Effects of Bedtime Very Low Dose Cyclobenzaprine on Symptoms and Sleep Physiology in Patients with Fibromyalgia Syndrome: A Double-blind Randomized Placebo-controlled Study

Abstract

Objective.To determine the effects of bedtime very low dose (VLD) cyclobenzaprine (CBP) on symptoms and sleep physiology of patients with fibromyalgia (FM), unrefreshing sleep, and the α-nonREM sleep electroencephalographic (EEG) anomaly at screening.Methods.Of 37 patients with FM in the screened population, 36 were randomized and treated in this 8-week, double-blind, placebo-controlled, dose-escalating study of VLD CBP 1–4 mg at bedtime. We evaluated changes in subjective symptoms including pain, tenderness, fatigue, mood [Hospital Anxiety and Depression Scale (HAD)], and objective EEG sleep physiology (at screening, baseline, and Weeks 2, 4, and 8).Results.In the VLD CBP-treated group (n = 18) over 8 weeks, musculoskeletal pain and fatigue decreased, tenderness improved; total HAD score and the HAD depression subscore decreased; patient-rated and clinician-rated fatigue improved. In the placebo-treated group (n = 18), none of these outcome measures changed significantly. Compared to placebo at 8 weeks, VLD CBP significantly improved pain, tenderness, and the HAD Depression subscore. Analysis of cyclic alternating pattern (CAP) sleep EEG revealed that significantly more subjects in the VLD CBP group than the placebo group had increased nights of restorative sleep in which CAPA2+A3/CAPA1+A2+A3= CAPA2+A3(Norm)≤ 33%. For VLD CBP-treated subjects, the increase in nights with CAPA2+A3(Norm)≤ 33% was correlated to improvements in fatigue, total HAD score, and HAD depression score.Conclusion.Bedtime VLD CBP treatment improved core FM symptoms. Nights with CAPA2+A3(Norm)≤ 33% may provide a biomarker for assessing treatment effects on nonrestorative sleep and associated fatigue and mood symptoms in persons with FM.

Fibromiyaljide Farmakolojik Tedavi

“…Beş tane randomize kontrollü çalışmanın değerlendirildiği bir metaanaliz sonuçlarına göre siklobenzaprin tedavisi alan toplam 392 fibromiyalji hastasının 4 ile 24. hafta sonuçları karşılaştırıldığında genel iyileşmenin plaseboya oranla üç kat daha fazla olduğu, ağrı ve uyku problemlerinde ılımlı düzelme sağladığı gösterilmiştir 56 . Yine 36 hastanın değerlendirildiği yeni bir randomize kontrollü çalışmada 8 hafta süresince düşük doz siklobenzaprin kullanımının uyku üzerine anlamlı düzelme sağladığı bildirilmektedir 57 .…”

Sleep as a Window into the World of Fibromyalgia Syndrome

“…The article by Moldofsky's group in this issue of The Journal suggests that CAP may be a useful biomarker for tracking treatment effects in FM 12 . Using cyclobenzaprine 1-4 mg, A2/A3 CAP normalized to total CAP appeared to be a useful biomarker that predicted positive treatment effects.…”

“…For example, the benzodiazepines and non-benzodiazepine GABA receptor modulators reduce CAP 12 , but do not seem to have unique clinical utility in FM. The effects of sodium oxybate 16 on EEG CAP would be interesting to know, although I predict there would be a reduction in A2/A3 CAP.…”

The Combination of Fibromyalgia and Obstructive Sleep Apnea Syndrome: A Case Report and Review of the Literature

“…In some studies, prevalence has been determined at almost 100% [6]. Sleep disorders include findings such as insomnia, waking during the night, restless sleep and inability to get up in the morning [7][8][9][10].…”