Turning the Tide on Opioid Prescribing Practices

Patrick I. Borgen, MD, and Kristin Rojas, MD
Published: Sunday, Jan 13, 2019
Patrick I. Borgen, MD

Patrick I. Borgen, MD

In 2017 there was a continued increase in opioid-related deaths in the United States, with more than 60,000 lives lost.1 Most opioid abusers report that their opioids are acquired with their own prescription or a prescription for someone else obtained illegally.2 The majority of the abused opioids are diverted from physician prescriptions, and physicians find themselves at a critical junction that will determine the course of this lethal epidemic.3

In addition to their addictive potential, opioids have untoward effects that are less well known. They impair immune responses, increase angiogenesis, and affect the function of natural killer cells and T cells.4

Opioids may also directly act on tumor cells to encourage growth and metastasis.5 Gupta and her colleagues demonstrated that tumor volume and vascularization of implanted breast cancer were significantly increased in an opioid-treated mouse model, compared with a control cohort treated with naloxone, a mu opioid receptor (MOR) and nonselective receptor antagonist. These effects are thought to be attributable to the direct stimulation of the MOR or its interaction with the VEGF receptor.6,7

The tumorigenic effect of opioids has been further investigated in human studies. A study of a large cohort of 42,151 patients undergoing surgery for colon cancer found that the oncologic outcomes of those who received systemic opioid analgesia were inferior to those of patients who received epidural anesthesia. The nonopioid group had significantly longer overall survival (OS), although the cancer recurrence rates were similar.8 Two recent retrospective studies found that in patients undergoing surgery for early non–small cell lung cancer, perioperative opioid use was associated with decreased OS and increased risk of recurrence.9,10 Pooled data from 2 randomized placebo-controlled trials found that in patients with end-stage cancer and opioid-induced constipation, those treated with methylnaltrexone (MOR antagonist) had a longer median OS, and response to therapy was found to be an independent prognostic factor. Of note, no improvement in OS was observed among the 134 patients with advanced illness treated with methylnaltrexone versus placebo, suggesting that the beneficial effects on surviva are oncology related.11 These lines of evidence in both mouse and human models suggest a correlation between activation of the MOR and worse oncologic outcomes.

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