Patients with fibromyalgia have access to a limited number of therapeutic options. One of 3 drugs approved for patients with fibromyalgia, pregabalin is an anticonvulsant and α-2-Δ subunit receptor ligand that has shown clinically meaningful benefits across multiple fibromyalgia symptom domains.
“Pregabalin therapy in patients with fibromyalgia is modestly effective in terms of response, but a good number of patients are able to achieve meaningful benefit in terms of pain control, improvement of sleep, functioning, and quality of life,” Santosh Bhusal, MD, Division of Rheumatology, Metrohealth Medical Center, Cleveland, OH, and colleagues explained. “Pregabalin is cost saving to the society, especially if used at dosages ≥450 mg [a] day.”
Seeking to highlight the clinical utility of pregabalin in the management of fibromyalgia, the study authors conducted a review on the efficacy, safety, and cost-effectiveness of the drug.
Effects of Pregabalin on Pain, Sleep, and Quality of Life
As part of their review, the study authors discuss the mechanism of action of the drug as well as its pharmacokinetics. Taking a closer look at the clinical utility of pregabalin, they note that the drug does not only show benefits in pain management, but can also be used for sleep and quality of life.
Numerous randomized trials, including 2 meta-analyses, demonstrate the efficacy of pregabalin in the treatment of fibromyalgia pain, and were studied by the authors for the purpose of this review. Of note, one double-blind trial of 529 patients randomized to receive 150 mg, 300 mg, or 450 mg of pregabalin or placebo for 8 weeks resulted in significant pain improvement in patients receiving pregabalin 450 mg, compared with control. This improvement in pain was based on reduction of end point mean pain scores on weeks 1 to 7, and reports of >50% pain improvement from baseline (28.9% pregabalin vs 13.2% placebo; P = .003).
With regard to treatment of sleep disturbance, the authors were intrigued by pregabalin’s enhancement of slow-wave sleep. In a double-blind study of 12 healthy volunteers, patients treated with pregabalin 450 mg daily had higher proportions of stage 3 and 4 delta wave sleep compared with counterparts taking alprazolam and placebo. Pregabalin use was also linked to fewer awakenings of longer than a 1-minute duration. Another analysis of 2 randomized trials demonstrated that patients with fibromyalgia taking pregabalin had statistically significant improvements in sleep quality diary and medical outcome sleep study, with the difference with placebo going beyond the thresholds for clinical meaningfulness; results were reportedly more consistent at doses ≥450 mg a day.
Significant improvements have been noted in results of the fibromyalgia impact questionnaire (FIQ) with pregabalin doses of 450 mg and 600 mg daily, compared with placebo in a randomized trial. Another study evaluating pregabalin 450 mg daily also demonstrated noteworthy improvement in FIQ results compared with placebo. Dr Bhusal and colleagues noted that studies surrounding the SF-36 health survey—the other most commonly used measure for function and quality of life other than FIQ—yielded diverse results that were inconsistent across different studies.
Safety and Accessibility of Pregabalin
When looking at data evaluating the safety and accessibility of pregabalin, Dr Bhusal and colleagues observed that the rate of discontinuation for pregabalin is low, and although side effects are common with the drug, they do not interfere with functions of daily life.
According to the authors, randomized trials have indicated that approximately 80% to 90% of patients taking pregabalin had treatment-emergent adverse events, compared with approximately 70% to 75% of patients taking placebo. Dizziness and somnolence were the most common side effects reported.
Although weight gain is a less common side effect, it has been shown to lead drug discontinuation. In fact, Dr Bhusal and colleagues state that the incidence of weight gain has been shown to be as high as 18% to 26% annually in some long-term studies.
Other than these side effects, rare adverse events that have led to discontinuation of pregabalin therapy include chest pain, abnormal liver function tests, and suicidal ideation. Causal association of these events is hard to determine, they noted however, because they occur only once or twice per randomized trial and were not linked to pregabalin use.
Based on the information in pharmacoeconomic studies, the authors assert that pregabalin is cost-effective. According to a Markov model assessing cost-effectiveness of pregabalin in the United States, total and indirect costs for patients taking the drug at 300-mg and 450-mg doses daily were lower compared with placebo at 12 weeks; outpatient visit and medication costs, however, were slightly higher, Dr Bhusal and colleagues noted. Both dosages elicited more total, direct, and indirect cost-savings than placebo at 1 year. Pregabalin was also found to be more cost-effective than duloxetine, gabapentin, and milnacipran. Long-term pregabalin use in patients with fibromyalgia—especially at doses ≥450 mg a day—is cost-effective and comparable to other drugs used in this patient population, the study authors suggested.
“Until the availability of better drugs in the future, pregabalin is well suited to serve as one of the ‘anchor drugs’ in fibromyalgia,” Dr Bhusal and colleagues concluded.
- Bhusal S, Diomampo S, Magrey MN. Clinical utility, safety, and efficacy of pregabalin in the treatment of fibromyalgia. Drug Healthc Patient Saf. 2016;8:13-23.