"These Pain Meds Aren't Working."

[[{"type":"media","view_mode":"media_crop","fid":"50469","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_9653155982356","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6163","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 225px; width: 300px; float: right;","title":"©Stasique/Shutterstock.com ","typeof":"foaf:Image"}}]]You are the primary care physician for a 63-year-old man who two weeks ago underwent a right total knee replacement (TKR). His orthopedic surgeon prescribed hydrocodone/acetaminophen 5/325, 2 q 6h prn, for his postoperative pain. However, the patient reports that the medication doesn't seem to be relieving the pain very well even though he is taking the maximum daily dose. His surgeon reported that there is no indication of any missed problem that might be causing the pain and told him there wasn't anything else he would prescribe; he noted that when the patient underwent a left TKR four years ago the postoperative pain at that time was well controlled with the same medication.

The patient calls you to ask if you have any suggestions for improving his pain control. Looking through his chart you note that apart from the osteoarthritis that necessitated the TKRs, he is generally in good health. He takes lisinopril 5 mg daily for hypertension, atorvastatin 20 mg daily to control cholesterol, and paroxetine 30 mg daily for depression. He has been taking the first two drugs for approximately 6 years and was started on the paroxetine 4 months ago when he became depressed after losing his job. He reported the depression responded well to the paroxetine and he is seeing his psychiatrist once per month.

1. Based on the patient's history what do you feel is the most likely explanation for the limited analgesia being provided by the hydrocodone/acetaminophen?

A. He is drug seeking and is hoping his physicians will prescribe higher doses of the medication

B. The surgeon has overlooked a problem

C. The limited efficacy of the medication might be a result of a drug-drug interaction

D. None of the above

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Answer: C. The limited efficacy of the medication might be a result of a drug-drug interaction

Hydrocodone is to some degree metabolized to its analgesic metabolite hydromorphone by the hepatic cytochrome P450 2D6 isoenzyme system. Paroxetine, like the other selective serotonin reuptake inhibitor (SSRI) antidepressants, inhibits the cytochrome P450 2D6 system and therefore can prevent the metabolism of hydrocodone limiting its analgesic effects.

2. Which of the following would you recommend?

A. That his psychiatrist discontinue the paroxetine and switch him to a non-SSRI antidepressant

B. Switch him to another opioid

C. Discontinue all opioids as none is likely to be very efficacious for him

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Answer:  B. Switch him to another opioid

As the patient is responding well to the paroxetine and as his pain condition is not a chronic one for which a tricyclic antidepressant or other serotonin-norepinephrine reuptake inhibitor is more likely to provide analgesia than paroxetine, there is no reason to discontinue it. Another opioid analgesic that is not metabolized by the P450 2D6 system may provide more analgesia.

3. Which opioid would you consider switching him to?

A. Immediate-release oxycodone

B. Immediate-release oxymorphone

C. Immediate-release hydromorphone

D. Methadone

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Answer C. Immediate release hydromorphone

Like hydrocodone, oxycodone is also metabolized by the P450 2D6 system and inhibition of this system can reduce analgesic efficacy. Oxymorphone is the analgesic metabolite of oxycodone so that inhibition of the 2D6 system will not affect the analgesia it provides. As the analgesic metabolite of hydrocodone, hydromorphone would also not be affected by the 2D6 system. Thus, either oxymorphone or hydromorphone would likely be effective. However, a reason hydromorphone might be chosen first is that the patient had a past response to hydrocodone and was able to tolerate it without problem indicating that his experience would be similar with hydromorphone.

Although methadone is an effective analgesic because of its pharmacokinetics it usually takes several days to provide maximum analgesia and therefore is not usually indicated for acute pain such as postoperative pain as this patient is suffering.

Source: Smith HS. Opioid metabolism.Mayo Clin Proc. 2009;84:613-624