Magazine article Clinical Psychiatry News

Overdose Risk Grows with Higher Opioid Doses

Magazine article Clinical Psychiatry News

Overdose Risk Grows with Higher Opioid Doses

Article excerpt


Higher doses of opioids - the equivalent of 50 mg/dL or more of morphine - are more likely than are lower doses to lead to unintentional overdose, according to a report in JAMA.

However, the practice of adding a prescription for as-needed opioids to an existing prescription for regularly scheduled opioids, which allows patients to deal with acute exacerbations of pain, does not raise the risk of unintentional overdose in most patients, as some experts have feared, said Amy S.B. Bohnert, Ph.D., of the Department of Veterans Affairs and the University of Michigan, both in Ann Arbor, and her associates.

Citing a "troubling and dramatic" 124% increase in unintentional deaths from opioid overdose in the United States in recent years, the investigators examined the relationship between opioid-prescribing patterns and opioid-related deaths using a nationally representative sample of 155,434 cases in the VA's National Patient Care Database.

The study subjects included patients taking opioids for cancer pain, chronic bodily pain, headache, neuropathy, and injuries; the prescribed opioid analgesics included codeine, morphine, oxycodone, hydrocodone, oxymorphone, and hydromorphone.

There were 750 deaths attributed to unintentional overdose, for an overall rate of 0.04% among all patients treated with opioids. The risk of overdose increased when the opioid dose was equivalent to 50 mg/dL of morphine, and there was a dose-response relationship in which increasing daily prescribed doses of opioids correlated with increasing risk of overdose death.

As an example, prescribed doses of 100 mg/dL or higher were associated with a hazard ratio of approximately 12.

Dr. Bohnert and her colleagues described their study as the first to assess concurrent prescribing of regularly scheduled opioids plus as-needed opioids. With the exception of cancer patients, participants treated with this strategy showed no excess risk of overdose. "Recent treatment guidelines have indicated that the long-term safety of this strategy for pain exacerbations has not been established, [but] in [this] study we did not find evidence of greater overdose risk associated with this treatment practice, after accounting for maximum daily dose and patient characteristics," they noted (JAMA 2011;305:1315-21).

The researchers also said theirs is the first study of this issue to include patients with cancer. The overall rate of opioid overdose was lower in cancer patients, compared with other subjects, but clinicians should be mindful that renal and liver impairment in this patient group can interfere with the metabolism of opioids and that high doses can place cancer patients at risk. …

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