Fibromyalgia Medication Image

Fibromyalgia is characterised by widespread musculoskeletal pain, fatigue, cognitive dysfunction, and sleep disturbances. It is a condition that affects around 3-4% of the population, and appears to be more prevalent in women. There is no cure for fibromyalgia, and current treatment strategies consist of symptom management; primarily, pain reduction. Analgesic drugs are most commonly used for fibromyalgia-associated pain, however, the effectiveness of these drugs is varied, and commonly they are ineffective. In addition to pharmacologic therapies, non-pharmacologic therapies used for treatment include exercise and stress management.

Although patients with fibromyalgia experience chronic musculoskeletal pain, there is no evidence of structural or functional anomalies of the muscle. What is becoming more evident is that patients have irregular functioning of pain processing mechanisms in the central nervous system. Specifically, amplification of pain signals may occur, increasing the sensitivity to pain. It has been reported that patients with fibromyalgia experience 50% more pain than healthy patients when exposed to the same painful stimulus. MRI studies have found that areas of the brain responsible for pain processing (eg amygdala, thalamus, and insula) have abnormal signalling in response to pain. In addition, levels of chemicals in the cerebrospinal fluid associated with pain signalling are also irregular in patients with fibromyalgia. It is likely that there is also a genetic component, since patients who have siblings affected by fibromyalgia have an increased risk of developing the disorder compared to the general population. A specific region on chromosome 17 has been associated with this familial link.

There are a large number of scientific and clinical studies that are aiming to improve knowledge and treatment of this disorder, thereby improving overall quality of life for patients suffering with fibromyalgia. The following is a brief report of some of the most recent clinical studies currently recruiting patients.

Transcranial Magnetic Stimulation

Transcranial magnetic stimulation is a procedure that influences the electrical activity in the brain by way of a pulse magnetic field. It is a safe and painless procedure that can be focused to target specific areas of the brain’s surface. The effects of transcranial magnetic stimulation are being studied in patients for treatment of pain associated with fibromyalgia. Studies are not only investigating the change in pain scores, but also the biochemical, functional, and structural changes in the brain following treatment. One study will also investigate the effects of transcranial magnetic stimulation in combination with rehabilitation exercise on pain in fibromyalgia patients. The investigators believe that the most beneficial effects will occur when both treatments are used in combination.

Pilot studies in fibromyalgia patients were shown to induce a 40% improvement in pain, which was maintained for up to three months. Further study will optimize the therapy intervals and duration for maximum benefit, and aim to discover the mechanisms by which pain reduction is achieved in this patient population.

Clinicaltrials.gov “Repetitive Transcranial Magnetic Stimulation in Fibromyalgia (STIMALGI)” Available from:http://www.clinicaltrials.gov/ct2/show/NCT01308801?term=fibromyalgia+AND+transcranial&recr=Open&no_unk=Y&rank=2 Last Accessed April 8, 2014.

Clinicaltrials.gov “Effects of Direct Transcranial Current Stimulation on Central Neural Pain Processing in Fibromyalgia” Available from: http://www.clinicaltrials.gov/ct2/show/NCT01745003?term=fibromyalgia+AND+transcranial&recr=Open&no_unk=Y&rank=3Last Accessed April 8, 2014.

Clinicaltrials.gov “Single-arm, Open-label, Phase II Trial of HD-tDCS in Fibromyalgia Patients” Available from: http://www.clinicaltrials.gov/ct2/show/NCT01842009?term=fibromyalgia+AND+transcranial&recr=Open&no_unk=Y&rank=4Last Accessed April 8, 2014.

Clinicaltrials.gov “Pain Sensitivity of Subjects With Fibromyalgia Before and After Repetitive Transcranial Magnetic Stimulation Treatment” Available from: http://www.clinicaltrials.gov/ct2/show/NCT01992822?term=fibromyalgia+AND+transcranial&recr=Open&no_unk=Y&rank=5Last Accessed April 8, 2014.

Clinicaltrials.gov “Efficiency of Repetitive Transcranial Magnetic Stimulation (rTMS) Sessions After a Successful 3 Week-treatment in Fibromyalgia” Available from: http://www.clinicaltrials.gov/ct2/show/NCT01942538?term=fibromyalgia+AND+transcranial&recr=Open&no_unk=Y&rank=6Last Accessed April 8, 2014.

Clinicaltrials.gov “A Prospective Trial to Explore the Efficacy of dTMS in Subjects With Fibromyalgia” Available from: http://www.clinicaltrials.gov/ct2/show/NCT02083588?term=fibromyalgia+AND+transcranial&recr=Open&no_unk=Y&rank=7Last Accessed April 8, 2014.

Pregabalin (Lyrica)

Pregabalin (Lyrica) is currently used for the treatment of pain associated with spinal cord injury, shingles, diabetic nerve pain, and fibromyalgia. It is also used to treat seizures in epileptics. Pregabalin inhibits the release of neurotransmitters, thereby reducing the overactive nerves that are responsible for causing pain or seizures.

Pfizer is currently conducting phase 3 and phase 4 clinical trials with pregabalin in several countries. Two of the trials will assess the safety, efficacy, and tolerability of pregabalin in adolescents aged 12-18 years, and the third will assess the safety, efficacy, and tolerability of pregabalin in adults. The studies will determine how effective pregabalin is at reducing fibromyalgia pain in different patient populations.

Clinicaltrials.gov “Adolescent Fibromyalgia Study” Available from: http://www.clinicaltrials.gov/ct2/show/NCT01020474?term=fibromyalgia+AND+pregabalin&recr=Open&no_unk=Y&rank=1Last Accessed April 8, 2014.

Clinicaltrials.gov “A Study For Pregabalin In Patients With Fibromyalgia”Available from: http://www.clinicaltrials.gov/ct2/show/NCT01387607?term=fibromyalgia+AND+pregabalin&recr=Open&no_unk=Y&rank=2Last Accessed April 8, 2014.

Clinicaltrials.gov “Pregabalin In Adolescent Patients With Fibromyalgia”Available from: http://www.clinicaltrials.gov/ct2/show/NCT01020526?term=fibromyalgia+AND+pregabalin&recr=Open&no_unk=Y&rank=4Last Accessed April 8, 2014.

Lyrica Information Sheet Available from: http://www.lyrica.comLast Accessed April 8, 2014.

Taylor CP, Angelotti T, Fauman E.“Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery.”Epilepsy Res. 2007 Feb;73(2):137-50.

Milnacipran (Savella)

Milnacipran is a norepinephrine-serotonin re-uptake inhibitor. Although preliminary studies have shown improvement in pain and physical function following treatment with milnacipran, the mechanisms involved are not very well understood. Forest Laboratories, in collaboration with the Cleveland Sleep Research Center, the University of Florida, and the University of California will be conducting three clinical trials to assess the effectiveness of milnacipran on pain reduction in patients suffering with fibromyalgia. In addition, one study will assess the effects milnacipran may have on sleep disturbance in fibromyalgia patients.

The studies will not only assess effectiveness on pain reduction, but will also attempt to identify some of the mechanisms by which this occurs, by measuring the levels of chemical neurotransmitters in the cerebrospinal fluid and plasma before and after treatment with milnacipran.

Clinicaltrials.gov“The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia”Available from: http://www.clinicaltrials.gov/ct2/show/NCT01234675?term=fibromyalgia+AND+milnacipran&recr=Open&no_unk=Y&rank=1Last Accessed April 8, 2014.

Clinicaltrials.gov “Effects of Milnacipran on Widespread Mechanical and Thermal Hyperalgesia of Fibromyalgia Patients” Available from: http://www.clinicaltrials.gov/ct2/show/NCT01294059?term=fibromyalgia+AND+milnacipran&recr=Open&no_unk=Y&rank=2Last Accessed April 8, 2014.

Clinicaltrials.gov “Effect of Milnacipran on Pain in Fibromyalgia (Forest)”Available from: http://www.clinicaltrials.gov/ct2/show/NCT01288807?term=fibromyalgia+AND+milnacipran&recr=Open&no_unk=Y&rank=3Last Accessed April 8, 2014.

Savella Information Sheet Available from: http://www.savella.comLast Accessed April 8, 2014.

Duloxetine (Cymbalta)

In preclinical studies duloxetine has demonstrated inhibition of neuronal serotonin and norepinephrine reuptake, and to a lesser extent, dopamine reuptake. The exact mechanism of action, however, is still under investigation.

At the University of California, duloxetine is currently in a phase 4 clinical trial for adults for pain reduction in fibromyalgia patients. Another area of study focus is to determine whether there are any markers in peripheral nerves that might be able to predict the therapeutic responsiveness to duloxetine. In this study, nerve histology will be examined by skin biopsy to determine if the nerve morphology is predictive of duloxetine effectiveness at reducing pain.

Duloxetine is also in phase 3 trials for adolescents aged 13-17 across the United States and parts of South America, by Eli Lily, to determine whether it is effective at reducing fibromyalgia pain in this patient group.

Clinicaltrials.gov “Cymbalta for Fibromyalgia Pain” Available from: http://www.clinicaltrials.gov/ct2/show/NCT01619566?term=fibromyalgia+AND+duloxetine&recr=Open&no_unk=Y&rank=1Last Accessed April 8, 2014.

Clinicaltrials.gov “A Study of Duloxetine in Adolescents With Juvenile Primary Fibromyalgia Syndrome” Available from:

http://www.clinicaltrials.gov/ct2/show/NCT01237587?term=fibromyalgia+AND+duloxetine&recr=Open&no_unk=Y&rank=2Last Accessed April 8, 2014.

Cymbalta Information Sheet Available from: www.cymbalta.comLast Accessed April 8, 2014.

 Image courtesy of David Castillo Dominici / FreeDigitalPhotos.net

Written by Deborah Tallarigo, PhD

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