SAN DIEGO – Pregabalin significantly improved fibromyalgia pain even in patients who were being treated for comorbid depression in a double-blind, crossover clinical trial.
The clinical relevance of this new finding lies in the fact that up to 70% of fibromyalgia patients have a lifetime history of depression, and about 25% are on antidepressant medication when they present for treatment of fibromyalgia. Yet all the studies that led to Food and Drug Administration approval of pregabalin (Lyrica) for treatment of fibromyalgia pain required that participants not be on antidepressant medication. Thus, there has been no information as to the effectiveness and safety of pregabalin in fibromyalgia patients on concomitant antidepressants for comorbid depression, Dr. Lesley M. Arnold explained at the annual meeting of the American College of Rheumatology.
Dr. Lesley Arnold
She presented a 14-week, randomized, double-blind, multicenter study involving 197 patients who met the 1990 American College of Rheumatology criteria for fibromyalgia. All participants also carried a diagnosis of major depression, depression NOS (not otherwise specified), or dysthymia for which they were taking a stable dose of a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).
This was a typical population of fibromyalgia patients: 93% were women, 94% white, with a mean age of 50 years. Their on-treatment depression was mild as evidenced by a baseline mean Hospital Anxiety and Depression Scale–Depression score of 8.0. They were randomized to 6 weeks of placebo or pregabalin started at 150 mg/day dosed twice daily and optimized over the first 3 weeks to either 300 or 450 mg/day as per the product labeling. Three-quarters of patients reached 450 mg/day. After the first 6 weeks of treatment, a 2-week washout period followed, then a switch to the alternate regimen for another 6 weeks.
The primary endpoint was change in mean self-reported pain score based on the average of daily pain scores for the previous 7 days. From a mean baseline pain score of 6.7 on a 0-10 scale, the score dropped to 4.84 on pregabalin, a significantly greater improvement than the 5.45 with placebo. The response to pregabalin was rapid: The improvement in pain scores became significant within the first week and was maintained to the study’s end, reported Dr. Arnold, professor of psychiatry and behavioral neuroscience and director of the Women’s Health Research Program at the University of Cincinnati.
Most patients would find this roughly 28% reduction in pain with pregabalin to be clinically meaningful, she added. In addition, secondary endpoints in the study now being analyzed address improvement in function and global quality of life. Those results will be available within several months.
Pregabalin has a well-established safety profile. No surprises were noted when the drug was used with concomitant antidepressants. The most frequently reported adverse events were dizziness in 28% of patients and sleepiness in 20%. Discontinuation because of adverse events occurred in 6.1% of patients on pregabalin and 3.4% on placebo.
Elsewhere at the ACR meeting, Dr. Arnold presented the results of a phase III, randomized trial in which a novel, investigational, once-daily, controlled-release formulation of pregabalin outperformed placebo in 441 fibromyalgia patients.
Both studies were funded by Pfizer. Dr. Arnold reported receiving research grants from and serving as a consultant to the company.