Origins of the 21st Century Opioid Epidemic

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Aether2000

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The 21st century opioid epidemic began through a series of events that resulted in significant relaxation of criteria for opioid prescribing and a willingness to prescribe much higher doses than had been seen previously. It was due to drug company pseudoscience, legislatures and medical boards who rolled back restrictions on prescribing and developed new legislation to promote medical prescribing, quasi-governmental agencies such as JCAHO adoption of the "5th Vital Sign", pain society promotion of opioids, inadequate basis for "board certification" of physicians prescribing pain medications, naivite of doctors that in some cases turned to insouciance as they prescribed ever escalating dosages for increasingly flimsy reasons, doctors turned drug dealer as a criminal enterprise, and patients who clamored for greater access to opioids through patient advocacy groups. The culmination of years of escalating dosages and deaths produced a bubble of millions of patients that are chemically dependent, some of which much later turned to heroin. Below is a timeline I created to demonstrate the origins of the current epidemic.


• 1950 Percodan FDA approved

• 1952 Purdue Frederick, a small struggling pharmaceutical company founded by doctors John Purdue Gray and George Frederick Bingham in 1892 operating in New York City, was purchased by three psychiatrist brothers Raymond Sackler (1920-2017), Arthur Sackler (1913-1987), and Mortimer Sackler (1916-2010) of New York City. Purdue Pharma L.P. was formed in 1991 as one of the branches of the company and is the namesake it is known by in sales and business. Purdue Frederick Laboratories (Totowa New Jersey). Purdue began developing pain management medications. By 2015 the Sackler family became the 16th most wealthy family in the country with assets of $14 billion dollars, nearly all due to Oxycontin. Purdue has had sales totaling $35 billion since 1995 when Oxycontin was approved. (Forbes, July 1, 2015)

• 1954 Levorphanol tartrate (Levo-Dromoran) introduced

• 1960 Fentanyl synthesized by Paul Janssen. It was approved for IV use as a combination drug with droperidol in 1968, a combination that was believed to limit abuse potential of the IV drug due to the significantly bad psychiatric effects of the droperidol at high dosage. The combination drug, Innovar, was produced after pure fentanyl ran into roadblocks in the FDA approval process and was staunchly opposed by the venerable field leader Robert Dripps, MD. Once a compromise was reached between Dripps and Janssen with fentanyl being formulated in combination with droperidol, it was used in neuroleptanalgesia. In 1972, IV fentanyl was approved by the FDA as a single drug in 1ml vials, 50mcg/ml. (J Pain 2014;15(12):1215-26)

• 1970 British Medicine Journal article stating “Intractable pain of non-malignant origin is nearly always best treated other than by narcotic analgesics since their continued use must lead to dependence.” “Tolerance develops relatively quickly- sometimes a dosage of 500mg of morphine a day is reached within 10 days”. (Br Med J. 1970 May 30;2(5708):525-6

• 1973 International Association for the Study of Pain (IASP) formed

• 1974 Percocet FDA approved (Schedule II drug)

• 1977 American Pain Society (APS) formed as a component society of the IASP

• 1977 The prevailing attitude was that opioids for chronic non-malignant pain should be avoided. (Analgesic drugs in the management of pain. Halpern L. Arch Surg 1977 Jul;112(7):861-9) “The use of potent narcotics to control severe pain should be of short duration and limited to patients with acute diseases or inoperable or metastatic cancer who require long-term relief. Continued and prolonged use of narcotics in patients with chronic benign pain is not recommended because of serious behavioral consequences, the development of tolerance, and addiction liability. Long-term use of analgesic drugs in chronic pain usually produces negative behavioral complications that are more difficult to manage than the pain it was desired to eliminate.”

• 1978 Vicodin 5/500 approved by FDA (Knoll Pharmaceutical) as a Schedule III drug, permitting up to 5 refills, could be called in to a pharmacy without a written prescription, and with recommended maximum dosing 8 tabs per day due to the acetaminophen (40mg hydrocodone).

• 1978 Colpaert FC published an article “Long-term suppression of pain by narcotic drugs in the absence of tolerance development” (Arch Int Pharmacodyn Ther. 1978Dec;236(2):293-5)

• 1979 A rat study demonstrated chronic pain alone produces hypoalgesia, chronic narcotics alone cause hyperalgesia, tolerance to narcotics in animals with chronic pain may not develop. (Colpaert F, Life Sciences 1979 Mar26;24(13):1201-9)

• 1980 Jane Porter and Hershel Lick wrote a letter to the NEJM entitled “Addiction Rare in Patients Treated with Narcotics”, describing 4 cases of addiction in 11,882 hospitalized patients receiving opioids identified by the Boston Collaborative Drug Surveillance Project. Patients received at least one dose of opioid as part of their medical treatment. They wrote that "the development of addiction is rare in medical patients with no history of addiction." This one paragraph letter was used extensively by opioid manufacturers in the 1990s to demonstrate the very low rate of addiction in opioid users.

• 1980 Forest S. Tennant Jr. MD of the UCLA School of Public Health published medical-legal guidelines for prescribing narcotics to habitual and addicted narcotic users in California and western states. In this paper (West J Med Dec 1980;133(6):539-45) he laid the legal framework within confines of a medical practice of treatment of pain in addicts and described the ability and restrictions on treating addicts. In particular with dual diagnosis he made a legitimate case for prescribing opioids for chronic pain patients.

• 1980 The American Chronic Pain Association was formed as an advocacy and education group for chronic pain patients.

• 1981 Buprenorphine (injectable) “Buprenex” approved by the FDA

• 1982 S Perry and G Heidrich published a study entitled “Management of pain during debridement: a survey of US burn units” (Pain 1982;13:267-280) In this study of 10,000 burn patients, there were no reported cases of addiction. This study was extensively used in advertising by opioid manufacturers to sell their medications.

• 1983 Forest Tennant published an article describing (-)alpha-Acetylmethadol (LAAM) for the treatment of chronic pain in abusers of opioids. In 3 of 4 patients, pain was relieved and opioid abuse was eliminated (Drug Alcohol Depend. Nov 1983;12(3):243-7) He concluded LAAM may be very helpful in the treatment of chronic pain, especially given the 72 hour half life of the drug

• 1983 American Academy of Algology founded taken from the name algos, Greek for pain, and logy- Greek for study. However, “algology” was long in use by the scientific community for the study of algae. In 1985, the American Academy of Algology changed their name to the American Academy of Pain Medicine . This organization was significantly supported by opioid manufacturers later in time according to New York Times, US Government, and this author’s personal attendance at their annual meetings.

• 1984 First annual meeting of the American Academy of Algology

• 1984 Dilaudid and Dilaudid HP FDA approved (Schedule II drug).

• 1984 A study on slow release oral morphine showed no correlation between analgesia and plasma level of morphine. (Vater M, Smith G, Aherme GW Pharmacokinectics and analgesic effect of slow-release oral morphine sulphate in volunteers Br J Anaesth 1984 Aug;56(8):821-7) <This reinforced the concept of titration to analgesia instead of fixed amount dosing for pain, and justified escalating doses.>

• 1984 A letter to the editor entitled “Pain, the physiological antagonist of opioid analgesics” (GW Hanks, RG Twycross Lancet June 30 1984;1(8392):1477-8) contended that pain itself reduced the effects of analgesics, implying a measure of safety if pain were present during their use.

• 1986 Russell Portenoy and Kathleen Foley published a paper on the use of mainly low dose opioids among 38 non-cancer patients with no reported misuse/addiction. This small study was widely quoted by drug manufacturers and champions of opioid prescribing for the next 25 years as evidence of low addiction risk. Specifically, the authors concluded in the prestigious journal Pain, [25(1986):171-86] “For non-cancer pain, narcotics “can be safely and effectively prescribed to selected patients with relatively little risk of producing the maladaptive behaviors which define opioid abuse.” (Gounder, C. New Yorker Magazine, Nov. 8, 2013)

• 1986 World Health Organization develops their analgesic ladder, including opioids, and encouraged the treatment of cancer pain with opioids

• 1986 Nyswander ME and Dole VP Published a paper “On the use of methadone to limit physical dependence in the treatment of chronic pain” (In: Foley KM, Inturrisi CE, editors. Advances in Pain Research and Therapy. Vol. 8. New York: Raven Press; 1986. pp. 187–190). This article may have promoted the prescribing of methadone for chronic pain. Methadone later turned out to have ten times the rate of death compared to other opioids.

• 1987 MS Contin approved by FDA and was marketed exclusively for cancer pain initially according to the 2003 GAO report on Oxycontin

• 1987 Cephalon founded by Frank Baldino (pharmacologist), Michael Lewis (neuroscience), and James C. Kauer (organic chemist), all three former scientists with DuPont. Cephalon developed Actiq, Fentora, Nuvigil, and Provigil. In 2008 Cephalon paid 425 million to the federal government due in part to marketing Actiq for off label uses. Cephalon was acquired by Teva in 2011.

• 1987 Utah board of medicine established guidelines regarding the use of controlled substances to treat pain

• 1988 Study on hydromorphone blood levels and pain control concluded “Knowing that there is a low concentration of narcotic in the blood of a patient with chronic severe pain who is receiving high drug doses and who shows lack of both efficacy and side effects may reassure health care professionals that further narcotic dosage escalation is appropriate.” MM Reidenberg et al Clin Pharmacol Ther 1988 Oct;44(4):376-82)

• 1988 Forest Tennant, D. Robinson, A Sagherian, and R Seecof published a paper (NIDA Res Monogr 1988;81:174-80) that discusses a systematic clinical evaluation of 52 chronic non-malignant pain patients with a mean age of 49 years, evenly divided male/female, that were referred for treatment of severe intractable pain after having failed several other therapies. “Once pain relief was achieved, patients did not escalate their dosage, and they were able to maintain pain relief for long time periods. Opioids used were different for different patients and had a daily dosage range of hydromorphone 8-120mg, methadone 10-240mg, oxycodone 15-80mg, meperidine 200-2000mg, and morphine 60mg. Although opioids produced dependence in all patients and complications of constipation and edema in about one third, high daily opioid dosage treatment appeared to be the only medical means to achieve adequate pain control in these subjects”. The author measured plasma levels of these drugs and found several of those taking codeine and some taking methadone had no detectable levels of these drugs.

• 1988 Minnesota board of medicine established guidelines regarding the use of controlled substances to treat pain and Virginia established intractable pain policies

• 1988 American Academy of Pain Management founded and later began offering “Certificates in Pain Management” to non-physicians after paying a fee then taking a short written test. This organization changed their name to the Academy of Integrative Pain Management in 2016

• 1988 American Medical Association recognizes Pain Medicine as a specialty and that year the American Academy of Pain Medicine seated its first member in the AMA House of Delegates

• 1989 Massachusetts board of medicine issued guidelines regarding use of controlled substances to treat pain, Texas launched an intractable pain treatment policy

• 1989 Weissman & Haddox created the term “pseudoaddiction” based on their experience with a 17 year old leukemia patient with chest wall pain who appeared to be addicted due to inadequate pain medication. (Pain 1989 Mar;36(3):363-6) This term was later used by opioid manufacturers to promote opioid overuse and by addicts to justify higher doses should be prescribed by physicians. Haddox later became Vice President of Health Policy at Purdue, manufacturer of Oxycontin

• 1989 Review article “Opioids in chronic pain” by HJ Mcquay noted “patients who are prescribed opioids for the management of sensitive pain do not become addicts. To deprive them of this means of pain relief is unjust.” HJ McQuay Br J Anesthes.1989 Aug 63 (2):213-219

• 1989- The term “breakthrough pain” first appeared in the medical literature (Cancer 1989;63:2284-2288), coined by Russell K. Portenoy, M.D., Mathelyn Maldonaldo, RN, Ronald Fitzmartin PhD, Robert F. Kaiko PhD, and Ronald Kanner, MD in an article regarding cancer patients receiving MS Contin for pain. Portenoy was the principle author and published at least 26 other articles regarding “breakthrough pain”.

• 1990- The venerable R. Melzack published “The tragedy of needless pain” in the widely read Scientific American magazine [Sci Am. 1990 Feb; 262(2):27-33.] and this article was considered seminal in enhancing prescribing of opioids for chronic non-malignant pain. In this article he stated: “ Many people suffer not because their discomfort is untreatable but because physicians are often reluctant to prescribe morphine…many care givers, afraid of turning patients into addicts, deliver amounts that are too small or spaced too widely to control pain. Yet the fact is that when patients take morphine to combat pain, it is rare to see addiction.”

• 1990 RK Portenoy and NA Hagen characterized “breakthrough pain”, and published an article about its characteristics. (Pain 1990; 41:273-81)

• 1990 Russell Portenoy and Kathleen Foley along with C. Inturrisi published a paper in Pain 1990 Dec;43(3):273-86 stating “opioids should not be withheld on the assumption that pain mechanism, or any other factor, precludes a favorable response. “….the clinical use of opioids should include dose escalation to maximally tolerated levels and repeated monitoring of analgesia and other effects” “In 1990 Russell Portenoy was quoted in other journal articles advocating for the use of opioids for chronic non-malignant pain (J Pain Symptom Manage. 1990 Feb;5(1 Suppl):S46-62.

• 1990 Fibromyalgia was coined and used to justify the treatment of pain without any objective signs or symptoms, without any known cause or pathophysiology

• 1990 Clinical Journal of Pain established as the American Academy of Pain Medicine’s first official journal

• 1990 Arizona state medical board issued guidelines regarding the use of controlled substances to treat pain and California developed an Intractable Pain Therapy Act, Section 2241.5. California’s policy specifically stated “No physician or surgeon shall be subject to disciplinary action by the board for prescribing or administering controlled substances in the course of treatment of a person for intractable pain” with the exception the patient may not being treated for chemical dependency or with medications used for a non-medical purpose.

• 1990 Duragesic approved by FDA (Schedule II drug) and was used primarily for cancer pain initially. The initial studies in fentanyl patch technology was from Alza, a small pharmaceutical company that began working on the technology in 1984 after developing a commercially successful scopolamine patch.

• 1991 S Schug, A Merry, and R Acland published an article in Drugs [1991Aug;42(2):228-39] stating “Inadequately treated acute and chronic pain remains a major cause of suffering, in spite of enormous advances in pharmacology and technology. Opioids provide a powerful, versatile, widely available means of managing this pain, but their use is too often restrained by ignorance and mistaken fears of addiction. However, problems (such as tolerance, physical dependence, addiction and chronic toxicity), anticipated from experience with animal experiments and pain-free abusers, seldom cause difficulties when opioids are used appropriately to treat pain (so-called 'dual pharmacology'). “

• 1991 Postgraduate Medicine article Morphine myths: sedation, tolerance, addiction was published (67 Suppl 2 S100-2) by M. Zenz who argued “Morphine and other strong opioids are still, more than 180 years after the synthesis of morphine, not adequately used in clinical practice and many patients suffer unnecessarily severe pain in consequence. Governments limit morphine usage by legal restrictions. The underuse of morphine and its restriction in many countries is mostly due to prejudice and myths which clinical experience does not show to be true. Morphine is a very safe drug, correctly prescribed in chronic pain therapy, the only severe side effect being constipation.”

• 1991 Brian Goldman, MD published a paper (CMAJ. 1991 Jun 15;144(12):1660-4.) entitled “Analgesics and chronic pain: “If all you have is a hammer, every disease is a nail” exploring opioid use in chronic non-malignant pain. In this paper, Russell Portenoy is quoted saying about “several large prospective studies that were completed in the 1980s with surprising results: “They concluded that the documented incidence of iatrogenic addiction to prescribed narcotic painkillers was of the order of 4 cases per 10,000 patients. These data suggest that patients with no prior history of alcoholism or abuse or street drugs are at extremely small risk of developing these behaviors when given opiate drugs therapeutically for the treatment of pain.”

• 1991 Oregon and Georgia medical boards issued guidelines regarding the use of controlled substances to treat pain

• 1991 Oramorph FDA approved as a Schedule II drug (Roxane Laboratories)

• 1991 American College of Pain Medicine founded (became the American Board of Pain Medicine in 1994)

• 1992 Russell Portenoy published an article “Chronic Opioid Therapy for Non-Malignant Pain: From Models to Practice” (APS Journal later known as Pain Journal 1992;1(4):285-88) In this journal he fully makes the transition from treatment of cancer pain to non-cancer pain with opioids. “The general applicability of a biopsychosocial model of chronic pain might lead to the expectation that some patients with nonmalignant pain respond to opioid therapy in a manner that mirrors the typically favorable response of the cancer pain patient, just as some patients with cancer pain demonstrate psychological disturbances and disabilities reminiscent of a severe chronic nonmalignant pain syndrome. The most reasonable approach is probably one that is commonly accepted for other inadequately studied analgesic treatments, namely, empirical patient selection followed by a therapeutic trial. The concept of the therapeutic trial has not been applied to the use of opioids for chronic nonmalignant pain, despite the lack of any compelling reason to avoid the approach.” Portenoy goes on to critique the guidelines for opioid prescribing for chronic non-malignant pain created by Dr. Chabal and colleagues, who advocated of only one formulation of a single opioid drug, inform their patients ‘the more you take it, the less it works’, and that additional medication requests are automatically refused suggesting the patient has a drug problem. Portenoy argues for “flexibility” in opioid use, that there is “evidence in the clinical literature analgesic efficacy seldom declines over time unless there is worsening in the underlying pathology”, and that requests for higher doses may have multiple causes including pseudoaddiction, tolerance, worsening underlying pain in addition to addiction. He also notes Dr Chabal neither mentioned a therapeutic trial nor a “treatment holiday”, and there was no discussion of the “need for sophistication in opioid pharmacotherapy”.

• 1992 Russell Portenoy and R Payne published a chapter “Acute and chronic pain in “Comprehensive Textbook of Substane Abuse” Baltimore: Williams Wilkins 1992;714 in which 25,000 pain patients treated with opioid narcotics were reviewed and found only 7 demonstrated a “true addictive lifestyle” with the risk of true addiction 0.3% of the population suffering with chronic non-malignant pain.

• 1992 E. Richard Blonsky, MD became president of the American Academy of Pain Medicine

• 1992 Zenz, Strumpf, and Tryba published a paper describing long term treatment of 100 patients with opioids for chronic pain (J Pain Symptom Manage 1992 Feb;7(2):69-77) with morphine (daily dose mean 255mg with a range of 20-2000mg/day) stating 51% received good pain relief, 28% partial pain relief, and 21% did not have good pain relief in a mean 7 month treatment period. Functional improvement was directly correlated to reduction in pain. They also concluded there was no cases of addiction and no side effects other than nausea and constipation, and “Our results indicate that opioids can be effective in chronic nonmalignant pain”

• 1992 Colorado developed an intractable pain treatment policy

• 1992 the Agency for Health Care Policy and Research developed a policy on the assessment of post-operative pain stating “opioid analgesics are the cornerstone of pharmacological postoperative pain management” and “psychological dependence and addiction are extremely unlikely to develop after patients without prior drug abuse histories use opioids for acute pain”. They also stated initial postoperative dosing should be on a scheduled basis rather than prn, then later may use Q4H prn dosing. <the encouragement of post op pain opioid dosing by physicians ultimately led to chronic use and an increase in the rate of addiction>

• 1992 First board certification of physicians practicing pain by the American College of Pain Medicine

• 1992 First board certification of pain physicians by the American Board of Anesthesiology- hundreds of doctors from 1992-1998 without any formal pain training at all were certified by the board as having “Specialized qualifications in pain management” after taking a written test. Hundreds of physicians could now claim “board certification in pain medicine” without training, opening up a pandora’s box of opioid prescribing.

• 1992 American Academy of Pain Medicine incorporated in Illinois

• 1993 Oralet (fentanyl solid sweetened “lollipop” lozenge was released by Abbott Laboratories as a Schedule II drug for preoperative drug sedation in children in the hospital setting and for treatment of painful procedures in adults and children. It was developed beginning in 1985 by Theodore H Stanley with clinical trials beginning in the late 1980s. Janssen declined to bring it to FDA approval so another company was formed, Anesta to develop oral transbuccal fentanyl citrate. During pre-approval clinical trials with Oralet, Drs. Perry Fine and Michael Ashburn contemplated the use of the drug in cancer patients for break through pain, a term championed by Portenoy. Oralet was later withdrawn due to nausea from the drug. The blood levels achieved were much lower than the later released Actiq and Fentora.

• 1993 Alaska, Texas, and Wyoming state boards of medicine issued guidelines regarding the use of controlled substances to treat pain and Washington issued an intractable pain treatment policy

• 1993 First ACGME accredited pain fellowships beginning with approximately 35 programs. These programs from 1993-2000 were taught by mainly by anesthesiology faculty, doctors that primarily were operating room or labor pain doctors at the time. “As a result, many new pain specialists were intellectually or clinically unprepared by their formal training to assimilate the burden of managing chronic pain” (Bonica’s Management of Pain by Scott Fishman published 2012 p. 1560) The first multidisciplinary requirements for fellowship training in pain medicine were not implemented until 2006 implying many doctors trained in fellowship before that point potentially had inadequate training in chronic pain management. Bonica, the father of pain medicine recognized the need for a multidisciplinary approach in 1947

• 1993 Purdue launched Partners Against Pain according to a website, a program designed to connect patients with pain management therapies including opioids. The Partners Against Pain website contained many articles with misinformation, attempting to downplay the addictiveness of opioids and overstating their safety (https://www.fda.gov/ohrms/dockets/dockets/01n0256/c000297-A.pdf)

• 1994 Robert N Jamison PhD, Karen O. Anderson PhD, Christine Peeters-Asdourian MD, and Michael F. Ferrante MD published a paper “Survey of opioid use in chronic nonmalignant pain patients” Regional Anesthesia Jul-Aug 1994;19(4):225-30 Two hundred seventeen patients being treated for pain at two pain centers completed a questionnaire, and one hundred twelve were taking oral opioids for pain. Of those taking opioids, 83% felt that opioids were moderately beneficial in relieving their pain, 25% believed the opioid had not lost its ability to relieve the pain over time, and 35% reported no need to increase their medication. 36% expressed no fear of addiction or dependence, and 56% had no unwanted side effects.

• 1993 American Academy of Pain Medicine inaugurates its Comprehensive Review Course in Pain Medicine

• 1994 the International Association for the Study of Pain defined chronic pain as a clinical entity distinct from acute pain or “pain”.

• 1994 the Agency for Health Care Policy and Research developed a policy on the assessment of cancer pain.

• 1994 California Board of Medicine adopts guidelines for opioid prescribing: Except for gross negligence, “A physician and surgeon may prescribe for, or dispense or administer to, a person under his or her treatment for a medical condition dangerous drugs or prescription controlled substances for the treatment of pain or a condition causing pain, including, but not limited to, intractable pain. (b) No physician and surgeon shall be subject to disciplinary action for prescribing, dispensing, or administering dangerous drugs or prescription controlled substances in accordance with this section." Alabama state medical board issued guidelines regarding the use of controlled substances to treat pain and Florida issued a pain treatment policy for intractable pain.

• 1995 the American Pain Society conducted a quality improvement oriented literature review on the treatment of acute and cancer pain concluding: (a) a report of unrelieved pain raises a “red flag” that attracts clinicians’ attention (b) making information about analgesics convenient where orders are written (c) promising patients responsive analgesic care and urging them to communicate pain (d) implementing policies and safeguards for the use of modern analgesic technologies; and (e) coordinating and assessing implementation of these measures (JAMA 1995 Dec 20;274(23):1874-80)

• 1995 December 12, the FDA approved Oxycontin (Purdue Frederick Pharma) in dosages of 10, 20, and 40mg “for the treatment of moderate to severe pain lasting more than a few days”. The 80 and 160mg tablets were approved later. The highest dosage tablet was equivalent to 24 tablets of 10mg hydrocodone or 48 tablets of 5mg hydrocodone.

• 1995 Idaho state medical board issued guidelines regarding the use of controlled substances to treat pain, and Missouri, Oregon, and Nevada issued an intractable pain treatment policy. (

• 1995 The American Pain Society introduced the concept of pain as a vital sign in a November 1995 presidential address of James Campbell, MD, not as a directive. Dr. Campbell stated “Vital signs are taken seriously. If pain were assessed with the same zeal as other vital signs are, it would have a much better chance of being treated properly. Quality care means that pain is measured and treated.” (Campbell JN. APS 1995 Presidential address. Pain Forum. 1996;5:85–8)

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• 1996 Steven Feinberg became president of the American Academy of Pain Medicine

• 1996 Prescribing guidelines for opioids published (Drugs 1996 May;51(5):713-37) that noted, “there is an increasing acceptance of the role of opioids in the management of recurring acute pain, chronic nonmalignant pain of organic origin and severe neuropathic pain. At all times, uncontrolled pain should be addressed by gradual increase in the opioid dose until either pain control is achieved or intolerable and unmanageable adverse effects supervene.”

• 1996 “Management of chronic non-malignant pain” was published (Br J Clin Pract 1996 Sep;50(6):324-30) with Drs. Steen Andersen and G. Leikersfeldt opining “Chronic non-malignant pain is often treated inadequately because of opiophobia. There is no scientific justification for this fear. With close monitoring and frequent controls, opioids are safe for this kind of pain. There is no scientific evidence that patients with chronic non-malignant pain are more prone to addiction or tolerance.”

• 1996 RL Brown, MF Fleming, and JJ Patterson published a case series report (J Am Board of Fam Pract 1996;9:191-204) of 566 patients suggesting opioid maintenance for low back pain was safe and effective for many.

• 1996 Colorado, Florida, Maryland, Montana, North Carolina, and Washington state medical board issued guidelines regarding the use of controlled substances to treat pain and Wisconsin issued an intractable pain treatment policy.

• 1996 Kadian FDA approved (F. H. Faulding and Company Limited)

• 1996 FDA sent a warning letter to Purdue for advertising MS Contin in promotional materials that contain statements, suggestions, or implications that are false or misleading in violation of the Federal Food, Drug, and Cosmetic Act, in spite of repeated notification to Purdue that claims of product superiority were unsupported and were false or misleading advertisers. (FDA Docket 01n0256/c000297-A)

• 1996 Pain & Policy Studies Group from the University of Wisconsin School of Medicine was formed to do education, research and policy development on the use of opioids for treatment of chronic cancer and non-malignant pain. Their focus is in achieving access to opioids to enhance the quality of life of people living with painful diseases, and addresses regulatory environments governing professional healthcare practice relating to pain management and access to prescription opioids for severe pain relief.

• 1996 Purdue began marketing Oxycontin with a label warning stating Oxycontin tablets were to be “swallowed whole and were not to be broken, chewed, or crushed because this could lead to rapid release and absorption of a potentially toxic dose of oxycodone”, effectively telling drug addicts how to get high using the drug. Purdue began marketing the drug nationwide, initially to pain physicians then to primary care physicians, then to surgeons and other physicians in lavish “doctor speaker training” seminars, it was stated to the participants that there was no upper limit on opioid pain medications, and that addiction was extremely low in those taking opioids. Oxycontin was the only opioid with blood level vs time graphs included in the package insert in which the blood levels were plotted on a logarithm scale- effectively smoothing the curves and making it appear Oxycontin lasted much longer than it did.

• 1996 The American Pain Society trademarked the phase “Pain:The 5th Vital Sign” and began heavily promoting its use and the concept, using a 0-10 scoring system for pain. Ultimately this focus on a single dynamic of pain resulted in doctors prescribing opioids to treat the subjective number the patient generated, and ultimately resulting in increasing pain medication morphine equivalent dosages.

• 1996 American Academy of Pain Medicine publishes Definition of Pain Medicine

• 1997 Contemporary Nurse (Contemp Nurse 1997 Jun:6(2):61-6) published an article “The stigma and enigma of chronic non-malignant back pain (CNMBP) treated with long term opioids (LTO)”. Authors Gardner and Sandhu stated “Many patients with severe CNMBP suffer not because their pain is untreatable but because their pain and personhood have not been validated by doctors and nurses who are opioiphobic. Such ignorances, fears, beliefs, and biases not only deny some CNMBP patients adequate pain relief but also puts their lives at risk as it has long been recognized that chronic pain can lead to immunosuppression, affecting morbidity and mortality. “

• 1997 Norco 10/325 approved by the FDA, effectively increasing the amount of hydrocodone that could be prescribed by 300% on the basis of the acetaminophen compared to Vicodin 5/500, the initially approved form of hydrocodone

• 1997 Endo pharmaceutical was formed acquiring products from DuPont Merck Pharmaceutical Company, who had previously acquired Endo laboratories established in 1920. The founders of the company were Carol Ammon, Mariann MacDonald, and Louis Vollmer in 1997, acquiring the trademarks and patents for Percodan, Percocet, and ER Morphine. Sales increased from 138 million in 1999 to 252 million in 2001, 399 million in 2002, 596 million in 2003, and 615 million by 2004.

• 1997 American Pain Foundation (APF) founded by three past presidents of the American Pain Society as an independent national patient advocacy organization for those living in pain. The organization was heavily supported by the opioid industry pulling in $5 million in support each year by 2010 and also by the American Academy of Pain Medicine, itself supported by opioid manufacturers. The APF had a forum called “Painaid” that was strongly supportive of opioids and the rights to obtain opioids regardless of the severity of side effects or death. The website exaggerated the benefits and downplayed the side effects of opioids, stating the side effects were minor and would go away “after a few days”. They also said on their website that there was “no ceiling dose for opioids as long as they are not combined with other drugs such as acetaminophen, and that the dosage can gradually be increased over time if the pain worsens. The foundation board members had extensive ties to opioid manufacturers. The APF opposed in court a 2001 Ohio class action pain patient lawsuit against Purdue for obscuring risks of Oxycontin. The foundation said Ohio was plagued by “opiophobia”. The APF had a profound effect on patients obtaining opioids in America, and held lawyer authored articles on their website about how patients may exercise legal rights to opioids. The APF closed suddenly in 2012 after a Propublica and US Senate investigation into the foundation as a front for drug manufacturers.

• 1997 American Medical Association developed policies to protect physicians from “excessive regulatory scrutiny, inappropriate disciplinary action, or criminal prosecution” when appropriately prescribing controlled substances to relieve intractable pain. Also the AMA “opposes harassment of physicians by agents of the Drug Enforcement Administration in response to the appropriate prescribing of controlled substances for pain management” Policy H-120.960

• 1997 Consensus Statement on Opioids for Chronic pain was developed as a joint statement by the American Pain Society and the American Academy of Pain Medicine authored by David Joranson, MSSW, founder of the UW Pain and Policies Group. This statement suggested that opioids were safe and effective for chronic, noncancer pain and that the risk of addiction was low. “Misunderstanding of addiction and mislabeling of patients as addicts results in unnecessary withholding of opioid medication”. “Studies indicate that the de novo development of addiction when opioids are used for the relief of pain is low”. Importantly, the statement also included “Furthermore, for most opioids, there does not appear to be an arbitrary upper dosage limit, as was previously thought” and “….It is now accepted by practitioners of the specialty of pain medicine that respiratory depression induced by opioids tends to be a short-lived phenomenon, generally occurs only in the opioid-naïve patient, and is antagonized by pain. Therefore, withholding the appropriate use of opioids from a patient who is experiencing pain on the basis of respiratory concerns is unwarranted.” The coauthor of the paper was David Haddox, DDS, MD (chairman of the committee) who at the time was a paid speaker for Purdue Pharma, and who would become a Purdue Pharma executive three years later. Between 2000 and 2010 Purdue paid the UW Pain Group 1.6 million dollars. (John Fauber, Milwaukee Journal Sentinel April 4, 2011) The UW Pain group received in total 2.5 million dollars from all opioid manufacturers, paid in advance with most of the monies. Other members of the committee developing this statement included David Joranson, Albert Brady, MD, Daniel Carr, MD, Richard Blonsky, MD, Kim Burchiel MD, Melvin Gitlin, MD, Matthew Midcap, MD, Richard Payne, MD, Dana Simon MD, Sridhar Vasudevan MD, Peter Wilson MBBS and the Consultant was listed as Russell K. Portenoy, MD. The statement was approved by the AAPM Board June 29, 1996 and the APS Executive Committee August 20, 1996 and released in 1997.

• 1997 the Federation of State Medical Boards (FSMB), developed the first model guidelines for prescribing opioids. This policy was developed by several people with ties to narcotic manufacturers including Dr. J. David Haddox, MD who became the Purdue VP for Health Policy in 1999. Reportedly the FSMB also accepted money from pharmaceutical firms to produce and distribute narcotics-prescribing guidelines. (Gounder, C. New Yorker, Nov 8, 2013). This influential guideline was subsequently adopted or modified by state medical boards and state legislatures to provide guidance for prescribing. These guidelines, used by individual state medical boards and state legislatures to develop policies, stated “physicians should not fear disciplinary action” from the FSMB, for “prescribing, dispensing, or administering controlled substances, including opioid analgesics, for a legitimate medical purpose and in the usual course of professional practice” The American Academy of Pain Medicine participated in the development of these model guidelines.

• 1997 The State of California passed Senate Bill 402 that provided a “Pain Patient Bill of Rights”. This included provisions that “A patient who suffers from severe chronic intractable pain has the option to choose opiate mediations to relieve severe chronic intractable pain without first having to submit to an invasive medical procedure, which is defined as surgery, destruction of a nerve or other body tissue by manipulation, or the implantation of a drug delivery system or device”. “The patient’s physician may refuse to prescribe opiate medication for the patient who requests a treatment for severe chronic intractable pain. However, that physician shall inform the patient that there are physicians who specialize in the treatment of severe chronic intractable pain with methods that include the use of opiates” “A physician who uses opiate therapy to relieve severe chronic intractable pain may prescribe a dosage deemed medically necessary to relieve severe chronic intractable pain, as long as that prescribing is in conformance with the California Intractable Pain Treatment Act, Section 2241.5 of the Business and Professions Code”. This act added Part 4.5 (commencing with Section 124960) to Division 106 of the Health and Safety Code, relating to health. This Pain Patient Bill of Rights was widely circulated through the pain patient population nationally and was touted on pain forums as their right to receive opioids.

• 1997 Russell Portenoy established the Department of Pain Medicine and Palliative Care at Beth Israel Medical Center and serves as its chairman

• 1998 Rollin M. Gallagher published an editorial in the Clinical Journal of Pain (Clin J Pain Sept 1998;14(3):185-6) entitled “Outcomes and Moral Hazards in the Medical Culture of Opioid Phobia” He would later become a member of the board of directors, then ultimately president of the American Academy of Pain Medicine in 2009

• 1998 Pharmacotherapy (Nov-Dec;18(6):1313-22) published an article entitled “Safety issues in the pharmacologic management of chronic pain in the elderly” by Shimp. In this article it is stated “Despite evidence to the contrary, fear of dependence is the major barrier to their appropriate prescription. Psychologic dependence is rare in patients receiving long-term therapy for pain with opioids”

• 1998 AG Finkel, TC Toomey, S Abashian, and JD Mann published a paper in The Pain Clinic (1998;10:235-43) that described chronic non-malignant pain being treated with a mean daily dose of 23.3 +/- 7.3mg methadone. Forty of the patiens had a mean therapy of 18 months. Side effects were peripheral edema (19%) and nausea (15%). At a two year follow-up interval 14 of the original 59 patients continued using methadone for pain management (19 were lost to follow-up). A later paper continued analysis on these patients (William F. Taylor MD, Alan Finkel MD, Kevin Robertson PhD, Abigail Anderson MD, Timothy Toomey PhD, Sandra Abasian RN, and J Douglas Mann MD Pain Medicine Sept 2000;1(3):254-259) found the mean initial dosages of those that continued methadone treatment was 23mg rising to a mean of 31mg at the end of the two year period. Reasons for discontinuation of methadone in the 40 patients remaining in the study at 2 years: 15% were discharged due to non compliance (including one who was arrested for CII prescription fraud), 20% discontinued due to ineffectiveness, 30% discontinued due to intractable side effects, 10% died, and 7.5% were taken off all opioids due to resolution of their pain condition. Of those that discontinued methadone, 42% continued with other opioids at an average of 77mg morphine equivalent dosage. Of those that remained on methadone, 79% required dose escalation, with the highest dose prescribed 50mg methadone/day. There was one suicide in the study and two attempted suicides.

• 1998 In the journal of Law and Medical Ethics (Winter;26(4):332-49, 263), Allison Martino argued “a complex ‘ethic of under prescribing’ underlies the continued reluctance of physicians to use opioids to treat chronic pain. She contends that state medical boards are uniquely positioned to promote a new ethic for pain management, but stresses the difficulties for boards in attaining this goal, changing their approach to pain management and persuade a skeptical medical community that adopting a risk for under prescribing will serve the long-term interests of patients and the profession”

• 1998 CS Hill presented a lecture at the AAPM annual meeting in 1998 claiming “experience has shown that when very large doses of narcotics were given to patients with bona fide pain, they became more functional and productive, and did not become dysfunctional drug-seekers.” (Pain Physician 2000;3(1):65-68)

• 1998 Actiq (fentanyl) approved by the FDA for treatment of opioid tolerant cancer patients. Actiq had been developed by Anesta Corporation as an off shoot of clinical trials with Oralet as an idea of Perry Fine and Michael Ashburn to use it for breakthrough pain. Unlike Oralet, that was an oral lollipop, Actiq was meant for buccal use after it was discovered analgesia was produced in 10-15 min after application in that manner. Absorption of fentanyl in Oralet is 25-30% but in Actiq is 50%. Anesta Corporation was purchased by the larger company Cephalon in 2000. After this acquisition, Actiq became widely used for chronic non-malignant pain, and in 2008 Cephalon, the manufacturer, paid a $425,000,000 fine to the FDA for allegedly conducting off-label marketing of the drug from 2001-2006 for migraine headaches, radiation therapy, sickle cell crisis, changing dressings, and injuries, and in patients who were not opioid tolerant. (#08-860: Biopharmaceutical Company, Cephalon, to Pay $425 Million & Enter Plea to Resolve Allegations of Off-Label Marketing (2008-09-29))

• 1998 Oxyfast (trademark) first used commercially. Oxyfast was a 20mg/ml liquid solution of oxycodone hydrochloride with a relatively rapid onset, used for “breakthrough pain”. This preparation had the initial trademark filed in 1994, but by 2009 it was discontinued by Purdue Pharma. This preparation was so potent that 1 teaspoon = 150mg morphine equivalent or 15-10mg Vicodin. It quickly became a favorite medication.

• 1998 Roxicodone 15 and 30mg tablets approved by FDA (Roxane)

• 1998 The National Pain Foundation was formed as a patient advocacy group for access to opioids including a physician referral list of opioid prescribers. The foundation ceased operations in 2010, having transferred its assets to the American Pain Foundation, but then was relaunched in 2012 after the American Pain Foundation ceased operations after a Congressional investigation into their funding

• 1998 The American Academy of Pain Management endorsed the AAPM/APS Consensus statement released in 1997.

• 1998 The American Geriatric Society Guidelines for treatment of pain that included the statements: “Pain relief should become a priority”, “Opioid pain relievers are effective in relieving moderate to severe pain”, and “Regulatory agencies should make opioid pain relievers more readily available”.

• 1998 Purdue created a video promotion named “I Got My Life Back” and distributed 15,000 copies to be used in physician waiting rooms as a “check out” item for an office’s patient education library. This video featured a doctor who stated “So, these drugs, which I repeat, are our best, strongest pain medications, should be used much more than they are for patients in pain.” A year later the overall opioid painkiller prescriptions filled jumped by 11 million (CNN report by Sonia Moghe May 12, 2016 entitled Opioid history: From “wonder drug” to abuse epidemic)

• 1998 The Veterans Health Administration premiered a national strategy initiated by the Undersecretary for Health intended to improve pain management for its patients, and adopted “Pain as the 5th Vital Sign”. This resulted in a significant increase in opioid prescribing. Because the VA did not allow their opioid prescriptions to be entered into any state prescription monitoring programs (as late as 2017), there were a significant amount of substance abuse and many opioid overdoses due to patient double dipping.

• 1998 J. David Haddox became the American Academy of Pain Medicine president

• 1998 Federation of State Medical Boards Model Guidelines for the Use of Controlled Substances for the Treatment of Pain (developed in 1997) were published

• 1998 American Academy of Pain Medicine and the American Headache Society jointly form the Pain Care Coalition

• 1998 AMA adds self-designated specialty for Pain Medicine

• 1999 Dr. Seddon R Savage published a paper in the Medical Clinics of North America (1999 May;83(3);761-6) stating “Opioids are a necessary and effective component of the management of chronic non-cancer related pain in some patients” and “the therapeutic use of opioids is uncomplicated in the majority of patients using opioids”

• 1999 Henry McQuay argued in a pain series published in Lancet (1999 Jun 26;353(9171):2229-32) that “Opioids are our most powerful analgesics but politics, prejudice, and our continuing ignorance still impede optimum prescribing” and “patients with chronic pain may suffer longer and unnecessarily if we prescribe and legislate badly”.

• 1999 The use of CR medications to titrate to stable doses and pain control (compared to the traditional IR titration) was shown to be equivalent in a paper published in the Journal of Pain Symptom Management (1999 Oct;18(4):271-9) by Salzman, Roberts, Wild, Fabian, Reder, and Goldenheim. This article opened the door for initial prescribing of continuous release products that was ultimately used in Emergency Departments, post surgery, and as an initial drug for chronic non-malignant pain treatment.

• 1999 Twenty states by this point in time had passed new laws, regulations, or policies moving from near prohibition of opioids to use without dosing guidance. The State of Washington (WAC 246-919-830, 12/1999) passed a law stating “No disciplinary action will be taken against a practitioner based solely on the quantity and/or frequency of opioids prescribed”

• 1999 The VA introduced the 5th Vital Sign as a means of assessment and treatment of all patients in their hospitals and subsequently developed policies that encouraged liberal opioid prescribing.

• 1999 The Oregon State Medical Board disciplined a doctor for not prescribing enough narcotics to reduce pain in 6 patients from 1993 and 1998. The physician was ordered to undergo psychiatric treatment for his treatment of these patients, specifically not prescribing pain medications to a 35 year old patient with wheezing and a 82 year old man with congestive heart failure complaining he could not breath. Dale Austin the deputy executive vice president of the FSMB said at the time, “Such actions might increase” and the New York Times reported on this disciplinary action September 4, 1999, causing concern by physicians across the country they may be disciplined for under-prescribing opioids. The Times also stated, “Advocates of better pain treatment said doctors simply needed to educate themselves about current medical thinking. And several said the Oregon case represented only the beginning of the sea change in how the public believed pain should be treated.

• 1999 American Academy of Pain Medicine, American Society of Addiction Medicine, and the American Pain Society created the Liaison Committee on Pain and Addiction (LCPA)
 
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• 2000 A journal article entitled Bedside perspectives on the use of opioids: transferring results of clinical research into practice by Ravenscroft P and Schneider J (Clin Exp Pharmacol Physiol. 2000 Jul;27(7):529-32) it was stated “Clinical trials of opioids have shown that pain can be controlled in the great majority of patients.” and “The evidence cited suggests that, in the long-term treatment of cancer pain, respiratory depression almost never occurs.” and “Tolerance may occur, but is not a clinical problem and should not impair their use [opioids] in adequate doses to relieve the patient’s pain.”

• 2000 A 12 month study of transdermal fentanyl in doses from 50-100mcg/hr provided pain relief in 65% of those reporting very good, good, or moderate pain relief. However by 12 months, 63% of those enrolled discontinued treatment, with a 28% incidence of nausea, 17% somnolence, 15% constipation, and 15% vomiting. (Pain Med June 2000;1(2):206)

• 2000 Journal article in JAMA (2000 Apr 5;283(13):1710-4) that concluded despite significant increases in opioid prescribing from 1990-96, there was no significant increase in opioid abuse.

• 2000 In a journal article by JM Mossey and RM Gallagher (Pain Med 2000 Dec;1(14):340-50) it was concluded both pain and depression levels were strongly inversely related to physical function, and that treating pain and depression in the elderly may reduce functional impairment.

• 2000 Edward C. Covington MD in an article entitled “Opioiphobia, Opiophilia, Opioagnosia” discussed the pros and cons of opioid prescribing. In this paper (Pain Med Sept 2000;1(3):217-23) he stated “The recent initiatives by JCAHO and the Veterans Administration should help to relegate such attitudes [withholding opioids] to the past. Adopting pain as a 5th vital sign ensures that we will know when our patients suffer unrelieved pain. Our own organization [ABPM] has issued a position paper affirming the appropriateness of chronic opioids as a therapeutic tool in these conditions [chronic non-malignant pain], and most states have adopted legislation or regulations that specifically endorse this form of treatment. We must support such policies and legislative liberalization. A number of articles followed [the 1986 Portenoy and 1990 Melzack papers] supporting opioid maintenance, and enthusiasm for this has grown rapidly. The condemnation of opioids in chronic pain has now been replaced in many places by unbridled enthusiasm. Headlines scream that there’s a cure for pain but doctors are afraid to use it. We lack good data, but we cannot delay treatment until the answers are in. One area of agreement is the lack of systemic toxicity in chronic opioid use. Respiratory depression occurs only when the dose is increased beyond the point of sedation, and tolerance to this effect develops quickly. [Functional] impairments are thought not to be sufficient to preclude safe driving and other activities. Some studies actually found that healthy subjects and those with chronic pain had improved cognition when acutely given morphine. Fears of iatrogenic addiction have been fueled by misunderstanding of pseudoaddiction. It is reassuring to learn that the increased medical use of opioids has not led to an increase in evidence of abuse. Even in the case of those with pre-existing substance abuse or addictive disorder, a small literature shows that opioid treatment can be successful. Specialists in pain medicine are seeing patients whose lives are essentially restored by this [opioid] therapy, leading to great enthusiasm for their use. “ Covington also discusses the potential hazards and caveats in opioid usage.

• 2000 American Board of Physical Medicine and Rehabilitation began administering the ABA pain exam and offering “grandfathered” certifications to hundreds up to a thousand doctors without training in pain medicine by taking a written exam. This continued until 2006 with the American Board of Neurology and Psychiatry being the next board offering “pain certification” for doctors without any training in pain medicine.

• 2000 First media reports of Oxycontin abuse and diversion in rural areas of Appalachia then spread to larger cities. Individuals and communities were devastated by addiction and death related to Oxycontin. In West Virginia, half the patients admitted to a drug treatment center was due to Oxycontin abuse and over 200 deaths in Florida were due to Oxycontin

• 2000 JCAHO, the major credentialing body for American hospitals, introduced standards for pain assessment and management in 2000 (effective 2001), stressing patient rights to pain assessment and treatment, not only in hospitals but across multiple settings, and with both acute and chronic pain included. All patients were to have pain assessed and managed until 2009 then the standard was revised. These pain standards were developed over a two year period in conjunction with the University of Wisconsin, Madison School of Medicine Healthc Benchmarks. 2001 Jun;8(6):68-70, 62. The standards did not require the use of drugs, but it was stated they would give hospitals “requirements for improvement” if they failed to meet this standard. Among these standards: “Patients have the right to appropriate assessment and management of pain (RI.1.2.9). The JCAHO also published a book for physicians as part of required education seminars. The book cited studies that claimed “there is no evidence that addiction is a significant issue when persons are given opioids for pain control” and called doctors’ concerns about addiction side effects “inaccurate and exaggerated.” This book was Purdue sponsored. (CNN report May 12, 2016)

• 2000 VA Pain Toolkit national implementation of pain policy. “Emphasize to the patient that the patient’s self-report of pain is the single most reliable indicator of how much pain the patient is experiencing: and “Ask the patient what pain rating would be acceptable or satisfactory to him/her”.(Section 2). “It is important that all practitioners be aware of how their own biases may influence pain assessment” including “Fear of patient addiction. Concern that attention to pain may encourage additional complaints of pain and medication seeking.” “Barriers within the healthcare system may be due to ….Restrictive regulation of controlled substances” (Section 3) “Q. What is an acceptable pain score? A. Pain level that is not distressing and one that allows you to sleep, eat, and perform your regular daily activities.” (Section 4) https://www.va.gov/PAINMANAGEMENT/docs/Pain_As_the_5th_Vital_Sign_Toolkit.pdf

• 2000 On October 31, 2000, the US Congress passed a bill that designated the period from January 1, 2001 to Dec. 31, 2010 as the “Decade of Pain Control and Research”. With this designation, it was hoped that public and clinical attention and funding for research would be focused on the “serious and under-recognized public health crisis of chronic pain.” The American Academy of Pain Medicine participates in this process.

• 2000 Edward C. Covington, MD became president of the American Academy of Pain Medicine

• 2000 Pain Medicine, the new official journal of AAPM, publishes its first edition

• 2001 The American Board of Family Practice published a review article on chronic pain citing patients unwarranted fear of addiction, physician negative attitude regarding opioids, and physician lack of knowledge about opioids, and fear of regulatory scrutiny as barriers for adequate treatment of pain. (J Am Board Fam Practice 2001 May-June; 14(3):211-218)

• 2001 In a journal article by Bill H McCarberg (family physician) and Robert L Barkin (pharmacist), it was stated the controversy over using opioids to treat chronic pain was due to regulatory barriers, and misunderstanding about pain analgesics used for chronic pain. The authors argued long acting opioids have greater utility than short acting opioids, and that improved quality of life is directly related to the use of long acting opioids in patients with either malignant or benign pain. Furthermore, the authors argued short acting opioids should be avoided in chronic pain.

• 2001 AG Lipman argued regularly scheduled low dose opioids should be an option in the treatment of osteoarthritis pain (Curr Rheumatol Rep. 2001 Dec;3(6):513-9.)

• 2001 The Kentucky Board of Medical Licensure developed guidelines for physicians on prescribing opioids for chronic pain

• 2001 Oxycontin sales exceeded $1 billion dollars a year. Purdue discontinued distribution of their 160mg tablet due to concerns about abuse and diversion. Purdue launches “In the Face of Pain” website that contained a toolkit for media, legislative issues, community groups, and professional organizations. The website was shut down by Purdue in 2015.

• 2001 The Pain Care Coalition established the CMS new code for Pain Management services (code 72). Separately, the American Society of Interventional Pain Physicians worked on obtaining a pain code by CMS.

• 2001 The American Academy of Pain Medicine co-sponsors educational programs, in collaboration with JCAO, focusing on new pain management standards

• 2002 Forest Tennant MD and Laura Herman RN published a paper entitled “Self-Treatment with Oral Transmucosal Fentanyl Citrate to Prevent Emergency Room Visits” (Pain Medicine June 2002;3(2):186-7) 90 chronic pain patients “with a variety of painful conditions” were treated with a long-acting opioid. All additionally used a short-acting oral, suppository, or injectable opioid for self-treatment of emergency flares. All were given oral transmucosal fentanyl citrate (Actiq) to alternatively substitute for their current opioid to self-treat emergency flares. After 3 months or more of use, 96% believed they could safely and effectively treat their emergency pain flares with OTFC. 79% believed the OTFC prevented them from having to visit an emergency room or hospital for pain control. <This off label usage and prescription of OTFC for non-malignant pain encouraged other doctors to do the same, leading to a significant increase in OTFC use in the chronic pain population>

• 2002 Sanford H Roth published an article entitled “A new role for opioids in the treatment of arthritis (Drugs 2002;62(2):255-63) in which it was stated “neurobiological research has confirmed the basis for 24-hour around-the-clock complete suppression of chronic nonmalignant pain. Also stated was “Evidence-based trials support the use of stronger opioids in recalcitrant chronic pain of arthritis. Thus we endeavor to better fulfill our Oath of Hippocrates: ‘to relieve pain and suffering’.

• 2002 An editorial by Rollin M. Gallagher (Pain Med March 2002;3(1):1-2) opines “We now justify using opioids for pain control, in the face of opiophobia, with the notion that uncontrolled pain has a more deleterious effect on functioning than do the opioids themselves [2]. The work of Zaczny and others, which is primarily based upon studies of persons with opioid addiction, not chronic pain, suggests that cognitive impairment is minimal on stable doses of opioids. Our collective clinical experience in pain medicine suggests that the benefits of pain relief from opioids, for example, helping someone to concentrate on the tasks of driving, to remain at work, or to sleep at night to avoid fatigue-related impairment or sedation, outweigh the risks that our medication will cause dangerous cognitive impairment or addiction”

• 2002 A study published on veterans use of opioids found that 33% of those with chronic pain were being prescribed opioids (J Pain Symptom Manage 2002 Feb;23(2):131-7)

• 2002 DA Marcus opined “When used appropriately and judiciously, opioid medications can be a useful addition to the treatment plan for patients with CNMP. Opioids can provide long-term, safe and cost-effective pain relief.” (Expert Opin Pharmacother 2002 Mar;3(3):229-35)

• 2002 A paper by Michael F Weaver and Sidney H Schnoll (J Pain Palliat Care Pharmacother 2002;16(3):5-26) suggested the way to distinguish between addiction and “pseudoaddiction” is to give “appropriate pain medication and observing the pattern of behavior”. They also suggested using long acting opioids with short acting opioids for “breakthrough pain”.

• 2002 DA Fishbain published a paper in Pain Medicine (2002 Jun;3(2):135-42) regarding allegations of breach of the standard of care when a patient with “alleged opioid addiction” was being tapered from opioids and during this time committed suicide. Expert witnesses could not rule out “pseudoaddiction”

• 2002 AAPM commercially supported events at the annual meeting included “Optimal Opioid Regimens for Chronic Pain: Optimal for Patients, Clinicians, and Caregivers” Supported by Janssen Pharmaceutica and “Drug Abuse, Diversion, and Its Effect on the Undertreatment of Pain” supported by Purdue Pharma LP

• 2002 Oxycontin sales increased nearly tenfold from 1997 to 2002 with 7.2 million prescriptions that year, 85% of which were for non-malignant pain. By 2002, Purdue had trained 2,500 physicians to speak to other physicians during luncheons and dinner meetings about Oxycontin in addition to having hosted 5,000 physicians, nurses and pharmacists in lavish conferences. At least 10% of active physicians in the US were being visited by Purdue representatives by 2002. Also during 2001 and 2002, Purdue sponsored 9 programs throughout the country to educate hospital physicians on how to comply with JCAHO’s pain standards for hospitals. Under an agreement with JCAHO, Purdue was the only drug company allowed to distribute certain educational videos and a book about pain management, and these materials were available for purchase from JCAHO’s website. By 2002, Purdue had sponsored 20,000 educational activities for physicians including many programs with co-sponsors the American Pain Society and the American Academy of Pain Medicine. Purdue was also a sponsor of the American Academy of Pain Medicine, the American Chronic Pain Association, the Dannemiller Memorial Education Foundation and American Academy of Physician Assistants. Purdue published an advertisement in the NEJM in May 2000 that stated Oxycontin could be used as the initial treatment for osteoarthritis pain. They also published an advertisement in JAMA in November 2002 that minimalized the risks and overstating the efficacy of Oxycontin, ads that were the subject of FDA warning letters in 2003.

• 2002 Joranson and Haddox co-authored a paper, warning state medical boards that fears of scrutiny by regulators, could possibly harm the efforts to manage pain in the US
 
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• 2003 Robert Kerns, PhD, John Otis PhD, Roberta Rosenberg, MS, and M. Carrington Reid PhD, MD, published an article that showed 50% of primary care patients in the VHA system experience significant regular pain and were concerned about the problem (J Rehabil Res Dev 2004 Sep-Oct;40(5):371-9)

• 2003 “Opioid therapy for chronic pain” was published by Jane Ballantyne and J Mao (N Eng J Med 2003 Nov 13;349(2):1943-53) discussing guidelines for use of opioids in chronic non-malignat pain.

• 2003 Mack Thomas concluded in Ochsner J 2003 Spring;5(2):15-21, “Pain has historically been under-treated. Opioid therapy by multiple routes of administration is legitimate medical therapy for the treatment of the chronic pain patient. The use of opioids for long-term pain control should be made available to chronic pain patients with adherence to recommended guidelines.”

• 2003 RN Jamison, JR Schein, S. Vallow, S. Ascher concluded opioids for chronic pain significantly improve psychomotor function in chronic pain patients (J. Pain Symptom Manage 2003 Oct 26(4):913-921)

• 2003 In Nursing Clinics of North America (2003 Sep;38(3):435-45), author AH Vallerand argues the administration of opioids to treat noncancer pain can be used and had become more acceptable. Also, the nurse has an important role in facilitating the conversion from short-acting to long acting opioids for chronic non-cancer pain, then individualization of therapy to determine which route and product best suits the patient’s needs and lifestyle. This article demonstrates nursing also encouraging the use of long acting opioids for around the clock administration

• 2003 Rollin Gallagher, MD, Douglas Weschules Pharm D published a paper (Pain Medicine Sept 2003;4(3);269-76) advocating for the use of methadone in hospice patients in the home care setting. “Although methadone may be a very useful opioid in the hospice setting, it is underutilized. Because of the very large cost differential between methadone and other long-acting opioids, underutilization of methadone has major cost-effectiveness repercussions for hospices utilizing fixed reimbursement rates”

• 2003-2012 Washington State steered doctors into prescribing very cheap methadone for Medicaid pain patients. The list of available (preferred) long acting drugs for these patients included only morphine and methadone. Because it was not well recognized that methadone has an exponential increase in side effects and respiratory depression with increased dosage (unlike other opioids), patients received much higher morphine equivalent dosages than doctors appreciated, with a massive increase in number of patients taking this medication used to treat addiction from heroin and high dose prescription opioids. By 2011, 31 states had methadone listed on the preferred list for pain treatment. (State pushes prescription painkiller methadone, saving millions but costing lives) The CDC published a report in 2017 that demonstrated states that listed methadone as a preferred drug had twice the overdose death rate of those that did not (MMWR Mar31 2017;66(12):320-323)

• 2003 Painedu.org was formed developing screening tools for substance abuse and opioid education tools called “Course-in-a-box” that are designed to promote opioid prescribing. This organization has been heavily supported by Endo Pharmaceutical.

• 2003 The Pain Relief Network was founded by the wife of a patient with connective tissue disease who lost access to high dose opioids/benzodiazepine combination when Dr. William Hurwitz was prosecuted by the US Government. It’s mission was to advocate for pain patients receiving opioids, claiming “We Have Someone Fighting For Us To Get Our Pain Medications” and stating chronic pain arising from under-treatment of patients recovering from surgeries and injuries is iatrogenic due to failure to supply enough opioids.

• 2003 VHA Pain Management Directive published designed to provide a system-wide VHA standard of care for pain management to reduce suffering, assure pain assessment performed in a consistent manner, assure pain treatment is prompt, and patients and families are included as active participants in pain management, implementation of Pain as the 5th Vital Sign, and development of web-based opioid training. An extensive organizational system was implemented with Rollin Gallagher, Bob Kerns, Matthew Bair, Michael Clark, Jack Rosenberg and others on the coordinating committee. Rosenberg was head of the Guidelines and Acute Pain Working Groups, Goodman Pharmacy Working Group, and Gallagher/Bair the Primary Care Working Groups.

• 2003 The DEA published as a press release on their main website “The Myth of the “Chilling Effect”, stating from 1999-2003 less than 0.1% of the one million registered doctors had sanctions pursued against them by the DEA, and that “Doctors Operating Within Bounds of Accepted Medical Practice Have Nothing to Fear From DEA”. Also in FY 2003, statistics were given showing there were 557 investigations of doctors, 441 actions taken against doctors (including voluntary surrender of license for cause in 324, 34 arrests, 22 letters of admonition, 21 administrative hearings, and 6 civil fines). News from DEA, News Releases, 10/30/03 Accessed Sept 2017

• 2004 Study by DA Marcus and RM Glick showing 2/3 of chronic pain patients in a 128 patient sample were taking Oxycontin more than twice a day. Breakthrough medications were used in 47% of those with twice a day dosing and 21% of those with more than twice a day dosing. (Clin J Pain 2004 Sep-Oct;20(5):363-6)

• 2004 Randall Brown, C Kraus, M Fleming, and S Reddy published a paper (Postgrad Med J 2004;80(949):654-9 that discussed methadone use in chronic pain. Among their statements, “Though not generally a first line agent, methadone may be considered early on in the treatment of neuropathic pain and/ or in situations where cost issues are compelling” and “…methadone also provides effective analgesia. Patients who experience inadequate pain relief or intolerable side effects with other opioids or who suffer from neuropathic pain may benefit from a transition to methadone as their analgesic agent.”

• 2004 TE Dews and Nagy Mekhail from the Cleveland Clinic published an article Safe use of opioids in chronic noncancer pain (Cleve Clin J Med 2004 Nov;71(11):897-904) that stated “Many physicians avoid prescribing opioid analgesics for chronic pain because of misconceptions or fears about efficacy, adverse effects, abuse, and addiction potential”

• 2004 In a journal article entitled “Myths and facts about long-acting opioids in chronic pain: a multidisciplinary analysis” published in ONS News 2004;19(9 Suppl):5506), a nursing journal, it was argued “Opioid analgesics have well-established efficacy in controlling chronic pain” and improving function. “Despite this, these agents continue to be underused in patients with moderate to severe pain who require almost continuous pain relief”.

• 2004 Steve Passik opined (CNS Drugs 2004;18(1):13-25) that complex behaviors in patients with a prior history of substance abuse may either be due to addiction or may be simply a reaction to under-medicated pain, and that control over prescriptions may be accomplished without terminating opioid prescribing.

• 2004 Palladone (extended release hydromorphone) approved but was discontinued in 2005 after the FDA discovered taking it with alcohol would cause instantaneous release of all of the active drug

• 2004 The Federation of State Medical Boards (FSMB) guidelines for opioid prescribing were modified, suggesting disciplinary action by the state medical board for physicians who did not adequately treat pain.

• 2004 International Association for the Study of Pain (IASP) launched an initiative with the motto: “Relief of Pain Should Be Human Right”

• 2004 The American Academy of Pain Medicine, American Pain Society, and the American Society of Addiction Medicine created and officially adopted a consensus document, Public Policy Statement on the Rights and Responsibilities of Health Care Professionals in the use of Opioids for the Treatment of Pain. This is the official policy of the three organizations, and was ratified by all three boards in March and April 2004. It was prepared by committee members Seddon Savage MD (chair)-APS, Edward C. Covington, MD-AAPM, Aaron Gilson PhD-APS, Doug Gourlay-ASAM, Howard Heit MD-ASAM, and John B. Hunt MD-AAPM Among its eight statements: “Opioids should be prescribed in a lawful and clinically sound manner. Providers who are practicing medicine in good faith and who use reasonable medical judgment regarding the prescription of opioids for the treatment of pain should not be held responsible for the willful and deceptive behavior of patients who successfully obtain opioids for non-medical purposes. It is the appropriate role of the DEA and other regulatory agencies to inform physicians of the behavior of such patients when it is detected. It also affirmed legal and licensing actions as appropriate when taken against health care providers who are complicit in the diversion of scheduled drugs, illegal prescribing, consistently fail to recognize addictive disorders/medication misuse/diversion. Initial decision-making and ongoing management should be documented, patients followed at reasonable intervals, and therapy revised. Regulatory, legal, quality assurance reviews must be made in context of the individual case and performed by persons with a requisite level of understanding of pain medicine.” https://www.asam.org/docs/default-s...oid-rights-consensus-format-4-04.pdf?sfvrsn=0 Accessed September 2017

• 2004 A series called “Dear DEA” published in Pain Medicine (Sept 2004;5(3):303-308) and in August 2004 on the DEA drug diversion (www.deadiversion.usdoj.gov) official website, as a series of frequently asked questions (FAQs) being posed to the DEA by identified physicians including Edward Covington, MD. These FAQ were published with much fanfare, including a ceremonious press conference hosted by the DEA that resulted in widespread national media coverage. The responses provided in the FAQ were by Patricia Good, Chief Liaison and Policy Section Office of Diversion Control of the DEA and represented the results of 4 years of negotiations between pain management groups led by David E. Joranson of the University of Wisconsin Madison Medical School Pain and Policy Studies Group, the AAPM, and also with Dr. Russell Portenoy. These FAQ published were supposed to ease doctors fear of being prosecuted by the DEA for drug diversion by helping doctors understand the position of the DEA on the nuances of opioid prescribing. The first FAQ was the legality of writing multiple prescriptions for opioids on the same day to be filled in the future with a “Do Not Dispense Until __ date instruction to the pharmacist. The DEA concurred this practice is legal. The second: Can I prescribe opioid Analgesia to a Patient in a Methadone Clinic? The DEA concluded it is not illegal to treat a chronic pain patient also being seen in a methadone clinic. Third: Is it legal to wean patients from opioids using methadone? The DEA responded “This is not considered “detoxification” as that term is applied to addiction treatment, therefore it is legal to use methadone to wean patients from opioids being used for pain.” Forth: Is it legal to use Suboxone or buprenorphine for pain control? DEA answer was yes, without a data 2000 number. Fifth: Can I use an opioid agonist as a temporary substitute for Suboxone/Subutex in a patient requiring elective surgery? The DEA responded in the affirmative. The FAQ also concluded the number of tablets patients receive, the number of patients in a doctor’s practice, and how long the therapy lasts “do not, by themselves indicate a problem”. In October, 2004, the physician William Hurwitz was being prosecuted by the DEA, and the FAQ were introduced as evidence by the defense. With an imminent trial of Hurwitz forthcoming and fear the FAQs would be used against the DEA, the FAQs were suddenly removed from their website in August 2004, and the DEA then adopted the rather farcical explanation the FAQ guidelines were never “official” since they had not been published in the Federal Register, and the DEA denied the removal of the FAQ had anything to do with Dr. Hurwitz.. By November 2004, the DEA had updated their website with an “Interim Policy” that effectively said the opposite of the published FAQs on four points listed above, and it wasn’t until much later the FDA clarified its position on such important items as multiple scripts being written at one setting, leaving pain patients and doctors in limbo for over a year. The judge threw out the initial FAQ that had been admitted into evidence after the DEA led by Karen Tandy, pulled them from their website. A firestorm of protests ensued with the letters to the court written by past presidents of the APS, and the sudden withdrawal and 180 degree change in DEA policy was opposed by the AAPM, American College of Physicians, the Association of American Physicians and Surgeons, and the Pain and Policy Study Group of the University of Wisconsin. Furthermore, the DEA’s new policy criminalized the practices being taught in pain medicine programs (American Medical News Dec 20, 2004)

• 2005 A journal article by K Auret and SA Schug entitled “Underutilisation of opioids in elderly patients with chronic pain: approaches to correcting the problem” stated “Underutilisation of opioids is a major component of poor pain management in this group of patients, despite good evidence for the effectiveness of opioids”. Reasons for this include “opiophobia, fear of polypharmacy, avoidance of opioids because of concerns about tolerance, physical dependence, addiction and adverse effects.” The review presented methods of overcoming the “barriers” to opioid prescribing above. (Drugs Aging 2005;22(8):641-54)

• 2005 An article by James Toombs entitled “Methadone treatment for pain states” published in American Family Physician (Am Fam Physician 2005 Apr 1;71(7);1353-8 it was stated “methadone may be prescribed by licensed family physicians for analgesia, may be an appropriate replacement for opioids when side effects have limited further dosage escalation, and methadone is less expensive than other sustained-release opioid formulations. It was also stated “its use in opioid naïve patients may have some benefits”

• 2005 ME Lynch published a paper reviewing the use of methadone for chronic noncancer pain (Pain Res Manag 2005 Autumn;10(3):133-44) and states methadone is “a very attractive option for the treatment of chronic pain”. The author goes on to extoll the virtues of the drug as a chronic pain medication.

• 2005 A paper entitled “A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Pilot Study to Assess the Effects of Long-Term Opioid Drug Consumption and Subsequent Abstinence in Chronic Noncancer Pain Patients Receiving Controlled-Release Morphine” was published (Pain Medicine March 2006;6(2):113-21) by David Cowen PhD, Jenifer Wilson-Marnett PhD, Peter Griffiths PhD, David J.A. Vaughan MBBS, Anjalee Gondhia, MBBS, and Laurie Allan MBBS. This paper followed ten patients taking low-moderate dose (average 40mg/day) morphine for an average of 2 years, then a placebo was substituted for morphine with their knowledge for 60 hour periods. 30% had opioid withdrawal symptoms, the pain intensity increased, and there were detrimental effects on sleep, mood, activity, and enjoyment of life. There were no psychological dependence or drug cravings. Their conclusion was there exists a group of chronic non-cancer pain patients whose long-term opioid consumption can be beneficial and remain moderate without them suffering from the consequences of problematic opioid drug use or addiction.

• 2005 Scott Fishman, MD became president of the American Academy of Pain Medicine

• 2006 Fentora FDA approved (Cephalon) for the treatment of breakthrough pain in opioid tolerant cancer patients in 100,200, 300, 400, 600, and 800mcg units with a Cmax 60% higher than that of Actiq of the same dosage and Tmax 46min compared to 91 min for Actiq. In less than one year, patient overdoses and deaths were reported to the FDA

• 2006 Opana ER FDA approved (Endo)

• 2006 The Federal Government CMS (Medicare & Medicaid) launched a patient satisfaction survey for hospitals that contained three questions on pain management satisfaction. This survey, Hospital Consumer Assessment of Healthcare Providers and Systems survey (HCACPS) was used to financially reward or penalize hospitals. This data is reported online and has been a significant force in promoting opioid prescribing by physicians, especially since there was a rapidly increase in the percent of doctors employed by hospitals shortly thereafter. The pain management questions will be discontinued as part of the formula to penalize physicians financially in 2018

• 2007 Lynn Webster MD, one of the leading voices in pain management, states in his book “Avoiding Opioid Abuse While Managing Pain- Guide for Practitioners” that opioids had a low risk of addiction, less than 1%. Also, “Opioids offer safe, effective treatment for many chronic pain conditions and pose little risk of addition for most patients who take them to control pain. However, some patients treated with opioids do display behaviors consistent with addiction.” Ultimately he was investigated by the DEA for causing up to 20 deaths of patients

• 2007 Purdue Pharma admitted under Federal prosecution that it had misled doctors into thinking Oxycontin was less addictive and less easily abused than other drugs in its class and agreed to pay more than $600,000,000 in fines and fees to the Justice Department. In addition their chief exexutives pled guilty to misbranding. The president of Purdue Pharma Michael Friedman paid 19 million in fines, and their top lawyer Howard R. Udell paid 8 million dollars in fines, and Dr. Paul D. Goldenheim the former medical director paid 7.5 million dollars although Purdue stated none of these individuals engaged in nor tolerated the misconduct at issue in the investigation, and to the contrary, took steps to prevent any misstatements in the marketing or promotion of Oxycontin and to correct any such misstatements.

• 2007 Fentora approved. Within one year, deaths were reported to the FDA due to opioid intolerant patients receiving the medication or mg to mg substitution for Actiq by physicians and pharmacists (Fentora has 65% bioavailability, Actiq is 48%). Cmax of Fentora is more than 50% higher than Actiq and the AUC 0-max is nearly 300% higher for Fentora.
 
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Very interesting podcast on NPR right now on the Sackler family. Brothers made hundreds of millions off of pushing Vallium as a cure all for “psychic tension” back in the 40’s. Went on to start Purdue pharma and single handedly changed the medical culture on how we view and prescribe Oxyxontjn/opioids; went on to make billions.
Now they are a huge philanthropy family and one of the richest families in the country. Their name is on hundreds of libraries, museums etc but you wont find their name on any recovery centers... Their name needs to be floated around more so they are pressured into doing more for the epidemic that they started.
 
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