Gabapentin Benefits Few Patients with Chronic Neuropathic Pain

By Will Boggs MD

NEW YORK (Reuters Health) - Fewer than 20% of patients with chronic neuropathic pain experience pain reduction of at least 50% with oral gabapentin treatment, according to a new evidence synopsis.

"There is a solid and consistent evidence base saying that gabapentin at doses of 1,200 mg a day or higher provides good pain relief to some people with moderate or severe neuropathic pain,” Dr. Andrew Moore from the University of Oxford, UK, told Reuters Health by email.

About one in 14 adults experience neuropathic pain (NP), and few patients experience clinically relevant benefit from any intervention (30% to 48% with active treatment versus 11% to 30% with placebo), Dr. Moore and his colleagues note in their February 27 JAMA report

The team evaluated data from 37 randomized clinical trials, involving more than 5,900 patients, in their updated review on the use of gabapentin for neuropathic pain.

Among patients with postherpetic neuralgia (PHN), substantial pain reduction (at least 50%) was achieved in 32% with gabapentin versus 17% with placebo; moderate pain reduction (at least 25%) was achieved in 46% with gabapentin versus 25% with placebo.

Results were similar among patients with painful diabetic neuropathy (PDN): Gabapentin brought substantial relief to 38% of patients versus 21% for placebo, and moderate benefit to 52% of patients versus 37% for placebo.

There were no differences between gabapentin and placebo in trials involving patients with mixed neuropathic pain, spinal cord injury, cancer-related neuropathic pain, phantom pain, radicular leg pain, nerve injury pain, or neuropathies related to HIV.

In a meta-analysis of all trials, gabapentin was associated with modestly, but significantly, higher rates of withdrawal due to adverse events (11% vs. 8% for placebo) - and with slightly, but also significantly, lower rates of withdrawal due to lack of efficacy (2% vs. 3% for placebo).

Adverse-event rates were significantly higher with gabapentin (63%) than with placebo (49%), but rates of serious adverse events were not (3% with both). In particular, gabapentin was associated with more somnolence or drowsiness, dizziness, peripheral edema and gait disturbance or ataxia, compared with placebo.

There is “nothing surprising about the results, as the review updates previous reviews going back 20 years or so,” Dr. Moore said. “What is startling is that despite there being more data and significant improvements in our understanding of sources of bias in trials, the efficacy estimates are almost unchanged.”

“The important issue is the way we now look at outcomes,” he said. “We don’t seek averages, as each patient is an individual, and we now understand that response to therapy is pretty much all or nothing. Patients want high levels of pain relief and adverse events that are tolerable. About 3 in 10 get this outcome with gabapentin in the trials. Of course, 2 in 10 get the outcome with placebo, so the difference is not great, but that is typical for treatments for neuropathic pain.”

“There is reasonable evidence for perhaps four or five drug treatments for neuropathic pain,” Dr. Moore said. “For all other drug treatments, for other interventions, and for non-medical therapies, there is either no good evidence or good evidence that they do not work.”

Dr. Joshua D. Wallach from Yale Law School's Collaboration for Research Integrity and Transparency, in New Haven, Connecticut, who coauthored an accompanying editorial, told Reuters Health by email, “It was interesting to learn that gabapentin is currently the 7th most dispensed prescription in the United States, even though there are only a few indications where a potential beneficial effect has been demonstrated based on evidence summarized in Cochrane reviews.”

“Unfortunately, given the extensive off-label promotion of gabapentin and the fact that hundreds of clinical trials and dozens of Cochrane reviews evaluating both approved and unapproved indications have been performed over the past 25 years, high-quality evidence may not have been efficiently and reliably reported to clinicians,” he said. “The updated review provides a reminder that although gabapentin may have a beneficial effect for certain indications, such as neuropathic pain, there is still limited evidence to support gabapentin’s widespread use for the majority of indications for which it is prescribed.”

Dr. Harsha Shanthanna, a chronic-pain physician from McMaster University, in Hamilton, Canada, told Reuters Health by email, "What is interesting to note is that mixed NP conditions possibly are different than classical NP conditions such as PDN and PHN, where there is clear evidence of peripheral nerve damage. Extending the same thinking, it is not appropriate to expect similar results with gabapentin, for example, in patients with phantom limb pain or cancer-induced pain.”

“Given that no other medications work well for NP, we should go by the suggested recommendations from current practice guidelines,” he said. “However, use gabapentin appropriately and keep in mind the adverse effects.”

SOURCES: https://bit.ly/2FD52Np and https://bit.ly/2FDk3yE

JAMA 2018.

(c) Copyright Thomson Reuters 2018. Click For Restrictions - https://about.reuters.com/fulllegal.asp

For more Pharmacy Learning Network articles, visit the homepage

To learn about Pharmacy Learning Network Live meetings, click here