Could better quality sleep reduce the pain of fibromyalgia and the painful memories in post-traumatic stress disorder (PTSD)?
More and more evidence shows a connection between pain and poor sleep quality; just recently, for example, this website reported results from the 2015 Sleep in America Poll conducted by the National Sleep Foundation. Only 37% of respondents with chronic pain and 45% of those with acute pain reported “good or very good” sleep quality, compared to 65% of those reporting no pain.1
If you are like most fibromyalgia or PTSD patients, your sleep is either fitful or unsatisfying.
Consider a classic study performed by Dr. Harvey Moldofsky at the University of Toronto. He enrolled college students and kept them awake for three days. After day three, almost all the students started to hurt all over. That’s right: they developed the key symptoms of fibromyalgia.2
We now understand that the inability to get restorative sleep plays an important role in the widespread pain that is the central complaint in fibromyalgia.
Indeed, the vast majority of fibromyalgia and PTSD patients complain of poor sleep quality.
Yet in the year 2015, there is no drug approved by the FDA that targets the sleep component of either of these two conditions. This has some people scratching their heads since the role of sleep in alleviating pain—underscored by the new Sleep in America Poll results—has been known for a long time.
Spurred by this need, our company is investigating a treatment to improve sleep quality and address the pain component of fibromyalgia and painful memories in PTSD.
We are developing TNX-102 SL as a bedtime treatment for fibromyalgia and PTSD that targets sleep quality. TNX-102 SL is a sublingual formulation of the FDA-approved muscle relaxant cyclobenzaprine, a compound that has been indicated for short term use as a muscle relaxant (Flexeril) since 1977.
TNX-102 SL is intended to be used every night for long-term treatment and is a lower dose of cyclobenzaprine that has not been approved for any indications including as a muscle relaxant.
Cyclobenzaprine works in the brain, and we believe its principal action in fibromyalgia and PTSD is via its interaction with receptors that are known to affect sleep quality. A TNX-102 SL tablet is placed under the tongue where it dissolves and releases cyclobenzaprine, which is absorbed directly across the mucous membrane in the mouth into the patient’s bloodstream. It is designed to be taken at bedtime, so as to begin to work as the patient falls asleep. The potential advantage of the low dosage chosen for development is for improving sleep quality while minimizing next-morning grogginess.
The sublingual formulation of TNX-102 SL delivers optimal blood level effect when taken as part of the bedtime ritual. We believe that by promoting better-quality sleep, we can make a meaningful difference in the symptoms experienced by those with fibromyalgia and PTSD.
Should TNX-102 SL improve sleep quality in fibromyalgia and PTSD, it would be a tool to understand the mysteries of sleep physiology and sleep disorders and to dissect the roles of disturbed sleep in the chronicity of pain and the recurrence of painful memories.
This could become a new therapy for those with fibromyalgia, whose symptoms can include chronic diffuse musculoskeletal pain, increased pain sensitivity at multiple tender points and abnormal pain processing.
Patients have reported dissatisfaction with the current standard of care. As for opiates and prescription sleep drugs, they have proven largely unsatisfactory.
Our Phase 2b BESTFIT (BEdtime Sublingual TNX-102 SL a Fibromyalgia Intervention Therapy) study of TNX-102 SL identified a therapeutic dose and its clinical benefit in FM will be studied in our phase 3 program. A phase 3 study (AFFIRM) will be initiated in in the second quarter of 2015.
We are also studying TNX-102 SL PTSD.
Poor sleep quality in PTSD is manifested by sleep disturbances such as nightmares, nighttime anxiety attacks, and difficulty falling or staying asleep.
Many people with PTSD experience chronic pain in addition to painful memories, but pain is not considered an integral part of PTSD. Sertraline and paroxetine are the only FDA-approved products for PTSD, but their use can be limited by side effects. Other anti-anxiety and sleep medicines are sometimes prescribed, but prescription anxiety drugs called benzodiazepines are contraindicated in PTSD and prescription sleep medicines are not ideal. In January, we announced that the first participant in the AtEase study had received medication. The AtEase study is a Phase 2 randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of TNX-102 SL in people with military-related PTSD and similar conditions. Sleep quality in these participants will be evaluated as one of the secondary endpoints in this study.
We continue to believe the principal action of cyclobenzaprine in fibromyalgia and PTSD is via its interaction with receptors that are known to affect sleep quality. Sleep quality data from our phase 2b study validated this unique pharmacological action of cyclobenzaprine.
Further research will undoubtedly give us even better insights into the relationship between sleep quality and pain—and how enhancing the former can reduce the latter.
Seth Lederman, MD is co-founder, CEO and chairman of Tonix Pharmaceuticals Holding Corp., a clinical-stage pharmaceutical company dedicated to the development of novel medicines for common yet challenging disorders of the central nervous system, including fibromyalgia, post-traumatic stress disorder (PTSD), and episodic tension-type headache.
2. Moldofsky H, et al. Chronobiological influences on fibromyalgia syndrome: theoretical and therapeutics implications. Baillieres Clin Rhematol. 1994 Nov;8(4):801-810.