Background Depression is often comorbid with fibromyalgia (FM) and many FM patients (pts) take antidepressants for their depression. Managing FM pain in these pts is important.
Objectives To determine the efficacy and safety of pregabalin (PGB) for FM pain in FM pts taking a serotonin specific reuptake inhibitor (SSRI) or a serotonin/norepinephrine reuptake inhibitor (SNRI) for comorbid depression.
Methods This was a randomized, 2-way crossover, double-blind, placebo (PBO)-controlled study comprising two 6-week treatment periods separated by a 2-week, single-blind taper/washout phase. Pts were randomized 1:1 to PGB/PBO or PBO/PGB. PGB starting dose was 150mg/d, optimized to 300 or 450mg/d (twice-daily allocation). Stable SSRI or SNRI medication was taken throughout. The primary efficacy endpoint was mean pain score (0–10 numeric rating scale) based on the mean of the last 7 daily pain scores. Secondary endpoints included: number of 30% and 50% pain responders; Hospital Anxiety and Depression Scale – Anxiety and Depression (HADS-A and HADS-D); Fibromyalgia Impact Questionnaire (FIQ); Subjective Sleep Questionnaire (SSQ); Patient Global Impression of Change (PGIC); and EuroQoL 5-Dimension (EQ-5D).
Results 197 pts were randomized; 181 received ≥1 dose of PGB and 177 PBO. At baseline, 84 (43.5%) pts had major depressive disorder, 101 (52.3%) depression not otherwise specified and 8 (4.2%) dysthymia; the mean ± SD HADS-D score was 8.0±3.6, indicating mild depression. 101 (52.3%) pts were taking an SSRI and 92 (47.7%) an SNRI; the commonest were duloxetine (31.6%) and citalopram (16.6%). The mean ± SD pain score was 6.7±1.2. At endpoint, the least squares mean ± SE pain score was significantly lower with PGB (4.84±0.15) vs. PBO (5.45±0.16; difference -0.61; 95% confidence interval [CI] -0.91,-0.31; p=0.0001). Mean pain scores were significantly lower with PGB in pts taking an SSRI (difference -0.48; 95% CI -0.89,-0.07; p=0.0211) or an SNRI (difference -0.76; 95% CI -1.21,-0.31; p=0.0012). Significantly more PGB- vs. PBO-treated pts were 30% (45.3% vs. 27.7%; p=0.0007) and 50% (26.0% vs. 15.8%; p=0.0205) pain responders. PGB also significantly improved HADS-D (difference -0.88; 95% CI -1.37,-0.39; p=0.0005), HADS-A (difference -0.95; 95% CI -1.40,-0.50; p<0.0001), FIQ total score (difference -6.60; 95% CI -9.33,-3.87; p<0.0001) and 3 of 5 measures of the SSQ (p<0.05 for each) vs. PBO. More pts were PGIC responders (very much/much improved) with PGB (46.2%) vs. PBO (30.1%) at the end of period 1 (p=0.0637). EQ-5D was similar with PGB and PBO (p=0.3854). Adverse events (AEs) occurred in 77.3% and 59.9% of PGB- and PBO-treated pts, respectively; the most frequent with PGB were dizziness (28.2%) and somnolence (19.9%). 4 serious AEs were reported, 3 (1.7%) with PGB and 1 (0.6%) with PBO; none were considered related to treatment. 6.1% of PGB-treated pts discontinued due to AEs vs. 3.4% receiving PBO.
Conclusions In pts with FM taking an SSRI or SNRI for comorbid depression, PGB significantly improved FM pain vs. PBO. The safety profile of PGB in these pts was consistent with previous studies and current product labelling.
Acknowledgements This study was funded by Pfizer Inc. Medical writing support was provided by David Cope PhD, of Engage Scientific Solutions, and funded by Pfizer Inc.
Disclosure of Interest : P. Sarzi-Puttini Consultant for: Abbvie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer Inc, Roche, L. Arnold Consultant for: Pfizer Inc, Eli Lilly and Company, Takeda, AstraZeneca, Forest Laboratories, Theravance, Dainippon Sumitomo Pharma, Daiichi Sankyo, Purdue Pharma L.P., Shire and Tonix Pharmaceuticals, P. Arsenault Consultant for: Pfizer Canada, Speakers bureau: Pfizer Inc, Purdue Pharma, Valeant Pharmaceuticals, Eli Lilly and Company and Janssen (Canada), T. Khan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, P. Bhadra Brown Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, A. Clair Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Scavone Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Driscoll Consultant for: Pfizer Inc, J. Landen Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Pauer Shareholder of: Pfizer Inc, Employee of: Pfizer Inc