The day has come when patients with chronic pain who require higher levels of opioids to manage their condition can first be evaluated with laboratory tests to guide clinicians in their next treatment recommendations.

Forest Tennant, MD, DrPh, of Intractable Pain Management in California, told an audience at a session this week, “when a patient is going into dosages above the standard, that patient needs to be underpinned with a series of laboratory tests.”

Discussing pharmacogenetic testing for patients in chronic pain, Dr. Tennant first mentioned CYP450 screening.  “Looking for CYP450 abnormalities can be very helpful, because if patients have  these abnormalities, they don’t metabolize these drugs,” he said. These patients will require opioids that bypass the CYP450 system, including medications like morphine, hydromorphone, tapentadol, and levorphanol.

Dr. Tennant also recommended screening for opioid receptor mu-1 binding, since those patients who have a low binding effect are likely going to need higher dosages of opioids.

Discussing catechol-o-methytransferase , Dr. Tennant said this genetic test measures how the brain reacts to opioids. “If the catecholamine-degrading enzyme is too active and breaks down the catecholamine, you are going to need more opioids,” Dr. Tennant noted. This is often true in those patients with centralized pain, Dr. Tennant said, because these patients typically require multiple treatment agents.

“When polypharmacy is involved, these patients have to be monitored closely with screening, their families have to be involved, and other practitioners need to be involved, as well,” Dr. Tennant explained.

It is also important to consider the possibility of opioid malabsorption and hormone issues in those patients who are not responding to treatment, Dr. Tennant advised.

Documenting all of these tests is critical, Dr. Tennant explained, not only because it protects the clinician legally, in that it shows they are employing best practices, but more importantly it may help a clinician determine why a particular treatment regimen may be unsuccessful.

In addition to genetic tests, Dr. Tennant advised that a basic workup for patients with pain should include determining if that patient has centralized pain, as well as performing a laboratory workup on the patient’s current opioid levels and hormone profiles.

Dr. Tennant said that clinicians can easily identify patients with centralized pain by asking one question: “Does your pain come and go, or do you have it all the time?” He further explained, “If they are in constant pain, they have centralized pain.”  Patients with centralized pain often require multiple pharmacologic agents, including antidepressants, anti-inflammatory drugs, opioids, stimulants, and glial cell modulators, such as antivirus, minocycline, ketamine, and naltrexone.

Serum opioid levels are “very accessible for all patients, and they are important to obtain when you go into nonstandard opioid ranges. You want it on the chart because you want to know if they are taking the drug, and can they tolerate the regimen you are considering,” Dr. Tennant remarked.

Clinicians should also make sure that the patient has “gone through the steps” of the World Health Organization analgesic ladder, Dr. Tennant  cautioned.  Step 1 includes non-opioid analgesics and adjuvant therapy; step 2 includes adding a weak opioid, and step 3 includes stepping the patient up to more potent opioid analgesics, as well as using non-opioid analgesics and adjuvant therapy.

Dr. Tennant cited data demonstrating that the number one major unmet need in pain management in the United States is failure from standard treatment.1

“There’s this myth that everyone can get by on 50 mg of morphine, but that’s just not true. There’s a lot of people who have very serious problems that require higher doses and need help,” he concluded.


1. DeBattista C, Eisendrath SS, Lichtmacher JE. Chronic pain disorders. In: Papadakis MA, McPhee SJ, Rabow MW, eds. Current Medical Diagnosis and Treatment 2015. 14th ed, New York, NY: McGraw Hill Lange; 2015:1037-1039.