Chronic Low Back Pain: Pregabalin Helps Reduce Pain and Sleep Interference

A new study suggests that pregabalin shows significantly greater improvements in pain-related interference of sleep relative to usual care in patients with chronic low back pain with accompanying neuropathic pain (CLBP-NeP).

Sleep disturbance is particularly important for CLBP-NeP patients. Earlier studies have shown that patients reported significantly greater sleep disturbance and impairment of quality of life at higher pain severity levels. In Japan, nearly 30% of patients with CLBP have a NeP component. Sleep disturbance is one of the most prevalent coexisting conditions in patients with CLBP-NeP. This presents a significant challenge for treatment, because many standard analgesics — including acetaminophen and NSAIDS – have generally poor efficacy for NeP.

Pregabalin, manufactured by Pfizer under the brand name Lyrica and by Beximco Pharma under the brand name Nervalin, is considered first-line treatment for the treatment of pain associated with diabetic neuropathy, post-herpetic neuralgia, and central neuropathic pain. However, its use for acute pain, post-surgical chronic pain, and other potential conditions is controversial at best. The Japanese study, published in the Journal of Pain Research, was sponsored by Pfizer.

The study authors noted that, “Observational studies from routine clinical practice in primary care settings in Germany and Spain in which analgesic therapy was based on the clinical judgment of the treating physician have also shown that pregabalin improves pain and sleep disturbance when used for the treatment of CLBP with an NeP component.”

The prospective, non—interventional, observational study lasted eight weeks and enrolled Japanese adults (≥18 years) with CLBP–NeP of duration ≥three months and severity ≥five on a numerical rating scale (0= no pain, 10= worst possible pain). Pregabalin was given for eight weeks to 157 patients, whereas 174 patients were given usual care. The primary endpoint was efficacy outcome was change from baseline to eight weeks in pain–related interference with sleep, assessed using the Pain–Related Sleep Interference Scale (PRSIS; 0= did not interfere with sleep, 10= completely interferes with sleep). Quality of life, measured by the Roland-Morris Disability Questionnaire, was among the secondary endpoints.

All patients used a variety of medications for pain. NSAIDS were the most commonly reported analgesics, used by 96.8% and 95.4% of pregabalin and usual care patients, respectively, and there was polypharmacy in both treatment arms. No patients were enrolled who had been treated with pregabalin during the three months prior to the study. Pregabalin dosing was flexible, and the range of doses among these patients was 25 mg/day to 300 mg/day.

For the primary endpoint, pregabalin resulted in significantly greater improvements in PRSIS at week eight and at week four. Relative to usual care at week eight, pregabalin improved pain and function (both P<0.001), and showed global improvements since beginning study medication (P<0.001).

“The significant improvements in sleep and pain are not surprising given the reciprocal relationship between these two outcomes such that not only does pain interfere with sleep but poor sleep increases pain sensitivity,” the study authors continued. “Additionally, it has been suggested that improvements in function and health state in patients treated with pregabalin are not exclusively mediated through analgesic efficacy, but rather result from combined effects on pain and sleep interference. “

There were no serious adverse events (AEs), and less than 10% of patients discontinued the study due to treatment-related AEs. Study limitations include that the study was observational and open-label as well as non-randomized, since choice of treatment was based on the clini&shy;cal judgment of the treating physician.

“This design may also be considered as setting an imbalance in clinical equipoise, since the known effects of pregabalin on the part of the clini&shy;cians may have biased patient selection, subsequently result&shy;ing in the significantly greater pain observed in this group,” the authors noted. “Nevertheless, this design can also be considered as a strength of the study, since it allows a physician to assess a drug’s efficacy and safety in real-world clinical practice, which does not itself endorse balanced treatment strategies.”