Thursday, March 22, 2012

SAMHSA TIP on Pain & Addiction: Reader Beware

Caveat Lector The U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) recently released a new Treatment Improvement Protocol (TIP 54) on the management of chronic pain in persons with active substance-use disorders or in recovery from such conditions. While this document is recommended reading for all healthcare providers who treat persons with pain, readers also are cautioned that the document has numerous flaws, including biases and misrepresentations of research evidence.

This free, 129-page document, released in 2012 with the title, Managing Chronic Pain in Adults With or in Recovery From Substance Use Disorders: TIP 54, is available for immediate download [PDF here] or in hardcopy format via mail [order online here]. Treatment Improvement Protocols are developed by the Center for Substance Abuse Treatment (CSAT), which is a part of SAMHSA within the U.S. Department of Health and Human Services (HHS).

TIPs reportedly draw on the experience and knowledge of clinical, research, and administrative experts in the subjects under discussion and the documents are widely distributed, sometimes becoming de facto standards of care in the U.S. and other countries. The preface states that, “A major goal of each TIP is to convey ‘front-line’ information quickly but responsibly. If research supports a particular approach, citations are provided”; however, no guarantees are made that there is an established evidence base for all recommended practices — which can be of concern, as described below.

TIP 54 This new document, TIP 54, in intended to equip clinicians with practical guidance and tools for treating chronic noncancer pain (CNCP) in adults with histories of or active engagement in substance-use disorders, namely addiction. The writers note, “By providing a shared basic understanding of and a common language for these two chronic conditions, this TIP facilitates cooperation and communication between health care professionals treating pain and those treating addiction. [It] discusses chronic pain management, including treatment with opioids, and offers information about substance abuse assessments and referrals.

In our own experience with the TIP development process,* SAMHSA/CSAT contracts with an outside medical communications agency to do the heavy lifting of research and writing. Therefore, the quality of any TIP is highly dependent on the writers, who may be skilled at their craft but not at all expert in the subject matter. *This author participated during 2004-2005 on the Editorial Advisory Board for TIP 43, “Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs.”

For TIP 54, the document also was reviewed by a consensus panel of 8 professionals experienced in pain and addiction, and secondarily by a panel of 18 field reviewers. Reviewers are not current government employees, but the TIP does not otherwise describe any conflicts of interest that reviewers may have. These professionals generally help to keep the writers on track, but this guidance may not be rigorously followed in all instances. Also, behind-the-scenes oversight by SAMHSA, CSAT, and other government agency personnel is commonplace and usually plays a role in setting an agenda and tone for the particular TIP.

Challenging & Difficult Subjects

CNCP afflicts roughly 100 million adult Americans, according to the latest revised estimate from the Institute of Medicine [see UPDATE here], and, by some accounts, up to 23 million persons are addicted to drugs and alcohol. Both pain and addiction are multidimensional disorders, with pain afflicting as many as 80% of persons being treated for addiction [Leavitt 2006, ref below]. The two disorders generally share common neurobiological pathways, but each presents unique complexities and challenges when it comes to diagnosis, treatment, and prognosis. Treatment may involve numerous approaches administered by practitioners from diverse medical disciplines.

As the TIP writers note, “Chronic pain and addiction are not static conditions. Both fluctuate in intensity over time and under different circumstances and require ongoing management. Treatment for one condition can support or conflict with the other; a medication that may be appropriately prescribed for a particular chronic pain condition may be inappropriate given the patient’s substance use history.” Of course, a particularly difficult problem is treating pain in these patients with potentially addicting psychotropic substances, including opioids, sedatives, and other agents.

Therefore, combining discussions of pain and addiction in one document was no doubt a difficult undertaking. To briefly summarize the TIP, the writers state…

“This TIP advises clinicians to conduct a careful assessment; develop a treatment plan that addresses pain, functional impairment, and psychological symptoms; and closely monitor patients for relapse. Even the best treatment is unlikely to completely eliminate chronic pain, and efforts to achieve total pain relief can be self-defeating. Patients may benefit when clinicians team with other professionals ( e.g., psychologists, addiction counselors, pharmacists, holistic care providers). Patients must also assume a significant amount of responsibility for optimal management of their pain. Educating patients, family members, and caregivers in this process, and helping patients improve their quality of life, can be gratifying for everyone involved.”

Certainly, this seems like a reasonable and sound approach to the subject. Where this TIP goes astray is in its biased perspectives and in some of the details, or, in many cases, lack of attention to detail. All of the key points covered in TIP 54 have been studied in multiple research investigations, some more adequately than others. Unfortunately, citing but one or, at most, a couple of references for important data or observations, as is done in this document, suggests that the writers did not consider all relevant research. In some instances, the presented data may be inaccurate by not taking into account the diversity of research available.

In that regard, it is disappointing that government documents almost always seem to rely on older research and data, which may be outdated or superseded, and TIP 54 is no exception. Although this document was just released in 2012, almost all of the cited references are from 2007 or much earlier, with only a smattering of more recent citations. One would think that the researchers/writers would have consulted more current studies, especially for topics like pain and addiction for which there is a rapidly expanding body of scientific literature.

The writers do state in the preface that “most of the research that forms the evidence base for a particular TIP is not provided in the TIP itself,” which is a curious limiting of information in a putatively scholarly publication. They further note that all supporting research can be reviewed via the Internet at the Knowledge Application Program website [here]; however, as of March 21, 2012, there was no literature review listed for TIP 54 at that site.

Biased Perspectives & Inaccurate Reporting

Critics of medical research and reporting have proposed that many wrong, or at least unreliable and invalid, therapeutic answers are being generated due to bias of some sort [discussed in UPDATE here]. Broadly speaking, bias is anything that potentially distorts the assessment and presentation of evidence and influences invalid conclusions. Bias almost always either exaggerates, undervalues, or otherwise misrepresents evidence to favor the arguments or perspectives of the writer; it can be evident in what is said as much as in what is selectively omitted from a discussion. A brief examination of TIP 54 reveals several typical examples of bias and/or the misinterpretation of evidence (in order of where they appear in the document):

  • At the outset (p. 1, Exhibit 1-1), and perhaps setting the tone of this TIP, the writers note that 32% of patients with chronic pain may have an addictive disorder, which is an alarmingly large number that could amount to more than 30 million Americans with concurrent chronic pain and addiction. However, the sole reference for this is a study by Chelminski et al. [2005, see full citation below] that examined patients with high levels of psychiatric comorbidity being treated for chronic pain in a primary care setting. Of only 85 patients enrolled, hence constituting a very small trial, 27 were found to have a substance misuse disorder. However, when recruiting patients, the investigators specifically sought subjects who were having difficulty managing pain and/or suspected of misusing opioid analgesics. Therefore, this was a highly select group of patients and the only surprise was that merely 32% exhibited substance-use disorders. However, this hardly supports the TIP writers’ implication that nearly a third of typical patients with chronic pain have or develop comorbid addiction.

  • A 3-paragraph discussion of cannabinoids (marijuana) suggests that synthetic congeners of this agent show promise for treating pain, but concludes that, “The consensus panel does not recommend smoked marijuana for treating CNCP” (p. 37). No evidence is cited or discussed to indicate how this conclusion was reached, but this stance might be expected of a federally-funded document. It completely ignores the fact that, as of last year, 13 states and the District of Columbia had enacted laws permitting the use of medical marijuana by qualified patients [see UPDATE here]. Furthermore, a number of physicians’ groups have emphasized the need for placing patients above politics by examining marijuana’s scientific validity as an effective medication [see UPDATE here]. Some day, risks outweighing benefits of smoked marijuana might be demonstrated by high-quality evidence; until then, there seems little justification for the consensus panel’s biased and unqualified conclusion.

  • Nonpharmacologic approaches could be important in patients with pain and addiction, but the TIP writers discuss complementary and alternative medicine (CAM) in a mere two paragraphs (p. 38). CAM therapies might include chiropractic, massage, acupuncture, nutritional therapies, and many others. The writers dismiss these with a statement that the supporting evidence is “ambiguous” and that, “Many systematic reviews of CAM research note generally poor-quality reporting and heterogenous methodology that precludes definitive evidence-based conclusions.” For this sweeping assertion they cite one reference and, while much of the research on CAM has indeed been of poor quality and contentious, it would seem deserving of more thorough investigation and discussion than evidenced in this document — unless there was a bias against CAM.

  • In their introduction to a discussion of opioid therapy for pain, the TIP authors state, “Opioids are potent analgesics that may provide relief for many types of CNCP. However, even when effective, they have limitations, such as diminished efficacy over time” (p. 40). While it is true that opioids have many limitations, the lack of long-term efficacy is a myth without supporting evidence at this time [see discussion of this and other opioid myths in an UPDATE here].

    One of two references used by the TIP writers to substantiate their broad statement is a reasonably good-quality systematic review and meta-analysis of evidence by Noble et al. [2008, ref below]. These researchers actually found very large effect size SMDs (Standardized Mean Differences) of 1.99 for oral opioids and 1.33 for intrathecal opioids favoring pain relief for at least 6 months. Followup times ranged from 6 to 48 months and, while not all patients benefitted long-term, the researchers conclude there appears to be no indication in the clinical-trial evidence to suggest that efficacy automatically diminishes with time.

    The second reference is to an essay by Ballantyne [2006, ref below] discussing long-term opioid therapy for CNCP. She concedes that a preponderance of low-quality evidence (eg, case studies) suggests that patients can attain satisfactory analgesia, using moderate non-escalating opioid doses, for at least 6 years. Yet, Ballantyne has continued in more recent years to bewail the lack of an extensive evidence base in support of long-term opioid therapy. This perspective may have merit, but it is only one side of an unbalanced dialog regarding opioid analgesics — apparently accepted by the government as expressed in this TIP — and there also are arguments on the other side that favor long-term opioid therapy for patients who benefit until there is reliable and valid evidence to contraindicate it.

  • A small but important point: The writers suggest that an option for patients with active addiction and CNCP is treatment with buprenorphine, as a transition from opioid into non-opioid or nonpharmacologic forms of pain management (p. 43). They do not mention any research to support the validity of this approach and they state, “buprenorphine prescribed specifically for pain is currently an off-label use.” Apparently, neither the writers nor reviewers were aware that a buprenorphine patch (Butrans®) was FDA-approved for pain in July 2010 — which, as in many other areas of the document, questions the thoroughness of their background research.

  • The TIP writers discuss difficulties of opioid analgesic therapy regarding the development of tolerance and opioid-induced hyperalgesia (OIH, p. 45). They concede that, “In a clinical setting it may be impossible to distinguish between the two conditions, and they may coexist.” However, as we discussed in a prior UPDATE [here], evidence to support the importance or even the existence of OIH in human subjects being treated with long-term opioids clinically for pain is weak and highly contestable, at best. Yet, OIH is presented in this TIP as if it is a well-established and accepted phenomenon that commonly hinders opioid therapy.

  • TIP 54 supports the use of urine drug testing (UDT) as an important tool for improving patient care (p. 51), yet there is no discussion of good-quality clinical evidence to verify that assumption. To support the importance of UDT, the writers cite a study by Couto et al. in 2009 that reported of more than 900,000 patients tested 75% showed at least one sign of nonadherence to their prescribed opioid regiments. We had previously described this study in an UPDATE [here], pointing out how this data-mining research was biased and flawed in so many ways that any conclusions drawn from it could not be accepted as valid. One must question whether the TIP writers read beyond the study abstract.

  • In a section on drug diversion (p. 60), the TIP writers seek to assure readers that fears of a Drug Enforcement Agency (DEA) “crackdown” on clinicians prescribing opioids for pain is based on false beliefs. As evidence, they reference an old, online DEA policy statement from 2006 [available here]. However, this may reflect more what the DEA, and SAMHSA in this TIP, would like readers to believe than the actual truth; a well-documented report from the CATO Institute at about that same time, titled “Treating Doctors as Drug Dealers, The DEA’s War on Prescription Painkillers” [available here] tells of a much different and harsher reality.

  • Finally, and inexplicably, there is no mention anywhere in TIP 54 of naloxone — a simple, effective, FDA-approved antidote for opioid overdose. Also puzzling is that overdose itself, as a serious risk of opioid therapy used for pain or addiction, is mentioned but three times in the document, even though opioid-related overdose deaths have been touted as an “epidemic” by various U.S. government agencies. Whether this was a careless omission or part of some hidden agenda is unknown; either way, it seems inexcusable.

The above points are only a handful that piqued our interest during a first read of TIP 54, much more could be said. Individually those criticisms might seem of limited consequence; taken together, they appear to depict an agenda driven by strong biases that eschew more evidence-based and fair-balanced perspectives.

So, Why Read This TIP?

Despite the concerns and criticisms noted above, there are at least 3 reasons why healthcare professionals, and inquisitive patients, should at least briefly examine TIP 54:

  1. This document is not entirely without merit, especially for newcomers to either the pain or addiction fields, and some of the assessment tools, approaches to treatment planning, and listings of other resources might be of special interest. A great deal of taxpayer funds, as well as time and effort by many well-meaning professionals, went into developing the TIP; so, it should not be ignored merely because it has what we consider to be flaws — provided those defects are recognized and taken into account by readers.

  2. SAMHSA/CSAT-developed Treatment Improvement Protocols are often used as models of acceptable and/or expected patient care by other U.S. agencies at the federal and state levels, as well as by government and non-governmental agencies outside the U.S. TIPs are readily available and distributed widely, with a potential for significant impact on public policy and health.

  3. Perhaps most importantly, government-sponsored documents of this nature are often referenced and quoted in other reports and articles. Unfortunately, some writers may use TIP 54 as an appeal to authority for bolstering their own biased arguments, depending on how they selectively choose data and conclusions from the TIP. By reviewing this document, readers may better understand when and how attempts are being made to influence them via the skillful use of such rhetoric.

Therefore, TIP 54 is worthy of at least a quick glance, but as we often have advised in the past, caveat lector — reader beware. And, as always, readers are invited to comment below, whether they agree or disagree with our viewpoints.

> Ballantyne JC. Opioids for chronic noncancer pain. Southern Med J. 2006;99(11):1245-1255 [
abstract here].
> Chelminski PR, Ives TJ, Felix KM, et al. A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity. BMC Health Svs Res. 2005;5(3) [
article here].
> Leavitt SB. Pain in Opioid-Addicted Patients Entering Addiction Treatment. 2006 (revised; adapted from Addiction Treatment Forum, 2004 (Winter);13(1) [
PDF available here].
> Noble M, Tregear SJ, Treadwell JR, Schoelles K. Long-term opioid therapy for chronic noncancer pain: a systematic review and meta-analysis of efficacy and safety. J Pain Sympt Manage. 2008;35(2):214-228 [
abstract here].

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