Alternatives to Opioids in the Pharmacologic Management of Chronic Pain Syndromes

A Narrative Review of Randomized, Controlled, and Blinded Clinical Trials

Nicol, Andrea L. MD, MSc; Hurley, Robert W. MD, PhD; Benzon, Honorio T. MD


Anesth Analg. 2017;125(5):1682-1703. 

In This Article

Abstract and Introduction


Chronic pain exerts a tremendous burden on individuals and societies. If one views chronic pain as a single disease entity, then it is the most common and costly medical condition. At present, medical professionals who treat patients in chronic pain are recommended to provide comprehensive and multidisciplinary treatments, which may include pharmacotherapy. Many providers use nonopioid medications to treat chronic pain; however, for some patients, opioid analgesics are the exclusive treatment of chronic pain. However, there is currently an epidemic of opioid use in the United States, and recent guidelines from the Centers for Disease Control (CDC) have recommended that the use of opioids for nonmalignant chronic pain be used only in certain circumstances. The goal of this review was to report the current body of evidence-based medicine gained from prospective, randomized-controlled, blinded studies on the use of nonopioid analgesics for the most common noncancer chronic pain conditions. A total of 9566 studies were obtained during literature searches, and 271 of these met inclusion for this review. Overall, while many nonopioid analgesics have been found to be effective in reducing pain for many chronic pain conditions, it is evident that the number of high-quality studies is lacking, and the effect sizes noted in many studies are not considered to be clinically significant despite statistical significance. More research is needed to determine effective and mechanism-based treatments for the chronic pain syndromes discussed in this review. Utilization of rigorous and homogeneous research methodology would likely allow for better consistency and reproducibility, which is of utmost importance in guiding evidence-based care.


It is estimated that more than 100 million Americans spend each day in chronic pain, at a yearly cost of more than $600 billion in lost productivity and health care expenditures.[1] A central theme outlined in a 2011 Institute of Medicine report was that despite the care of chronic pain patients being extremely costly, outcomes continue to remain relatively poor.[1] Currently, physicians who treat patients in chronic pain are advised to provide comprehensive and multidisciplinary treatments. A multidisciplinary pain strategy typically includes physical therapies, psychological care, and pharmacologic management. Pharmacologic therapies are typically aimed at treating the underlying pathophysiologic mechanisms or are simply used for symptom-based treatment. Many practitioners rely on nonopioid medications to treat chronic pain; however, for some patients, opioid analgesics are utilized for the symptomatic treatment of chronic pain.

In 2016, in response to the increasing rates of opioid prescribing coupled with an epidemic of opioid use disorders in the United States, the Centers for Disease Control (CDC) published guidelines on the use of opioid analgesics for chronic nonmalignant pain.[2] Opioid prescriptions increased per capita by 7.3% from 2007 to 2012, and in 2012 alone, 259 million prescriptions for opioid pain medications were written, enough for every adult in the United States to have a bottle of opioid medications.[3,4] Evidence from the literature supports short-term efficacy of opioids for reducing pain and improving function in some pain conditions, but there is a paucity of evidence that suggests long-term benefits of opioids for chronic pain.[5]

The first recommendation of the CDC guidelines is that nonpharmacologic and nonopioid pharmacologic therapy is preferred for chronic pain and should be tried first.[2] Nonopioid pharmacotherapy includes, but is not limited to, acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), amine reuptake inhibitors (ARIs), and membrane stabilizers. The goals of this review are to provide the reader with data from prospective, randomized, controlled, and blinded clinical trials in which nonopioid medications were investigated for the treatment of chronic pain.