Chronic pain treatment with opioid analgesics: benefits versus harms of long-term therapy

Abstract

Chronic non-cancer pain (CNCP) is a disabling chronic condition with a high prevalence rate around the world. Opioids are routinely prescribed for treatment of chronic pain (CP). In the past two decades there has been a massive increase in the number of opioid prescriptions, prescribed daily opioid doses and overall opioid availability. Many more patients with CNCP receive high doses of long-acting opioids on a long-term basis. Yet CP and related disability rates remain high, and majority of the patients with CNCP are dissatisfied with their treatments. Intersecting with the upward trajectory in opioid use are the increasing trends in opioid related adverse effects, especially prescription drug abuse, addiction and overdose deaths. This complex situation raises questions on the relevance of opioid therapy in the treatment of CNCP. This article reviews current evidence on opioid effectiveness, the benefits and harms of long-term therapy in CNCP.

Keywords::

• adverse effects
• chronic non-cancer pain
• effectiveness
• function
• hypogonadism
• long term
• mortality
• opioids
• pain relief
• prescription drug abuse

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Opioid analgesics decrease pain in <50% patients with chronic non-cancer pain. Those who respond to opioids, report approximately 30% decrease in pain from baseline.

• • Most studies show small to medium effect size for pain relief in the short term. There is no convincing evidence on long-term efficacy of opioids.

• • Opioids are not superior to NSAID, tricyclic or anticonvulsant drugs in decreasing pain or disability.

• • Opioid analgesic efficacy is not always sustained during continuous and long-term opioid therapy, even in patients with stable disease and despite dose escalation.

• • Evidence for improved physical, emotional or cognitive function with long-term opioid therapy is inconclusive.

• • There may be a greater risk for driving related accidents and psychomotor impairment in patients who have recently begun opioid therapy or who have recently increased their opioid dose.

• • Opioid therapy is associated with high rates of multiple side effects in majority of patients.

• • Treatment with long-acting opioids causes hypogonadotropic hypogonadism in both males and females.

• • A strong association is reported between daily opioid dose and mortality, even at intermediate doses.

• • Methadone causes prolonged QTc interval and torsades de pointes (TdP) in susceptible individuals. The risk of TdP and sudden death increases at a QTc >500 msec.

• • Treatment with high daily doses (>120 mg/day MED), greater day supply of prescription opioids and use of short-acting schedule II drugs increases risk of opioid misuse. Risk factors for abuse are younger age, white males, history of mental health disorder, personal or family history of substance abuse.