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Benefit of Long-acting Versus Short-acting Opioids?

Ask the Expert May 2014

Question: Is there a benefit to using long-acting versus short-acting opioids for chronic pain?

Answer: When considering whether to treat a patient with an opioid for chronic pain, clinicians can select from several different formulations on the market, including immediate-release, extended release, controlled-release, and sustained-release options. Generally, these agents can be divided into 2 categories: short-acting (immediate-release) and long-acting (extended-release, controlled-release, and sustained-release) opioids.1

Therapeutic benefits of long-acting opioids (LAOs) over short-acting opioids (SAOs) include decreased dosing frequency and consistent, sustained analgesia. Additionally, the pharmacokinetic profiles of LAOs provide the advantages of steady plasma concentrations, decreased “end-of-dose failure,” and reduced frequency of sleep disturbances, nausea, pruritus, and constipation. Finally, the patient may have better adherence if the drug is dosed less frequently.1 A common generalization holds that patients on chronic opioid therapy (COT) should use a long-acting opioid for around-the-clock pain control, with a short-acting opioid for breakthrough pain if needed.2 But considering the availability of several different treatment options and the overall subjectivity of pain perception, some clinicians have questioned whether LAOs and/or SAOs are the best treatment approach for chronic pain.

Carson et al conducted a systematic drug class review evaluating the safety and efficacy of LAOs for the treatment of chronic non-cancer pain.3 The investigators compared the efficacy and harms of LAOs to those of SAOs in treating chronic non-cancer pain. They evaluated 7 randomized controlled trials, focusing on adverse effect profiles, withdrawal rates, and use within specific populations to determine which types of agents should be preferred for the treatment of chronic pain. Unfortunately, because none of the studies incorporated in the review were designed to compare the 2 formulations to each other, no consistent or substantial evidence preferring either type of opioid was found. It also is important to note that all of these studies were listed as “poor quality,” further compounding the issue.

According to the American Pain Society and American Academy of Pain Medicine clinical guidelines for the use of COT in chronic non-cancer pain, there is no evidence to support the belief that LAO treatment is superior to SAO treatment with regard to either safety or efficacy. The guideline states that for initial therapy, SAOs may be preferred to LAOs because of their shorter half-lives and reduced risk for overdose. It further recommends that “opioid selection, initial dosing, and titration should be individualized according to the patient’s health status, previous exposure to opioids, attainment of therapeutic goals, and predicted or observed harms.”4 These recommendations give clinicians a starting point for how to begin addressing patients with chronic pain issues and encourage practitioners to handle chronic pain treatment on a case-by-case basis.

Clinical trials investigating the efficacy of pain treatment usually focus solely on efficacy, without taking into account individual patient factors and overall effects of regimens, formulations, and schedules of agents.5 This explains why no adequate information exists from clinical trials to lead to a substantial conclusion to the proposed question. When considering COT in a patient, an individualized approach that is flexible to the patient’s characteristics may be recommended based on the patient’s specific needs and situation. Factors to consider may include: a comprehensive patient assessment to determine the need for opioid therapy, consideration of pain intensity plus patient-specific characteristics when selecting an opioid, use of a non-invasive routine if possible, consideration of schedule (around-the-clock or as needed), the need for rescue medication, cost and insurance issues, and monitoring to ensure analgesia with the least amount of adverse events.5 Although this does not lead to one formulation being superior to the other, it gives an ideal approach to work with patients to achieve adequate pain control.

The advantages that LAOs are proposed to have over SAOs in the treatment of chronic pain have not been proven in the clinical literature, but, with a systematic, individualized approach, adequate use of either formulation is acceptable to reach analgesia.

Further research specifically addressing this issue is needed, but until that research has been conducted, clinicians should take a comprehensive approach to pain control, considering LAOs and SAOs in light of patient-specific and drug-specific characteristics.


Kelsey L. Bauman, PharmD

Erin M. Timpe Behnen, PharmD, BCPS

Drug Information & Wellness Center

Southern Illinois University Edwardsville

Edwardsville, Illinois

Last updated on: May 8, 2014
First published on: May 1, 2014