Saturday, 25 June 2011

Pfizer Says Lyrica Study Met Key Goal In Central Neuropathic Pain Treatment

(RTTNews) - Biopharmaceutical giant Pfizer Inc. (PFE: News ) Tuesday stated that its drug lyrica (pregabalin) met the primary endpoint of positive efficacy in reducing central neuropathic pain following spinal cord injury in a global phase 3 study. The company was announcing top-line results for the study.
Central neuropathic pain is a heterogeneous group of pain conditions initiated or caused by a primary lesion in the central nervous system. This pain often occurs following spinal cord injury.
Lyrica is currently approved in 110 countries and regions. In the U.S., lyrica capsules CV is approved to treat diabetic nerve pain, pain after shingles, fibromyalgia and partial onset seizures in adults with epilepsy who take one or more drugs for seizures. It is not approved to treat central neuropathic pain in the U.S.
According to Pfizer, the final stage lyrica study, A0081107, was a randomized, double-blind, placebo-controlled, parallel group, multi-center study, comparing pregabalin and placebo in subjects with chronic central neuropathic pain following traumatic spinal cord injury.
In the study, which was conducted in 66 investigative sites in 10 countries, pregabalin was flexibly dosed as 150-600mg/day or dosed twice daily. A total of 220 subjects were enrolled in the study.
The primary endpoint of the trial was the duration adjusted average change or DAAC, a weighted average of change in pain scores based on the duration a patient is participated in the study.

Combination Therapy Needed to Fight Chronic Pain

June 23, 2011 -- The last decade brought advances in our understanding of chronic pain, but this has not translated into better treatments yet, an analysis shows. The analysis was published in The Lancet.
It found that treatments for chronic, non-cancer pain such as low back pain, arthritis, headache, and fibromyalgia don't do enough to alleviate pain or restore functioning in the majority of people.
And don't expect any one pill to do the trick, says the report's author, Dennis C. Turk, PhD, an anesthesiologist and pain specialist at the University of Washington in Seattle. "There is this expectation that you will wave a wand and there will be a new pill or new surgery to alleviate your pain, and that is not likely to happen."
"Chronic pain is a complex problem, and the only way to treat it is with a combination of treatments because no one treatment is sufficient," he says. Combination therapy may mean multiple medications or medications plus lifestyle changes, psychological treatments, and/or rehabilitation and physical therapy.
Likening chronic pain to diabetes, Turk says "there are a lot of things to do in addition to medication, as in diabetes, where you also watch your weight and test your urine and blood."
It will involve a more holistic approach, he says. "We have a tendency to try to diagnose people in silos and treat everyone with knee osteoarthritis (OA) the same way," he says. But "we need to treat people as a whole and not just knees." Social, emotional, and environmental factors all play a role in how we experience pain and painful conditions.
One Treatment Not Always EnoughRoger Fillingim, PhD, associate professor in the College of Dentistry at the University of Florida in Gainesville, says that there have been advances in understanding the biology of pain and in awareness of pain as a pressing public health issue in recent years.
But "this hasn't translated into terribly effective treatments of chronic pain, and we will need more multidisciplinary treatments in order to provide more optimal clinical outcome for patients in pain," he says.
The truth is "for many forms of chronic pain, a single treatment is not sufficient to improve quality of life to the point where a patient will be satisfied," he says.
"That pill doesn't exist," he says. "There may be medication that helps alleviate some of the pain, but that needs to be accompanied by other treatments including physical rehabilitation and behavioral or psychological intervention to help people cope with their pain in a more effective manner."
Lesley Arnold MD, a psychiatrist at the University of Cincinnati, takes a more "glass is half-full" view of our accomplishments in treating chronic pain.
"We do have more options today," she says, citing several FDA approvals in recent years for new drugs to treat fibromyalgia and OA.  But "we do need more studies of combinations of medications to see what works well together and most importantly, we need studies looking at nondrug therapies."
"We don't have a good way of accessing the central nervous system to tell us why people are in pain," she says.

Saturday, 18 June 2011

Direct Medical Costs Are Double for Patients with Fibromyalgia

STUDY: Direct medical costs in patients with fibromyalgia: Cost of illness and impact of a brief multidisciplinary treatment program.
The patients diagnosed with fibromyalgia incur about twice as much direct medical costs than that of non fibromyalgia patients, according to the results of a 4-year study by the Department of Physical Medicine and Rehabilitation at the Mayo Clinic College of Medicine in Rochester, Minnesota. The study was published in the January 2011 issue of the American Journal of Physical Medicine & Rehabilitation.
The objective of the study was to compare the direct medical costs of clinically diagnosed patients with fibromyalgia with the medical costs of matched controls during a 4-yr period and to assess the impact of a fibromyalgia treatment program on healthcare utilization and associated medical costs. The study compared economic outcomes in 87 patients who participated in a fibromyalgia treatment program between 2001 and 2004 and who were local residents for the entire 4-yr period spanning their participation in the program, with age and sex-matched controls. Costs for the 2 yrs before and 2 yrs after program participation were also compared.
RESULTS: Four-year medical costs for controls were $7774 compared with $15,759 for those with fibromyalgia. There was no significant change in direct costs after participation in a brief fibromyalgia treatment program. Those with increased symptom severity averaged $2034 higher direct medical costs during the 4-yr period.
CONCLUSIONS: Patients with clinically diagnosed fibromyalgia incur direct medical costs about twice that of their matched controls. This increased cost is related to the severity of their symptoms as measured by the Fibromyalgia Impact Questionnaire and was not impacted by participation in a brief cognitive behaviorally based fibromyalgia treatment program.

HYPNOSIS: Efficacy of hypnosis/guided imagery in fibromyalgia syndrome

Author: Kathrin BernardyNicole FuberPetra KloseWinfried Hauser
Credits/Source: BMC Musculoskeletal Disorders 2011, 12:133

Recent systematic reviews on psychological therapies of fibromyalgia syndrome (FMS) did not consider hypnosis/guided imagery (H/GI). Therefore we performed a systematic review with meta-analysis of the efficacy of H/GI in FMS.

We screened, Cochrane Library, MEDLINE, PsycINFO and SCOPUS (through December 2010).
(Quasi-) randomized controlled trials (CTs) comparing H/GI with controls were analyzed. Outcomes were pain, sleep, fatigue, depressed mood and health-related quality of life (HRQOL).
Effects were summarized using standardized mean differences (SMD).

Six CTs with 239 subjects with a median of 9 (range 7-12) H/GI-sessions were analysed. The median number of patients in the H/GI groups was 20 (range 8-26).
Three studies performed follow-ups. H/GI reduced pain compared to controls at final treatment (SMD -1.17 [95% CI -2.21, -0.13]; p= 0.03.
H/GI did not reduce limitations of HRQOL at final treatment (SMD -0.90 [95% CI -2.55, 0.76]; p=0.29) compared to controls. Effect sizes on fatigue, sleep and depressed mood at final treatment and follow-up and on pain and HRQOL at follow-up were not calculated because of limited data available.
The significant effect on pain at final treatment was associated with low methodological and low treatment quality.

Further studies with better treatment quality and adequate methodological quality assessing all key domains of FMS are necessary to clarify the efficacy of H/GI in FMS.

CYCLOBENZAPRINE: Effects of Bedtime Very Low Dose (VLD) Cyclobenzaprine (CBP) on Symptoms and Sleep Physiology in Patients with Fibromyalgia Syndrome

Jun. 16, 2011
TONIX Pharmaceuticals, a specialty pharmaceutical company developing therapies for challenging disorders of the central nervous system, including Fibromyalgia Syndrome (FM) and Post-traumatic Stress Disorder (PTSD), presented sleep EEG (electroencephalogram) findings from a clinical study in which patients with FM were treated with very low dosage (VLD) cyclobenzaprine (CBP) at bedtime. The VLD CBP treated patients showed a decrease in pain, fatigue, tenderness and depressive symptoms and reported fewer of the side effects often associated with daytime CBP at higher doses. In the new findings, VLD CBP treatment improved sleep efficiency and increased the number of nights with reduced rates of EEG Cyclic Alternating Pattern (CAP) sleep types CAPA2 + CAPA3, which are associated with sleep instability and previously were shown to be elevated in FM patients. The findings were the subject of a poster presentation at the Associated Professional Sleep Societies 2011 Anniversary Meeting in Minneapolis, MN.
Dr. Harvey Moldofsky, President and Medical Director, Centre for Sleep and Chronobiology, Toronto, Canada, and lead author of the study, commented, “This study showed that a low dose of cyclobenzaprine taken at bedtime improves the widespread pain and tenderness in patients with fibromyalgia. It also provides a novel algorithm that identifies reductions in a specific EEG pattern of sleep instability that correlate with improvements in the nonrestorative sleep symptoms of fatigue and disturbed mood.”
“These new findings suggest that our technology for bedtime treatment of fibromyalgia with very low dose cyclobenzaprine confers benefits that have been associated with restful or restorative sleep,” stated President Seth Lederman, M.D., Chairman and President of TONIX.
About the Study
The study was a randomized, double-blind, placebo-controlled, dose-escalating parallel-design study in 36 patients with FM conducted at two Canadian sites. The study was analyzed with regard to efficacy, safety and tolerability as well as EEG and other parameters assessed during sleep. VLD CBP treated subjects showed significant improvements over eight weeks in pain, fatigue, tenderness, the Hospital Anxiety and Depression Scale (HAD), and sleep efficiency. In addition, VLD CBP was well tolerated, with no adverse events or discontinuations due to adverse events. The sleep EEG data were analyzed for the types of CAP: CAPA1 (associated with sleep stability) and CAPA2 + CAPA3 (usually associated with sleep instability). VLD CBP treatment increased EEG sleep nights with normalized CAPA2+A3, or CAPA2+A3(Norm) ≤ 33%. Increased nights of CAPA2+A3(Norm) ≤ 33% correlated with improvement in fatigue, total HAD score, HAD depression subscore, and self-rated and clinician-rated change in fatigue. In VLD CBP treated subjects, the correlation of increased nights of CAPA2+A3(Norm) ≤ 33% with improvement with FM symptoms is consistent with the hypothesized effects of restorative sleep. The symptomatic benefit may relate to VLD CBP decreasing arousal or alarm signals during sleep. CAPA2+A3(Norm) rate may provide a novel biomarker for assessing treatment effects on nonrestorative sleep and associated subjective somatic and mood symptoms in FM. The full abstract can be found at (# 0690).

About TONIX Pharmaceuticals
TONIX Pharmaceuticals is developing new treatments for challenging disorders of the central nervous system. The Company’s most advanced program targets fibromyalgia syndrome based on bedtime treatment with very low dosage cyclobenzaprine. Cyclobenzaprine in higher doses is the active ingredient of U.S. FDA approved muscle relaxants. Based on this foundation, the Company is building a deep and diverse pipeline of high-value medications for other syndromes, disorders and diseases, including post-traumatic stress disorder. For more information, please visit

DULOXETINE: Improvement in multiple dimensions of fatigue in patients with fibromyalgia treated with duloxetine: secondary analysis of a randomized, placebo-controlled trial

Author: Lesley ArnoldFujun WangJonna AhlPaula GaynorMadelaine Wohlreich
Credits/Source: Arthritis Research &Therapy 2011, 13:R86

Fatigue is one of the most disabling symptoms associated with fibromyalgia that greatly impacts quality of life. Fatigue was assessed as a secondary objective in a 2-phase, 24-week study in outpatients with American College of Rheumatology-defined fibromyalgia.

Patients were randomized to duloxetine 60-120 mg/d (N=263) or placebo (N=267) for the 12-week acute phase.
At Week 12, all placebo-treated patients were switched to double-blind treatment with duloxetine for the extension phase. Fatigue was assessed at baseline and every 4 weeks with the Multidimensional Fatigue Inventory (MFI) scales: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Activity, and Reduced Motivation.
Other assessments that may be associated with fatigue included: Brief Pain Inventory (BPI) average pain, numerical scales to rate anxiety, depressed mood, bothered by sleep difficulties, and musculoskeletal stiffness. Treatment-emergent fatigue-related events were also assessed.
Changes from baseline to Week 12, and from Week 12 to Week 24, were analyzed by mixed-effects model repeated measures analysis.

At Week 12, duloxetine versus placebo significantly (all p<.05) reduced ratings on each MFI scale, BPI pain, anxiety, depressed mood, and stiffness. Improvement in ratings of being bothered by sleep difficulties was significant only at Weeks 4 and 8.
At Week 24, mean changes in all measures indicated improvement was maintained for patients who received duloxetine for all 24 weeks (n=176). Placebo-treated patients switched to duloxetine (n=187) had significant within-group improvement in Physical Fatigue (Weeks 16, 20 and 24); General Fatigue (Weeks 20 and 24); Mental Fatigue (Week 20); and Reduced Activity (Weeks 20 and 24).
These patients also experienced significant within-group improvement in BPI pain, anxiety, depressed mood, bothered by sleep difficulties, and stiffness. Overall, the most common (>5% incidence) fatigue-related treatment-emergent adverse events were fatigue, somnolence, and insomnia.

Treatment with duloxetine significantly improved multiple dimensions of fatigue in patients with fibromyalgia, and improvement was maintained for up to 24 weeks.Trial Registration: Clinical Trial Registry NCT00673452.

Sunday, 12 June 2011

ICAF: Combined Index of Severity of Fibromyalgia

Fibromyalgia (FM) is a complex syndrome that affects many aspects of the patients life and it is very difficult to evaluate in clinical practice. A recent study has developed the Combined Index of Severity of Fibromyalgia (ICAF), an instrument that evaluates diverse aspects of FM and offers five indices: emotional, physical, active coping, passive coping and total.
The objective of this study is to confirm the structure of the ICAF, check its test-retest reliability, assess its sensitivity to change, and compare the results obtained in a sample of patients with fibromyalgia with another sample of healthy controls.
Methods: A total of 232 patients took part in the study, 228 women and 4 men, with a mean age of 47.73 years of age (SD=8.61) and a time of disease evolution since diagnosis of 4.28 years (SD=4.03). The patients from the FM group completed the ICAF.
Between one and two weeks later, they again attended the clinic and complete the 59 items on the ICAF (retest) and immediately afterwards they began treatment (according to daily clinical practice criteria). A sample of healthy subjects was also studied as a control group: 110 people were included (106 women and 4 men) with a mean age of 46.01 years of age (SD=9.35).
The study was conducted in Spain.
Results: The results obtained suggest that the four-factor model obtained in the previous study adequately fits the data obtained in this study. The test-retest reliability and internal consistency were all significant and show a high degree of correlation for all the factors as well as in overall score.
With the exception of the passive coping factor, all the other scores, including the overall score, were sensitive to change after the therapeutic intervention. The ICAF scores of the patients with fibromyalgia compared with those of the control group were markedly different.
Conclusions: The findings suggest that the ICAF is a valid, reliable, sensitive to change instrument with the added advantage that it offers some additional domains (factors) that provide very valuable information regarding the most delicate aspects of the patient, which must be addressed at the time of treatment in daily clinical practice.

Author: Miguel VallejoJavier RiveraJoaquim Esteve-VivesJavier RejasGroup Icaf
Credits/Source: Health and Quality of Life Outcomes 2011, 9:39

Placebo Effect

 Mark J. Pellegrino, MD*
June 8, 2011

It is not surprising that people with fibromyalgia are interested in alternative medicine approaches.

If there is one area in which conventional medicine often fails, it is in the management of conditions causing chronic pain.

Conventional medicine emphasizes the diagnosis and pharmacologic treatment of various medical conditions based on scientific research. The main philosophy is to identify the cause of the disease and treat it with medicines or surgeries to eliminate the cause. But if someone has chronic pain, does not respond to medications, is not a candidate for a surgical procedure, and has had numerous diagnostic tests that were normal, conventional medicine may be helpless.

Complementary or alternative medicine strategies emphasize the interaction between the body and the mind. The main focus is on maintaining homeostasis, which is the body's natural ability to maintain a stable harmony and balance among its hormones, enzymes, muscles, and organs to prevent disease or to allow the body to heal itself... And an increased number of scientific studies are being published that support the effectiveness of many complementary medicine treatments.

[But in fact] most conditions that doctors treat do not have scientific studies that "prove" a particular treatment is effective. That does not stop us from treating conditions, nor should it. Medical practitioners need to be open-minded. If we always waited for scientific proof, most diseases that exist would not be treated.

Placebo Effect

I remember learning that the placebo effect was “bad.” The placebo effect occurred when a person reported improvement in pain (or other symptoms) after being given a sugar pill instead of the actual drug (or other treatment).

The placebo effect has to be accounted for in any scientific research study because a placebo response does not measure the effect of the drug or treatment being tested. So as not to mistakenly attribute all of the positive benefits to the drug being tested to a placebo effect, research studies are designed to “cancel out” the placebo effect.

Placebo is derived from the Latin word that means “I will please.” It is a positive human response to hopefulness and wanting to get better with a treatment.

Even though the person wasn’t given an actual research drug, she or he felt measurably better simply because of HOPE.

Studies show the placebo effect may happen up to 30% of the time with any treatment. This means 3 of 10 people will feel better when given any type of treatment, with no obvious relationship to the actual treatment.

The placebo effect is a powerful physician “tool” that is not limited to a pill.

Suggestions that a physician makes can have a dramatic effect on how a patient will respond to a particular treatment.

In a study done by Drs. Staats and Hekmat (1998)(1), the role of one’s pain threshold in response to suggestion was examined. Three groups of college students were to place their hands in a tank of ice water. Each group was instructed differently.

• The first group was told “neutral” things: Don’t think about anything, just keep your hand in the water until you need to remove it.

• The second group was told “positive” things: Ice water can improve circulation, strengthen the heart, cleanse the skin cells, and other beneficial effects.

• The third group was told “negative” things: Ice water can be dangerous by causing numbness, decrease in blood flow, tissue damage and hypertension.

All three groups were told to keep their hands immersed until they couldn’t tolerate the pain any more.

Guess what happened? The “positive” group held their hands in longer and reported less anxiety. The “negative group took their hands out much quicker and reported more anxiety. The “neutral” group was in between the other groups.

This study demonstrated how the physician can affect the patient’s response to treatment.

Reassuring, positive words are more likely to increase the therapeutic response – cause a positive placebo response.

I have found much better responses to medications in my patients when I explain what to expect - and tell them the medicines may help but won’t take away all the pain – than if I just gave them the medicines and said, “Take this and let me know if it helps.”

A number of years ago it dawned on me that the placebo response from hopefulness and one’s desire to improve is EXACTLY what we are trying to accomplish in the treatment of chronic pain related to fibromyalgia. We want people to feel better, even if we can’t explain how it happened.

This approach would seem to be one of the major philosophies of complementary medicine - to improve the well-being of body and mind.

With this realization, I’ve washed out all of the negative connotations I learned about placebos from conventional medicine and have become more open-minded. Now one of my philosophies is: Welcome Placebo! We WANT to achieve a positive placebo response.

Sunday, 5 June 2011

Interference with work in fibromyalgia - effect of treatment with pregabalin and relation to pain response

Author: Sebastian StraubeR Andrew MooreJocelyn PaineSheena DerryCeri PhillipsErnst HallierHenry McQuay
Credits/Source: BMC Musculoskeletal Disorders 2011, 12:125

Clinical trials in chronic pain often collect information about interference with work as answers to component questions of commonly used questionnaires but these data are not normally analysed separately.

Methods: We performed a meta-analysis of individual patient data from four large trials of pregabalin for fibromyalgia lasting 8-14 weeks. We analysed data on interference with work, inferred from answers to component questions of Fibromyalgia Impact Questionnaire (FIQ), Short Form 36 Health Survey, Sheehan Disability Scale, and Multidimensional Assessment of Fatigue, including "How many days in the past week did you miss work, including housework, because of fibromyalgia?"from FIQ.
Analyses were performed according to randomised treatment group (pregabalin 150-600mg daily or placebo), pain improvement (0-10 numerical pain rating scale scores at trial beginning vs. end), and end of trial pain state (100mm visual analogue pain scale [VAS]).

Results: Comparing treatment group average outcomes revealed modest improvement over the duration of the trials, more so with active treatment than with placebo.
For the 'work missed'question from FIQ the change for patients on placebo was from 2.2 (standard deviation [SD] 2.3) days of work lost per week at trial beginning to 1.9 (SD 2.1) days lost at trial end (p<0.01). For patients on 600mg pregabalin the change was from 2.1 (SD 2.2) days to 1.6 (SD 2.0) days (p<0.001).
However, the change in days of work lost was substantial in patients with a good pain response: from 2.0 (SD 2.2) days to 0.97 (SD 1.6) days (p<0.0001) for those experiencing >/=50% pain improvement and from 1.9 (SD 2.2) days to 0.73 (SD 1.4) days (p<0.0001) for those achieving a low level of pain at trial end (<30mm on the VAS). Patients achieving both >/=50% pain improvement and a pain score <30mm on the VAS had the largest improvement, from 2.0 (SD 2.2) days to 0.60 (SD 1.3) days (p<0.0001).
Analysing answers to the other questions yielded qualitatively similar results.

Conclusions: Effective pain treatment goes along with benefit regarding work. A reduction in time off work >1 day per week can be achieved in patients with good pain responses.