New research shows that the anticonvulsant drug pregabalin (Lyrica, Pfizer) provides rapid and sustained relief from pain and pain-related sleep disturbance in patients with spinal cord injuries (SCIs).
The study is exciting because the results lay important groundwork to fill a treatment gap for SCI patients, according to investigators Luis Sanin, MD, Clinical Sciences, Medicines Development Group and Bruce Parsons, MD, PhD, senior medical director, US Medical Affairs, Primary Care Business Unit, both at Pfizer Inc.
"As the neuropathic pain associated with spinal cord injury is difficult to treat, we believe that pregabalin is an important treatment option for these patients" said Dr. Parsons.
The study, funded by Pfizer, was presented here during the American Academy of Neurology's 64th Annual Meeting.
Cause of Injury
Chronic pain occurs in about two-thirds of patients who suffer a spinal cord injury. Central neuropathic pain occurs in an estimated 40% of SCI patients.
Pregabalin is a 3-substituted analogue of gaba-amino butyric acid (GABA) and a compound related to gabapentin (Neurontin). In animal models of neuropathic pain, damaged neurons can become hyperexcitable. "In these models, pregabalin can help damaged neurons which are firing abnormally fast to fire more normally, and restore a more normal pattern of neuronal activity," said Dr. Parsons.
Pregabalin is already approved in the United States for the management of fibromyalgia, neuropathic pain associated with diabetic peripheral neuropathy, and for postherpetic neuralgia. It is also approved for adjunctive therapy for adult patients with partial-onset seizures.
Patients included in the current trial were adults who had a complete or incomplete lesion at levels C2-T12. Most of the injuries were the result of trauma, including accidents, gun shot wounds, and falls. Also included were patients who had spinal cord injuries related to ischemia or removal of a benign spinal cord tumor. Most patients had lived with their spinal cord injury for several years — some for more than a decade.
In addition to having an SCI, trial participants were required to have below-level central neuropathic pain that was continuous for at least 3 months or remitting/relapsing for at least 6 months.
"This type of neuropathic pain, which is two levels (dermatomes) below the level of injury, is often considered to be the most difficult neuropathic pain to treat in this population," said Dr. Parsons. Patients in the study had an average pain score of 6.6 on a 10-point scale.
The patients were randomly assigned to receive placebo (n = 108) or pregabalin (n = 111). The total daily dose of pregabalin was 150 to 600 mg given daily in 2 divided doses. The double-blind study continued for 16 weeks: 4 weeks of titration, followed by a 12-week maintenance phase.
During the trial, study patients could continue receiving their other medications, such as baclofen or benzodiazepines. They were also permitted to receive acetaminophen as a rescue medication for pain, up to 4 g daily.
Not allowing patients to continue receiving these other medications wouldn't have been feasible, said Dr. Parsons. "Patients with spinal cord injury often have different types of pain, including musculoskeletal and visceral, pain from spasticity, in addition to neuropathic pain, and it's important to allow them to continue their medications."
The study met the primary endpoint of change in mean Duration Adjusted Average Change (DAAC) in pain, a weighted average of change from baseline in mean pain scores based on treatment duration. Pregabalin was associated with a significant improvement in the DAAC, with difference from placebo of -0.59 (P = .003).
Secondary analyses were also statistically significant, including the proportion of pregabalin patients achieving a 30% or greater and a 50% or greater reduction from baseline to endpoint in mean pain scores, compared with placebo. As well, patients receiving pregabalin had a significant reduction in pain-related sleep interference scores compared with those receiving placebo (P ≤ .001).
The most common adverse events were somnolence and dizziness, which were more common in patients taking pregabalin.
"The rates of somnolence in both the pregabalin and the placebo arms were higher in this trial than in pregabalin studies in other neuropathic pain conditions, such as painful diabetic neuropathy," said Dr. Parsons. "This can be explained, at least in part, by the fact that the SCI patients were allowed to remain on other medications that also can cause somnolence, such as the benzodiazepines."
However, he added, somnolence and dizziness associated with pregabalin often improve during the first several weeks of treatment.
The current trial is one of two independent studies to date using pregabalin in patients with SCI. An earlier trial was carried out several years ago in Australia, whereas the current trial was conducted in ten countries, including sites in the United States, Latin America, Russia, and Japan.
"With the addition of this study, pregabalin is now the most extensively studied medication in SCI patients with neuropathic pain," said Dr. Parsons. Other drugs that have been studied also had positive findings but those studies had far fewer patients, often no more than 40, he said.
Approached for comment, Hui-Lin Pan, MD, PhD, Helen T. Hawkins Distinguished Professor, and deputy division head for research, Division of Anesthesiology and Critical Care, the University of Texas MD Anderson Cancer Center, Houston, agreed that effective treatment of central neuropathic pain remains a major therapeutic challenge.
"This randomized clinical study provides additional evidence showing the beneficial effect of pregabalin for patients with central neuropathic pain," Dr. Pan toldMedscape Medical News.
"Further studies are still needed to determine if the effect of pregabalin is significantly better than other treatments such as antidepressants, anticonvulsants and opioids."
The study was supported by Pfizer. Dr. Parsons is employed by Pfizer.
American Academy of Neurology 64th Annual Meeting. Emerging Science Poster #005. Presented April 25, 2012.
Pauline Anderson • Medscape Medical News © 2012 WebMD, LLC