An alternative approach to solving the opioid epidemic: is there a role for non-pharmacologic analgesic therapies?

KEYWORDS:

• Opioid epidemic
• multimodal analgesic therapies
• alternative non-pharmacologic analgesic therapies

In 2007, a review article [1] by international experts in pain management encouraged the more widespread use of opioid-containing analgesics by suggesting that ‘if only we [physicians and nurses] could overcome our “opiophobia,” we would improve pain management.’ In an accompanying editorial, we argued that ‘less may be more’ with respect to the use of opioid (narcotic) analgesics [2] and that using non-opioid analgesics to reduce the dependence on oral and parenteral opioid analgesics would reduce the risk of opioid-related side effects, including nausea, vomiting, constipation, ileus, bladder dysfunction, pruritis, sedation, hallucinations, ventilatory depression, as well as long-term physical dependence and addiction liability. Even short-term use of potent opioid analgesics during the intraoperative period can actually aggravate pain due to opioid-induced hyperalgesia (i.e. acute tolerance) [3,4]. Although opioids are highly effective in providing short-term relief of acute pain, they do not treat the underlying disease process. In fact, recent retrospective studies suggested an association between the use of large doses of opioid analgesic medication during the perioperative period in patients undergoing primary cancer surgery and increased cancer recurrence rates [5].

In 2014, 16,790 deaths were reported in the USA secondary to overdosing with prescription opioids. Recently, the Centers for Disease Control and Prevention (CDCP) conducted a review of the benefits and harms, values and preferences, and costs of opioid use for chronic pain [6]. These authors concluded that long-term opioid use was associated with increased risks of opioid use disorder, overdose, and death, and studies have failed to demonstrate any long-term (≥1 year) benefits. In an epidemiological study by Eriksen et al. [7] involving chronic pain patients treated with opioids for 5 years, these investigators provided compelling evidence that opioids were not a panacea for chronic pain. In fact, the patients’ quality of life failed to improve despite escalating doses of opioids over the 5-year study period. These authors concluded that ‘it is remarkable that opioid treatment of long-term chronic non-cancer pain does not seem to fulfill any of the key outcome treatment goals, namely, pain relief, improved quality of life and improved functional capacity.’ Furthermore, opioid analgesic therapy aimed at alleviating chronic pain may actually aggravate the situation due to opioid-induced hyperalgesia [3,4].

In excess of 10 million people in the United States were reportedly using prescription opioids for nonmedical reasons in 2014, and 2.1 million people met diagnostic criteria for a substance use disorder involving prescription opioids [8]. This was the highest number of individuals considered to have an opioid addiction since the late nineteenth century. According to the US Surgeon General, despite spending in excess of $35 billion on rehabilitation programs for opioid-dependent patients in this country, only 10% of patients with a substance abuse problem involving opioid-containing medications are receiving treatment [9]. Pharmaceutical companies manufacturing opioid medications (and allied groups [e.g. Pain Care Forum]) spent more than $880 million in 2015–2016 on campaign contributions to lobby politicians at the state and federal government level to block legislation aimed at curtailing the use of opioid analgesics. Although heroin use in this country declined in the 1990s as prescription opioid use soared, its use is resurging as prescription opioids are becoming more difficult to obtain and black-market drugs like heroin and the newer fentanyl analogs are less costly and easier to obtain. Currently, four out of five individuals initiating heroin use report starting with a prescription opioid. Sadly, the public is now paying a huge price for ignoring the early warnings regarding risk of more widespread opioid use for acute and chronic pain management. Recent articles from the CDC have recommended increasing use of non-opioid and non-pharmacologic approaches (e.g. cognitive behavioral therapy, acupuncture, and physical therapy) in the management of chronic pain [6,8].

The ‘liberalization’ of opioid use for acute and chronic pain management [1] and the institution of pain ‘as a fifth vital sign’ [10,11] have led to more aggressive use of opioid analgesics in the medical community. The fifth vital sign utilizes a simple 11-point verbal numerical pain scoring system (0 = no pain to 10 = intolerable pain) and is now a mandatory part of the clinical assessment of pain by many health-care organizations in the USA. Interestingly, routinely measuring pain as the fifth vital sign has produced inconsistent effects in improving the quality of pain management [10,11]. However, this controversial clinical practice has led to an increase in the average dosages of opioid analgesic medication administered to hospitalized patients and increased the incidence of adverse drug reactions (e.g. opioid ‘over sedation’) [11] and in-hospital opioid overdoses and opioid-related deaths after major elective surgery procedures [12]. Of the patients experiencing life-threatening adverse reactions to opioid analgesics (e.g. respiratory and/or cardiac arrests), >90% had a documented decrease in their level of consciousness preceding the event [10]. Concomitant use of sedative–hypnotic and gabapentinoid drugs contributes to the increase in opioid-induced sedation. In addition, use of an opioid infusion after surgery increases the risk of opioid overdosing without reducing postoperative pain scores, the number of nocturnal awakenings, or opioid-related side effects compared to traditional intermittent bolus dosing of opioid drugs [13]. Use of continuous infusions is ‘outside the norm’ and not a best practice outside of the context of patients with acute pain who have underlying chronic pain requiring high doses of opioid analgesics. On the other hand, the adjunctive use of non-opioid analgesics like ketorolac (a potent parenteral non-steroidal anti-inflammatory drug [NSAID]) and celecoxib can significantly reduce the opioid requirement and opioid-related adverse reactions during the postoperative period and facilitate the recovery process [14,15]. Unfortunately, misinformation regarding the bleeding risk and other side effects associated with the short-term use of NSAIDs (and COX-2 inhibitors) has made some physicians reluctant to administer these valuable analgesic adjuvants during the perioperative period.

The annual number of overdose deaths involving prescription opioids has nearly quadrupled since 2000, and this increase parallels the marked growth in the quantity of opioid pain relievers being prescribed for the treatment of acute and chronic pain [16]. One in every five cancer patients is ‘at risk’ for opioid use disorder. Prescription opioid addiction and misuse have not only contributed to a resurgence in heroin use, but also the spread of HIV and hepatitis C [17]. It should be acknowledged that the opioid epidemic stems not only from the aggressive marketing policies of drug manufacturers (and distributors), but also from a lack of effective educational programs for medical providers regarding safe opioid prescriptive practices (e.g. use of opioid risk screening, urine drug testing, pain management agreements, and effective multidisciplinary non-opioid analgesic treatment modalities). In a recent publication from the CDCP [6], it was reported that patients initially given a one-day supply of opioid medication had a 6% likelihood of still using the drug a year later. However, that number rose to roughly 10% for patients given a two-day supply and 45% for patients given a 40-day prescription.

In a call to action to end the opioid epidemic in this country [18], the US Surgeon General recommended that physicians follow the CDCP guidelines in prescribing opioids for chronic pain. However, a recent report suggested that less than 60% of physicians were utilizing these guidelines for the treatment of chronic pain [19]. In the Surgeon General’s ‘Turn the Tide’ Rx Pocket card (which was mailed to 2.3 million clinicians in this country), there were no recommendations regarding the use of non-pharmacologic analgesic therapies for treating chronic pain despite compelling evidence in the peer-reviewed literature that they can be extremely useful adjuvants for treating a wide variety of acute and chronic pain conditions. In the recent FDA response to the opioid crisis, Califf et al. [20] emphasized that more alternatives to opioid analgesics are clearly needed, including non-pharmacologic treatments. According to these authors, ‘non-pharmacologic approaches to pain treatment were identified as an urgent priority.’ Yet, the main emphasis appears to be on developing a new ‘magic bullet’ drug that will produce opioid-like analgesia without side effects and dependency [21].

Alternative pain therapies like traditional Chinese acupuncture have been used to treat pain for centuries. However, the use of acupuncture and non-pharmacologic electro-analgesic, as well as cold laser therapy, techniques have failed to gain widespread acceptance in the medical community despite numerous clinical studies documenting their analgesic efficacy [22,23] and superiority compared to physical therapy alone [23,24]. The government and the health-care industry (e.g. third party payers) discourage the use of these ‘alternative’ analgesic therapies by refusing to provide adequate reimbursement to health-care providers of non-traditional treatments (e.g. acupuncture, laser therapy, mindfulness, and other psychotherapeutic modalities). Prescribing an opioid medication is clearly a more time-efficient way of getting patients out of the primary care provider’s office in the narrow 15–20-min window allowed for follow-up appointments. Electro-analgesic techniques (including acupuncture) provide effective short-term pain relief; however, these treatments are much more labor-intensive than utilizing non-invasive laser therapy or simply writing opioid prescriptions for physicians. Both low-level laser therapy (LLLT) and high-intensity laser therapy (HILT) can be administered by a technician using a simple ‘point-and-shoot’ technique and provides longer lasting analgesic effects than electro-analgesia for treating acute and chronic pain [23]. When directly compared to LLLT, clinical studies suggest that the use of HILT provides more effective pain relief [23]. In a pilot study involving a powerful high-intensity laser device (Phoenix Thera-lase [Dallas, TX]), patients who had become addicted to prescription opioid-analgesic medication after undergoing major surgical procedures were successfully treated with HILT [25]. A more recent report also described the successful use of HILT to treat a woman with drug-resistant fibromyalgia [26]. This patient was able to discontinue her use of opioid analgesic medications. Preliminary studies have also demonstrated the benefits of HILT in patients with long-standing pain due to a variety of degenerative joint diseases [27]. Clearly, additional larger-scale clinical studies utilizing these non-traditional treatment modalities are needed in patients with opioid abuse disorders. However, given the limited success with existing opioid treatment programs (including physical therapy), physicians and nurses should seriously consider incorporating both non-opioid and non-pharmacologic analgesic therapies as part of the treatment plan for persistent post-surgical and chronic pain [28].

The growing importance of opioid dependency after surgical procedures has been emphasized in recent articles by Goesling et al. [29] and others [30–34]. These investigators reported that prescription opioid analgesic use often continued after joint replacement surgery despite the fact that the patients were no longer experiencing pain in the operated joint. In addition to joint replacement and spinal fusion surgery, cesarean delivery was surprisingly reported to be associated with a high incidence of opioid-naive patients discharged on large doses of opioids (Ray ND, Annual meeting of the American Society of Anesthesiologists, 2017). The long-standing surgical practice of giving all postoperative patients a prescription for opioids medication at the time of discharge from the hospital has clearly contributed to the opioid abuse problem. Compared to countries where this is not a standard practice, nearly 6% of the US population aged 15–64 was reportedly abusing opioids in 2015 (vs. <1% for these other countries) [31]. In a retrospective study involving over 390,000 outpatients over the age of 66 years who had undergone minor ambulatory surgery procedures, Alam and colleagues [32] reported that opioid-naive patients >66 years receiving an opioid analgesic medication within 7 days after undergoing a minor surgical procedure were 44% more likely to continue using opioids one year after the operation. In patients >66 yeas undergoing surgery for head and neck cancer, 33% developed persistent opioid use lasting >90 days [33]. Not surprisingly, the incidence was higher in previous opioid users (48% vs. 18.5% in opioid-naive patients).

Data supporting an association between perioperative opioid use and subsequent chronic postoperative opioid use are accumulating. Recently, it was reported that there is an ~6% incidence of new persistent opioid use after elective surgery, and it was similar after both major and minor surgical procedures [30]. The factors associated with increased risk of prolonged postoperative opioid use after surgery included younger age, lower income, diabetes and chronic use of benzodiazepines and antidepressant drugs, and behavioral and pain disorders [34,35]. Additional risk factors for chronic opioid use after surgery include male sex, history of drug or alcohol abuse, use of benzodiazepines and antidepressant drugs, and patients undergoing major arthroplasty procedures [35]. Opioid use prior to surgery is independently associated with increased morbidity and postoperative health-care costs [36]. It was recently reported that patients with a history of opioid abuse or dependence undergoing major surgical procedures had higher 30-day readmission rates (11% vs. 9%), longer mean hospital lengths of stay at initial admission (6 vs. 4 days), higher estimated hospital costs during initial admission ($18,528 vs. $16,617), and longer length of stay following a readmission (6 vs. 5 days) [37].

Recent articles in the lay press have discussed an allegedly ‘new paradigm for treating opioid addiction’ which involves giving Suboxone (a combination of buprenorphine [a partial opioid agonist] and naloxone [an opioid antagonist]). The use of novel combinations of opioid-containing compounds, including agonists and partial agonists, to treat acute and chronic pain, as well as opioid dependency, is a predictable ‘solution’ to the opioid epidemic by the pharmaceutical industry (and their lobbyists in Washington DC). Unfortunately, repeating the same pharmacologic (opioid)-based approach to managing pain and expecting a different result is the very definition of insanity and will not solve the current opioid crisis. Of importance, Barnett et al. [38] reported in a recent issue of the New England Journal of Medicine that long-term opioid use was increased in previously opioid-naive patients who received treatment in an emergency department from high (vs. low)-intensity opioid prescribers. Altering the prescribing habits of physicians and their surrogates to emphasize the role of non-opioid analgesic drugs and innovative non-pharmacologic approaches for treating acute and chronic pain would be an important first step in controlling the current opioid crisis [28,39].

Hopefully, the medical community will wake up to the fact that ‘simply giving more opioid medication’ is not the solution to the current crisis in this country, it is simply adding fuel to the fire! In the new clinical practice guidelines for the management of back pain [40], the Clinical Guidelines Committee of the American College of Physicians endorsed the use of non-invasive non-pharmacologic treatments for treatment of acute, subacute, and chronic low back pain. As suggested in our editorial on the perioperative use of opioid analgesics more than a decade ago, encouraging more liberal use of opioid analgesics in acute and chronic pain management (as well as in hospice care) has directly contributed to the current opioid abuse problem [2]. Changing the opioid prescribing practices after elective surgery and in emergency departments which have contributed to persistent opioid use and abuse is an easy first step in controlling the widespread abuse of opioid medication [31,38,39]. Finally, utilizing an integrative (inter-disciplinary) approach to pain management [41,42] involving more aggressive use of non-opioid analgesics, physical- and psychological-based therapies, as well as novel innovative non-pharmacologic complementary and ‘alternative’ therapies (e.g. HILT) to achieve acute and chronic pain control would likely be a more cost-effective approach to dealing with the current opioid epidemic in this country. Clearly additional well-controlled clinical studies are needed to support the use of alternative ‘outside of the box’ approaches to managing pain in opioid-dependent patients.

In summary, despite the introduction of CDC guidelines for the management of acute perioperative pain and chronic non-cancer pain in 2016, the use and abuse of opioid analgesic drugs for the treatment of acute and chronic pain has continued to increase in the USA. Although newer practice guidelines and prescription monitoring programs have led to reductions in opioid prescribing patterns, the opioid abuse problem remains a national health-care concern because millions of Americans are still using prescription opioid analgesic for non-medical reasons. The pharmaceutical industry continues to promote newer opioid formulations for treating post-surgical and chronic pain, and the current pharmaceutical market for ‘add on’ drugs to treat opioid-related side effects actually exceeds the sales of opioid analgesics. More importantly, prescription oral opioid analgesics are a gateway to other more dangerous drugs of abuse (e.g. black-market fentanyl analogs, heroin), which are directly responsible for the rapidly rising number of deaths due to overdosing and increasing the cost to the health-care system for the emergency treatment of opioid-related complications. Until health-care providers understand that opioids do not cure disease and stop the widespread practice of routinely prescribing these highly addictive substances after surgery and for managing chronic and prolonged postsurgical pain, the opioid abuse epidemic will continue grow. Attempts to curb the current drug abuse crisis by developing novel opioid-related drugs have primarily served to benefit the pharmaceutical industry and their drug distributors. Physicians, as well as nurse practitioners, need to utilize multimodal (‘balanced’) analgesic therapies, including non-pharmacologic ‘alternative’ therapies, as part of an interdisciplinary integrative approach to managing acute and chronic pain in the future.

Declaration of interest

P White has received research grants and consulting fees from pharmaceutical companies (e.g., Merck, Pfizer, Astra-Zeneca, Pacira) which manufacturer non-steroidal anti-inflammatory drugs and local anesthetics. P White is a consultant for Neumentum, Inc. (Palo Alto, CA) which is developing a novel ketorolac drug delivery system, and a consultant for Amphastar Pharmaceuticals (Rancho Cucamunga, CA) which manufacturers the generic opioid-reversal drug naloxone. P White is also a consultant to Phoenix Thera-lase Systems, Inc. (Dallas, TX) which manufactures a high-intensity laser for acute and chronic pain therapy. PGM peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

None reported.

Additional information

Funding

This editorial was invited and not funded; however, P White is supported by White Mountain Institute, a private not-for-profit foundation.