BY LIZETTE BORRELI
Gabapentin (Neurontin) was found more effective than pregabalin (Lyrica) in reducing leg pain intensity in adults with chronic sciatica and led to fewer and less severe adverse events, according to a randomized, double-blind, double-dummy crossover trial published online on October 15 in JAMA Neurology.
Researchers said the findings suggest gabapentin should be prescribed before pregabalin to permit optimal crossover.
The study — led by Kelvin Robertson, Bpharm, a doctoral candidate in the department of pharmacy, medical services group at Townsville Hospital, and adjunct senior lecturer at the School of Medicine and Dentistry of James Cook University in Australia — is the first prospective randomized cohort of patients with chronic sciatica to compare the head-to-head efficacy of these drugs, the associated frequency and severity of adverse events, and the impact of pregabalin-gabapentin interchange.
These anticonvulsant drugs are both analogs of gamma-aminobutyric acid (GABA), which modulates calcium channel subunits. The researchers hypothesized that they regulate calcium channels in the nerve cells to decrease the contraction of nerves, lessening neuropathic pain.
Gabapentin and pregabalin are both used to treat chronic sciatica, which lasts for at least three months.
To assess the role of gabapentin and pregabalin in treating chronic sciatica, the researchers recruited 18 adults with chronic sciatica attending a specialist neurosurgery clinic in a large tertiary hospital who had not previously received any of these drugs.
Between March 2016 to March 2018, participants were randomized to receive either gabapentin first, then pregabalin, or vice versa. Participants in the gabapentin group started at 400 mg once daily, which was then titrated up to a maximum of 800 mg three times daily; those who took pregabalin started at 150 mg once daily, and then were titrated up to a maximum dosage of 300 mg twice daily. The patients followed the treatment regimen for eight weeks, followed by a one-week washout period in between.
Patients continued to receive their standard neurosurgical care and took concomitant medications, including analgesics if the dose was stable 30 days prior to the start of the study.
Using the mean visual analog scale (VAS), a 10-point scale that rates leg pain from 0 [no pain] to 10 [worst pain], participants reported their leg pain during the last 24 hours. Both drugs led to a significant mean VAS reduction; gabapentin (7.54 to 5.82; p< .001) and pregabalin (7.33 to 6.38; p= .002). However, when unadjusted mean differences in VAS reduction were compared head-to-head, gabapentin proved superior (1.72 vs 0.94; p= .035).
To measure disability, the researchers administered the Oswestry Disability Index (ODI) questionnaire, in which scores range from 0 to 100, with higher scores indicating greater disability. The frequency and severity of adverse events were measured on a 10-point scale, with 10 being the worse possible score.
Both gabapentin and pregabalin led to a significant reduction in disability as measured by the ODI. But the differences in disability between the two drugs were not significant when unadjusted mean differences were compared head-to-head (p= .63).
A total of 38 adverse events were reported in 67 percent of patients: 81 percent for pregabalin compared with 19 percent (p= .002) for gabapentin (p= .002). This was especially true for patients who received pregabalin first.
Gabapentin was associated with less severe adverse events than pregabalin (4.57 vs 6.35; p= .01). Common adverse effects for both drugs dizziness (13 percent), drowsiness (13 percent), and nausea (11 percent).
The researchers concluded that regardless of whether participants received gabapentin first, or last, gabapentin led to a greater mean VAS score and less adverse events.
It remains unknown why one drug led to more side effects compared to the other, especially since they are structurally similar.
The findings warrant further research with a larger sample to decipher why these drugs led to different outcomes.
Study limitations included the small sample size, the effects of treatment duration, and the restricted doses and study time, which may have led researchers to potentially overestimate adverse events with either drug. Other study limitations included the fact that the participants did not receive the maximal dose of gabapentin that can be prescribed, and the maintenance of background therapies may have affected both the efficacy and the development of adverse events.
The study was funded by a grant from the Townsville Hospital Study, Research, and Education Trust.
The researchers reported no conflicts of interest.
LINK UP FOR MORE INFORMATION:
Robertson K, Marshman LAG, Plummer D, et al. Effect of gabapentin vs pregabalin on pain intensity in adults with chronic sciatica: A randomized clinical trial. JAMA Neurol 2018; Epub 2018 Oct 15.