Pregabalin Significantly Improves Fibromyalgia Pain in Patients Who Also Suffer From Depression

Newswise — SAN DIEGO – Pregabalin (Lyrica® Capsules CV) can significantly improve fibromyalgia pain in people who also are being treated for depression, according to research presented this week at the American College of Rheumatology Annual Meeting in San Diego.

Fibromyalgia is a common health problem that causes widespread pain and tenderness (sensitive to touch). The pain and tenderness tend to come and go, and move about the body. Most often, people with this chronic (long-term) illness are fatigued (very tired) and have sleep problems. And, the disease has been linked with mood disorders, such as depression. In fact, 50 to 70 percent of people with fibromyalgia report a lifetime history of depression, and approximately 25 percent have a history of taking antidepressants.

Pregabalin is approved for the treatment of fibromyalgia in the United States, Japan, and other countries. But, because prior pregabalin/fibromyalgia studies excluded the use of antidepressants in treatment, information about the effectiveness and safety of pregabalin for the treatment of pain in people with fibromyalgia who are being treated with antidepressants for their depression is lacking.

“Depression is common in patients with fibromyalgia,” explains Lesley M. Arnold, MD; professor of psychiatry and behavioral neuroscience; University of Cincinnati College of Medicine, Cincinnati, Ohio; and lead investigator in the study. “Many patients present to their doctor for treatment of fibromyalgia pain already taking antidepressants for their depression. This is the first study to evaluate the efficacy and safety of pregabalin for treatment of fibromyalgia pain in patients who are also taking antidepressants for depression.”

With this in mind, researchers completed a study to determine if pregabalin would affect pain levels in people with fibromyalgia who were also being treated for depression. The study included 197 patients who were, on average, 50 years of age and overwhelmingly white females. To join the study, patients had to meet the 1990 American College of Rheumatology Criteria for Fibromyalgia (including manual tender point exam), have an average pain level of at least four out of 10 on the Numeric Rating Scale, (0 = no pain and 10 = worst possible pain), have a documented diagnosis of depression and be taking stable dose of an antidepressant medication — either a selective serotonin reuptake inhibitor (such as Celexa®, Lexapro®, Prozac®, Paxil® or Zoloft®) or a serotonin-norepinephrine reuptake inhibitor (such as Cymbalta®, Effexor®, or Pristiq®). The antidepressant treatment was continued throughout the study.

Patients were on study treatment for a total of 14 weeks. There were two six-week treatment periods when patients received either pregabalin or placebo, with a two-week break in between these periods. Each patient was randomly assigned to receive either pregabalin in the first six weeks, then placebo in the last six weeks, or to receive placebo first, then pregabalin. None of the patients knew which treatment they were receiving at any point in the study. Pregabalin was started at a dose of 150mg per day and within three weeks was increased to 300-450mg per day based on patient response; this dose was continued for the rest of the treatment period.

During the study, 193 patients received at least one dose of study medication; 181 patients received at least one dose of pregabalin, and 177 received at least one dose of placebo. At the beginning of the study, the average pain score amongst participants was 6.7. The average pain score dropped to 4.84 after treatment with pregabalin and to 5.45 after treatment with placebo. Pregabalin treatment significantly improved patients’ pain compared to placebo.

Side effects were reported in 77.3 percent of those on pregabalin and 59.9 percent of those on placebo. For pregabalin treatment the most common events were dizziness (28.2 percent) and drowsiness (19.9 percent). A total of four serious adverse events were reported, three of which occurred in those on pregabalin and one on placebo; the researchers concluded these events were not related to the treatment. Of those taking pregabalin, 6.1 percent did not complete the study due to a side effect, compared with 3.4 percent of those taking placebo.

“The results of this study demonstrate that pregabalin is safe and effective in reducing fibromyalgia pain in patients who are also taking an antidepressant to treat their depression,” says Dr. Arnold.

The American College of Rheumatology is an international professional medical society that represents more than 9,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. For more information about the meeting, visit http://www.acrannualmeeting.org/ or join the conversation on Twitter by using the official hashtag: #ACR13.

Editor’s Notes: Dr. Arnold will present this research during the ACR Annual Meeting at the San Diego Convention Center at 2:30 PM in Room 6A on Tuesday October 29. Dr. Arnold will be available for media questions and briefing at 1:30 PM Tuesday, October 29 in the on-site press conference room, 27 AB.

L6

Efficacy and Safety of Pregabalin in Patients with Fibromyalgia and Co-Morbid Depression Receiving Concurrent Antidepressant Therapy: A Randomized, 2-Way Crossover, Double-Blind, Placebo-Controlled Study

Lesley M. Arnold1, Piercarlo Sarzi-Puttini2, Pierre Arsenault3, Tahira Khan4, Pritha Bhadra Brown5, Andrew Clair5, Joseph Driscoll4, Jaren Landen4 and Lynne Pauer4, 1University of Cincinnati College of Medicine, Cincinnati, OH, 2Azienda Ospedaliera Polo Universitario L. Sacco, Milano, Italy, 3Université de Sherbrooke, Sherbrooke, QC, 4Pfizer Inc, Groton, CT, 5Pfizer Inc, New York, NY

Background/Purpose: Fibromyalgia (FM) is characterized by chronic widespread pain and often associated with mood disorders including depression. Approximately 50–70% of FM patients have a lifetime history of co-morbid depression and ~25% have a history of antidepressant therapy. Pregabalin (PGB) is approved for the treatment of FM in the US, Japan and other countries. Because prior PGB FM clinical trials excluded the concomitant use of antidepressant medications, information about the efficacy and safety of adding PGB to antidepressant medications in patients with depression and FM is lacking.

Methods: This was a randomized, 2-way crossover, double-blind, placebo-controlled study of PGB in FM subjects with co-morbid depression receiving concurrent antidepressant medication for the treatment of depression with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI). Patients were aged ≥18 years, met the 1990 American College of Rheumatology criteria for FM, had a mean numeric rating scale (NRS) pain score of ≥4 (NRS scored from 0–10), a documented diagnosis of depression, and were being treated with a stable dose of a single SSRI or SNRI for the 2 months prior to randomization. All patients were randomized 1:1 to placebo or PGB (optimized to 300 or 450 mg/d) for the first 6-week treatment period (3 weeks dose optimization, 3 weeks fixed dose for each treatment period), and then switched to the alternate regimen for the second 6-week treatment period. Treatment periods were separated by a 2-week, single-blind taper/placebo washout. Stable antidepressant medication was continued throughout the study. The primary efficacy endpoint was mean pain score based on the mean of the last 7 daily pain scores.

Results: A total of 197 patients (93% female, 94% white, mean age 50 years) were randomized to treatment; 181 received ≥1 dose of treatment with PGB and 177 placebo. The mean time since diagnosis of depression was 12.3 years and the baseline mean Hospital Anxiety and Depression Scale – Depression score was 8.0, reflecting mild depression. At baseline, 52.3% were taking an SSRI, 47.7% an SNRI, and the mean pain score was 6.7. At the end of treatment, the least squares (LS) mean (SE) pain score was significantly lower with PGB (4.84 [0.15]) than with placebo (5.45 [0.16]) (LS mean difference -0.61; 95% confidence interval -0.91 to -0.31; p=0.0001). Treatment emergent adverse events (AEs) were reported in 77.3% and 59.9% of patients receiving PGB and placebo, respectively. The most frequently reported AEs with PGB were dizziness (28.2%) and somnolence (19.9%). A total of 4 serious AEs were reported (3 with PGB and 1 with placebo), none of which were considered related to treatment. In patients receiving PGB, 6.1% discontinued treatment due to AEs, compared with 3.4% receiving placebo.

Conclusion: PGB significantly improved FM pain in patients with FM and co-morbid depression receiving concurrent antidepressant medication, when compared with placebo. The safety profile of PGB in this population was consistent with previous studies and current product labeling.

Disclosure: L. M. Arnold, Pfizer Inc, Eli Lilly and Company, Takeda , AstraZeneca, Forest Laboratories, Theravance, Pfizer Inc, Dainippon Sumitomo Pharma, Daiichi Sankyo, Theravance, Purdue Pharma L.P., Pfizer Inc ; P. Sarzi-Puttini, Abbvie, Bristol-Myers Squibb, Merck Sharp and Dohme, Pfizer Inc, Roche Pharmaceuticals ; P. Arsenault, Pfizer Inc, Janssen Pharmaceutica Product, L.P., Diex Research, Pfizer Inc, Janssen Pharmaceutica Product, L.P., Purdue Pharma L.P., Valeant, Eli Lilly and Company ; T. Khan, Pfizer Inc, Pfizer Inc ; P. Bhadra Brown, Pfizer Inc, Pfizer Inc ; A. Clair, Pfizer Inc, Pfizer Inc ; J. Driscoll, Pfizer Inc ; J. Landen, Pfizer Inc, Pfizer Inc; L. Pauer, Pfizer Inc, Pfizer Inc.