Tuesday, September 22, 2009

Ultra-High Opioids: When “Too Much” is Just Right

Controversy still exists about the long-term prescribing of opioids for chronic noncancer pain (CNCP) conditions, and particularly regarding the safety and effectiveness of higher opioid doses. Yet, there appears to be a subset of patients with CNCP who require and thrive on ultra-high doses exceeding morphine-equivalent opioid doses of 1,000 mg/day — demonstrating that what some practitioners might consider as being way too much opioid is just the right amount for certain patients. However, careful patient management is necessary according to a recent journal article.

Writing in the September 2009 issue of the journal, Practical Pain Management, Jennifer Schneider, MD, and colleagues note that patients requiring high doses of opioids are usually quite ill and impaired due to their chronic pain, often bed-ridden or house-bound, and withdrawn from socialization for a considerable period of time [see reference below for article access]. While some observers and published guidelines have claimed that morphine-equivalent opioid doses greater than 200 mg/day are ineffective, there is no evidence from good-quality clinical trials to support such claims. Schneider et al. emphasize that there is no maximum safe dose of opioids and there are wide variations — as much as a 40-fold variation — in the dose required to achieve patient comfort and function without causing sedation or physical impairment.

The authors propose classifying morphine-equivalent doses of 200 mg/day or less as “low or standard dose,” 201 to 1,000 mg/day as “high dose,” and greater than 1,000 mg/day as “ultra-high dose.” Often, multiple opioid formulations are required at the ultra-high level, including (a) daily regimens of sustained-release or long-acting opioids to help control baseline pain, (b) short-acting or immediate release opioids taken “as needed” for flares or episodes of breakthrough pain, and (c) for breakthrough pain that quickly reaches maximum intensity, a rapid-acting opioid (eg, fentanyl lozenge or sublingual oxycodone) may be needed briefly. Morphine-equivalents of all opioids taken each day are combined to calculate the total dosage.

The authors do concede that patients taking ultra-high doses require extra care, and extra time by practitioners, and they recommend a number of important management strategies (see Table 3 at right from the article). As one strategy, urine drug testing (UDT) is recommended; however, they caution that practitioners must understand the limitations of UDT and potentials for misleading results. Furthermore, quantitative analyses of drugs in urine cannot be used to assess therapeutic compliance, since such measures vary depending on individual metabolism and when the opioid was taken in relation to when urine was collected.

It is essential to establish with patients, and their families, realistic goals and objectives of opioid therapy. These might include 30% to 50% pain relief, elimination of bed- or house-bound days, cessation of emergency room visits, or a resumption of favorite activities and social interactions. Improved functionality is as important a goal as pain relief. However, the authors note, “…there is no necessity to ever lower or cease opioid treatment if the patient’s pain and function are significantly improved and the patient is tolerating the medication well.” Many patients reach a plateau dosage after titration and remain at a relatively constant dose range, albeit ultra-high, for years. “It is a myth that tolerance to the pain-relieving effect of opioids is to be expected,” they write. Increased pain after months or years is more likely due to progression of disease rather than late-developing opioid tolerance.

Commentary: While Schneider and coauthors recommend involving the patient’s family, if possible, one area not discussed is counseling patients and their caregivers on handling opioid emergencies; that is, recognizing overmedication and overdose, and what to do if these occur. This could be especially critical when high doses of opioids, or dose increases, are prescribed and before opioid tolerance has developed. Also, at any time there could be metabolic interactions with newly prescribed drugs causing an unexpected increase in opioid serum levels (with the exception of morphine, hydromorphone, and oxymorphone, opioid analgesics are metabolized via the same CYP-450 liver enzymes as many other drugs). And, when a patient is allowed “as needed” opioids for flares or breakthrough pain there could be periods of some overmedication depending on frequency of administration or how the patient metabolizes the analgesic. Practitioners may feel more comfortable in prescribing higher opioid doses if they know patients and caregivers are educated on appropriate safety procedures in the event of unanticipated overmedication or accidental overdose.

Reference: Schneider J, Anderson A, Tennant F. Patients who require ultra-high opioid doses. PPM. 2009(Sep);9(7):10+. A free copy of this article is available to Pain-Topics readers [click here], courtesy of Practical Pain Management. For more information on this journal [click here].