Gabapentin Plus Opioids for Chronic Pain?

DENVER — Combining gabapentin (Neurontin) with opioids showed no advantage over opioids alone for chronic pain patients, a small preliminary study presented here showed.

Patients who had either treatment plan experienced statistically significant improvement in pain over baseline, but adding gabapentin to opioids was not superior in providing pain relief, reported N. Nick Knezevic, MD, PhD, of the University of Illinois in Chicago, and colleagues, at the American Academy of Pain Medicine meeting.

"We have had a huge increase in the number of gabapentin prescriptions over the past 10 years, including among primary care physicians," Knezevic said.

"In these days, when we are focusing on reduction of opioids due to opioid crisis in the U.S., gabapentin could be an important part of multimodal non-opioid pain management," he told MedPage Today. "However, it should not be given to all patients since the effectiveness in chronic pain patients, particularly in those with low back pain, is limited ."

In the U.S., gabapentin and pregabalin (Lyrica), two clinically-used medications in the gabapentinoid drug class, have tripled in use from 2002 to 2015. Both drugs have been approved by the FDA for treatment of partial seizures and postherpetic neuralgia , and both frequently are used for off-label indications .

Prescriptions for anticonvulsant drugs like gabapentin and pregabalin have soared for several reasons, noted Oliver Enke, MBBS, MD, of the University of Sydney, who was not involved with the study. The drugs have shown to be effective for neuropathic pain conditions, and "in the absence of effective guidelines, prescribers may also seek an alternative to stronger analgesics such as opioids," Enke told MedPage Today.

"The fact that anticonvulsants are often advertised to be effective for ‘nerve pain’ may mislead the prescriber to assume efficacy for low back pain or sciatica," he added.

Recent research has shown that combining gabapentin with opioids may have a potentially life-threatening interaction : in a matched case-control study, concomitant gabapentin and opioid exposure was associated with a 49% higher risk of dying from an opioid overdose. The abuse potential of gabapentin also has created concerns about increased risks of respiratory depression and death when used with opioids or other central nervous system depressants.

In this retrospective study, Knezevic and colleagues looked 156 chronic pain patients who were treated at a single medical center. In this sample, 78 patients had used gabapentin in combination with opioids and 78 propensity-matched controls had used opioids only.

The main cause of pain was chronic low back pain (61%), and the average age of patients was about 60. Follow-up took place over an average duration of about 30 months. Mean morphine milligram equivalent (MME) units was 59.22 (median MME was 45).

All patients experienced significant pain improvement (-3.36) in the Numeric Rating Scale (NRS; a scale of 0 to 10, where 0 is no pain and 10 is the worst possible pain), compared with their baseline ( P <0.01).

Among patients taking a combination of gabapentin (mean dose 1,451 mg) and opioids, the average NRS reduction was -2.81; among patients taking opioids alone, it was -3.91 ( P <0.01). Patients taking the combination treatment moved from 7.9 to 5.1 on the pain scale; patients taking opioids alone went from 8.3 to 4.4.

One reason for this finding might be the high prevalence of low back pain in this study, noted Knezevic: a systematic review led by Enke last year found moderate- to high-quality evidence that anticonvulsants like gabapentin and pregabalin were ineffective for treating low back pain or lumbar radicular pain.

Overall, the results are in line with recent guidelines , which do not recommend the use of gabapentinoids for low back pain, Knezevic added.

This analysis is limited by its preliminary, observational nature and its small sample size. Unknown confounders may have influenced results.

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