The original case for using long-term opioid therapy to treat chronic noncancer pain was based on safety assumptions that subsequent experience calls into question. In 1996, the American Pain Society and the American Academy of Pain Medicine issued a consensus statement supporting long-term opioid therapy (7
). This statement acknowledged the dangers of imprudent opioid prescribing but concluded that the risk for de novo addiction was low; respiratory depression induced by opioids was short-lived, occurred mainly in opioid-naive patients, and was antagonized by pain; tolerance was not a common problem; and efforts to control diversion should not constrain opioid prescribing. Unfortunately, experience regarding the risks for opioid addiction, misuse, and overdose in community practice has failed to confirm these assertions (2
Consistent estimates of the prevalence of prescription opioid abuse among primary care patients receiving long-term opioid therapy remain elusive. The few surveys in community practice estimate rates of prescription opioid abuse from 4% to 26% (4
), but recent studies suggest that potentially serious opioid misuse is not rare (8
). For example, Fleming and colleagues conducted 2-hour interviews with 801 patients receiving long-term opioid therapy who were being treated by 235 Wisconsin physicians (8
). They found rates of 26% for purposeful oversedation, 39% for increasing dose without prescription, 8% for obtaining extra opioids from other doctors, 18% for use for purposes other than pain, 20% for drinking alcohol to relieve pain, and 12% for hoarding pain medications.
Widespread opioid prescribing for chronic pain leads to greater opioid availability in homes and communities, with public health consequences. According to the Centers for Disease Control and Prevention, fatal overdoses involving opioid analgesics have increased sharply over the past decade (12
). Currently, more than 13 000 deaths from overdose per year involve prescription opioids, and deaths from drug overdose have surpassed motor vehicle accidents as the leading cause of injury death for persons 35 to 54 years of age (13
). The risk for opioid overdose increases markedly with dose among patients receiving long-term opioid therapy (14
). Use of diverted prescription opioids by adolescents is now among the most common forms of drug abuse (17
). Because diversion can result in addiction or fatal overdose, decisions about prescribing need to take the risks to family and community into account in addition to the direct risks to patients.
Direct risks of long-term opioid therapy are not limited to opioid addiction and overdose. Potential medical risks include serious fractures, breathing problems during sleep, hyperalgesia, immunosuppression, chronic constipation, bowel obstruction, myocardial infarction, and tooth decay secondary to xerostomia. Clinical data suggest that neuroendocrine dysfunction may be common in both men and women, potentially causing hypogonadism, erectile dysfunction, infertility, decreased libido, osteoporosis, and depression (18
). Recent studies linked higher opioid dose to increased opioid-related mortality (15
). Controlled observational studies reported that long-term opioid therapy may be associated with increased risk for cardiovascular events (19
). A descriptive study of 133 persons aged 65 years or older receiving long-term opioid therapy found that 5% were hospitalized for opioid-related adverse events (21
). Nonetheless, recent guidelines from the American Geriatrics Society concluded that all patients with moderate to severe pain be considered for opioid therapy (22
). This recommendation was based in part on the unfavorable safety profile of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for managing chronic pain in older adults. However, a subsequent meta-analysis concluded that the safety of long-term opioid therapy in elderly patients is not yet established (5
). We conclude that medical risks of long-term opioid therapy have not been adequately studied, although recent research identifies important risks associated with opioid dose. Additional evidence is needed to determine the net benefit of long-term opioid therapy by dose, weighing its benefits against the full spectrum of possible adverse effects.