1 person

        Reply
    1. Zyp Czyk Post author

      I always link to the article referenced in my blog posts, but this was a PDF file that was converted into a different format by “Diigo”, the application I use to annotate articles, so the link points to the annotated copy of the PDF file:
      https://www.diigo.com/user/zypczyk/b/498173940

      I can’t find a free copy of the article online anymore, but you can see its sources clearly in this PDF of it in the Journal of Addiction. In the future, I’ll try to make sure to capture the original link before it disappears.

      Liked by 1 person

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