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Postgrad Med. 2016 Jan;128(1):18-22. doi: 10.1080/00325481.2016.1128306. Epub 2015 Dec 27.

Why oral opioids may not be effective in a subset of chronic pain patients.

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a Research Department , Veract Intractable Pain Clinic , West Covina , CA 91790-3043 , USA.



To identify possible underlying causes of poor oral opioid effectiveness.


Ninety-five (95) adults who were referred for evaluation and medical management of their intractable pain were screened to determine if oral opioids provided enough pain relief to physically and mentally function and carry out activities of daily living. A clinical evaluation included history, physical examination, cytochrome P450 enzyme testing and a hydromorphone injection to help confirm lack of oral opioid effectiveness.


Twenty (20; 21.1%) of the 95 patients reported that three or more oral opioids had not provided enough pain relief to allow them to mentally and physically function and carry out activities of daily living. Patients all reported some typical symptoms of malabsorption including nausea and steatorrhea, and 14 (70.0%) reported that they had observed undigested medication in their stools. Fifteen (15; 75.0%) had experienced pain relief with an injectable opioid. Two major causes for lack of oral opioid effectiveness were apparent: (1) gastrointestinal disorder (11; 55.0%) and (2) cytochrome P450 enzymatic defects (9; 45.0%). In addition to these basic causes, a number of other possible contributing factors were identified which included abdominal, pelvic and spine surgeries, traumatic brain and neck injury, and autoimmune disorders.


There is a group of intractable pain patients who do not effectively metabolize oral opioids. Although gastrointestinal disease and cytochrome P450 enzymatic defects appeared to be dominant causes of oral opioid ineffectiveness, there were other possible contributing factors such as abdominal, pelvic and spine surgeries, head and neck trauma, and autoimmune disease. Pain patients who report poor oral opioid effectiveness should be evaluated for the presence of underlying pathologic conditions which may interfere with oral opioid metabolism and, if found, be considered for nonoral opioid treatment.


Cytochrome P450; Dysautonomia; Gastrointestinal; Ineffective; Malabsorption; Opioid; Oral

[Indexed for MEDLINE]

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