The effects of pregabalin on sleep disturbance symptoms among individuals with fibromyalgia syndrome

Russell, I. Jon; Crofford, Leslie J.; Leon, Teresa; Cappelleri, Joseph C.; Bushmakin, Andrew G.; Whalen, Ed; Barrett, Jeannette A.; Sadosky, Alesia

doi:10.1016/j.sleep.2009.01.009

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Volume 10, Issue 6 , Pages 604-610, June 2009

The effects of pregabalin on sleep disturbance symptoms among individuals with fibromyalgia syndrome

I. Jon Russell
- University Clinical Research Center, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., MC7868, San Antonio, TX 78229, USA
Leslie J. Crofford
- Division of Rheumatology & Women’s Health, University of Kentucky, Room J-503 Kentucky Clinic, 740 S. Limestone, Lexington, KY 40536, USA
Teresa Leon
- Pfizer Global Pharmaceuticals, 235 E. 42nd Street, New York, NY 10017, USA
Joseph C. Cappelleri
- Pfizer Inc, Global Research and Development, 50 Pequot Avenue, New London, CT 06320, USA
Andrew G. Bushmakin
- Pfizer Inc, Global Research and Development, 50 Pequot Avenue, New London, CT 06320, USA
Ed Whalen
- Pfizer Global Pharmaceuticals, 235 E. 42nd Street, New York, NY 10017, USA
Jeannette A. Barrett
- Pfizer Global Pharmaceuticals, 235 E. 42nd Street, New York, NY 10017, USA
Alesia Sadosky
- Pfizer Inc, Global Outcomes Research, 235 East 42nd Street, New York, NY 10017, USA
- Corresponding author. Tel.: +1 212 733 9491: fax: +1 646 441 4757.

Received 24 October 2008; received in revised form 23 January 2009; accepted 31 January 2009.

Abstract

Objectives

Sleep disturbances are common in patients with fibromyalgia (FM). The objective of this analysis was to evaluate the effects of pregabalin on sleep in patients with FM.

Methods

Analyses were based on two randomized, double-blind, placebo-controlled trials of pregabalin (300mg, 450mg, and 600mg daily) in adult FM patients. Sleep outcomes included the Medical Outcomes Study (MOS) Sleep Scale and a daily diary assessment of sleep quality. Treatment effects were evaluated using analysis of covariance. Clinically important differences (CID) in the Sleep Quality Diary and MOS Sleep Disturbance scores were estimated using mixed-effects models of changes in scores as a function of patients’ global impressions of change. Mediation modeling was used to quantify the direct treatment effects on sleep in contrast to indirect influence of the treatment on sleep via pain.

Results

A total of 748 and 745 patients were randomized in the respective studies. Patients were predominantly Caucasian females, average age 48–50 years, on average had FM for 9–10 years, and experienced moderate to severe baseline pain. Pregabalin significantly improved the Sleep Quality Diary (P<0.001), MOS Sleep Disturbance (P<0.01), MOS Quantity of Sleep (P<0.003), and MOS Sleep Problems Index scores (P<0.02) relative to placebo. Treatment effects for the 450mg and 600mg groups exceeded the estimated CID thresholds of 0.83 and 7.9 for the Sleep Quality Diary and MOS Sleep Disturbance scores, respectively. Mediation models indicated that 43–80% of the benefits on sleep (versus placebo) were direct effects of pregabalin, with the remainder resulting from an indirect effect of treatment via pain relief.

Conclusions

These data demonstrate improvement in FM-related sleep dysfunction with pregabalin therapy. The majority of this benefit was a direct effect of pregabalin on the patients’ insomnia, while the remainder occurred through the drug’s analgesic activity.

Keywords: Fibromyalgia syndrome, Pregabalin, Pain, Sleep disturbance, Insomnia, MOS Sleep Scale, Clinically important difference, Mediation analysis