Chronic Pain Treatment With Opioid Analgesics

Benefits versus Harms of Long-term Therapy

Nalini Sehgal; James Colson; Howard S Smith


Expert Rev Neurother. 2013;13(11):1201-1220. 

In This Article


CNCP treatments are far from optimal. As a result, many CNCP patients experience poorly controlled pain and its deleterious effects for years. Ideally, effective treatment for CNCP should provide clinically significant pain relief that is sustained over years and improves physical activity, sleep, mood and QoL in the majority of cases. The burden of treatment related adverse effects should be small so that compliance with treatment remains high. Judging by these criteria, it is obvious that opioid therapy for CNCP is not a universal success. Controlled clinical trials show that 50–70% patients with CNCP fail opioid therapy. Those who respond, report mild to moderate reduction in pain intensity for a short term. There is no controlled study on opioid efficacy which is longer than 16 weeks in duration. In practice, long-term efficacy is extrapolated from short duration studies, which is obviously problematic and misleading. Uncontrolled prospective studies with follow-up intervals of 6–24 months, show that majority of patients who initially respond to opioids ultimately abandon treatment, either due to declining efficacy or troublesome side effects. The evidence on functional status is even less convincing: there is a lack of studies showing that opioids improve physical activity, function, sleep, mood or QoL. Very few studies have measured functional outcomes and those that do, vary in the selection of specific outcomes and assessment tools. There is no evidence that opioids decrease depression, anxiety, physical disability or increase return to work rates among disabled CNCP patients. There is a high prevalence of depression and anxiety in CNCP patients, and patients with psychiatric comorbidity are more likely to receive opioids. Yet such patients are excluded from opioid efficacy randomized clinical trials. Hence, the results of such trials lack generalizability to the majority of CNCP population. Opioid therapy is also associated with multiple side effects, and 80% patients experience more than one side effect. Among these, constipation is particularly troublesome and can become a serious problem for some patients. Endocrine disturbances, reported previously in heroin addicts, are not rare in CNCP patients on long-acting opioids. Furthermore, opioid therapy is not free from risk of addiction, as was once believed. CP patients with psychiatric comorbidity and personal or family history of current or past substance abuse are at increased risk for opioid misuse. Opioid misuse, abuse, overdose and unintentional death rates have trended upwards with liberal use of opioids in past two decades. Opioid related mortality rates are dose dependent, the rates increase manifold at higher doses. Although there is no consensus yet on an upper dose limit for opioids, studies suggest an optimal balance, where the benefits outweigh risk is achieved at doses of <100 mg/day MED.

So, 'do the benefits of opioid therapy outweigh the risks in CNCP?' Current evidence suggests that a balance, where the greatest amount of pain and related suffering is mitigated and there is the least amount of opioid related adverse effects, is difficult to achieve in the vast majority of CNCP patients. At the same time, there is a need to be mindful of the widespread and adverse consequences of poorly managed pain itself. Therefore, opioids should be considered only when pain is severe and other non-opioid therapies fail to adequately control pain. A structured approach that includes a bio-psychosocial evaluation should be employed when considering initiation or continuation of opioid therapy for a patient with chronic nonterminal pain. Opioids should be prescribed on a trial basis, and continued only if progress toward functional goals is demonstrated. Proper patient screening, education and preemptive treatment of potential side effects may aid in maximizing effectiveness while reducing the severity of side effects and adverse events. Specialist consultation should be sought for patients on high doses, and with complex psychiatric and social issues. Identifying patients who are more likely to respond to long-term opioid therapy is a challenge. There is currently no well-validated objective means of accurately identifying patients likely to experience good analgesia with low side effects and abuse risk prior to initiating opioid therapy.[137] In general, a patient with stable psychosocial status and nociceptive pain, responsive to low to moderate doses of opioids, has a greater chance of success with long-term opioid therapy than a patient with a complex and unstable psychosocial background and neuropathic pain only partly relieved by high doses of potent opioid analgesics. In addition, treatment in a multidisciplinary setting versus solo practise improves compliance and decreases risk of abuse and complications. The evidence for this type of pain management is however meager and studies that compare treatment outcomes in multidisciplinary versus single modality treatments are needed. Presently, a 'trial and error' method is employed to identify patients with opioid responsive pain. Such an approach is costly, time consuming and inefficient and needs to be replaced by objective bedside clinical or laboratory tests that can reliably prognosticate treatment response to opioids. Research on drug development should direct, efforts at discovering drugs that retain the analgesic potency of opioids without their addictive potential. Drugs that bind to opioid receptors in the inflamed or injured tissues or PNS and do not enter the CNS, may be associated with lower risk of adverse effects and lower abuse potential. Finally, there is need for a research strategy to study long-term opioid effectiveness, identify and quantify adverse effects and improve evidence generation methodology.[140]