Addition of Lyrica Significantly Improved Generalized Anxiety Disorder Symptoms in Patients Who Responded Only Partially to Previous GAD Treatments

From the FMS Global News Desk of Jeanne Hambleton (UK)

First Large, Placebo-Controlled Study to Demonstrate Efficacy of Lyrica as Add-on Therapy Strategy in Difficult-to-Treat GAD Patients

May 19, 2009 03:00 PM Eastern Daylight Time

SAN FRANCISCO–(BUSINESS WIRE)–The addition of Pfizer’s Lyrica® (pregabalin) capsules CV to other generalized anxiety disorder (GAD) treatments significantly improved the symptoms of the condition in patients who responded only partially to previous treatments, according to a study presented today at the American Psychiatric Association annual meeting in San Francisco, Ca. In this study, patients treated with Lyrica showed significant improvements in both their psychological and physical symptoms of anxiety.

Generalized anxiety disorder is a chronic, debilitating anxiety disorder affecting nearly seven million Americans and is characterized by persistent, excessive, uncontrollable worry about everyday things. Patients also frequently experience physical symptoms such as muscle tension, fatigue, sleep disturbance, and other aches and pains.

The condition is complex and often difficult to treat, with 40 percent to 60 percent of patients failing to achieve remission after six months of treatment in clinical studies with serontonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) – two common classes of FDA-approved GAD treatments.

“These data are very encouraging for the high percentage of GAD patients who still struggle with debilitating symptoms despite treatment,” said Dr. Rakesh Jain, one of the study’s investigators and director, adult and child psycho-pharmacology research, R/D Clinical Research, Inc. “It is clear we need additional effective, well-tolerated options to address this difficult to treat condition.”

This is the first large, placebo-controlled trial to demonstrate the efficacy of an add-on therapy strategy in patients who had failed to respond to two different courses of GAD monotherapy with a SSRI, SNRI or benzodiazepine.

The study found that patients treated with Lyrica in addition to their baseline SSRI/SNRI therapy had a significantly greater improvement in overall anxiety symptoms as well as individual psychological and physical symptoms compared to baseline therapy alone as measured by the Hamilton Anxiety Scale (HAM-A), an interview scale that measures the severity of a patient’s anxiety. Over the eight week treatment period, patients receiving add-on Lyrica therapy had, on average, an anxiety score that was 1.2 points lower on the HAM-A compared to baseline therapy alone (P=0.012).

Significantly more patients receiving add-on Lyrica treatment (50 percent) showed at least a 50 percent reduction in their anxiety symptoms compared to SSRI/SNRI treatment alone (37 percent) (P=0.023). Lyrica was also shown to be well tolerated as an add-on therapy in this study.

About the Study

This study was a double-blind, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of adjunctive Lyrica in 353 patients with a primary diagnosis of GAD. To be included in the study, patients had to have a HAM-A score greater or equal to 22, and to have not responded, or only minimally responded, to treatment with a SSRI, SNRI or benzodiazepine prior to the study.

These patients were then treated with a different SSRI/SNRI for eight weeks. At the end of the eight week open-label treatment period, patients who had shown only a partial response to treatment (as defined by a HAM-A score of greater than or equal to 16, less than 50 percent decrease in HAM-A score, and a Clinical Global Impression Improvement score of less than 3) were then randomized to an additional eight weeks of double-blind treatment with either Lyrica (150 to 600 mg/day) or placebo while continuing treatment with the existing background SSRI or SNRI therapy.

The primary endpoint was the mean change score on the Hamilton Anxiety Rating Scale. The SSRIs and SNRIs used in this study included escitalopram, paroxetine and venlafaxine XR.

The most common side effects in the study compared to other GAD treatments plus placebo were dizziness (11.7 percent vs. 5.7 percent), headache (9.4 percent vs. 4 percent), and somnolence (8.3 percent vs. 3.4 percent).

This study was sponsored by Pfizer, Inc.

About Lyrica

In the United States, Lyrica is approved for the management of fibromyalgia, painful diabetic peripheral neuropathy, postherpetic neuralgia (pain after shingles), and for the adjunctive treatment of partial onset seizures (a type of epilepsy) in adults. Lyrica is not approved for GAD in the U.S.

Outside of the United States, Lyrica is indicated in adults for the management of peripheral and central neuropathic pain, treatment of generalized anxiety disorder, and adjunctive therapy for partial seizures with or without secondary generalization.

Important Safety Information

Treatment with Lyrica may cause dizziness, somnolence, peripheral edema or blurred vision. Other most common adverse reactions include dry mouth, weight gain, constipation, euphoric mood, balance disorder, increased appetite and thinking abnormally. There have been post-marketing reports of angioedema and hypersensitivity. Like other anti-epileptic drugs, Lyrica may cause suicidal thoughts or actions in a very small number of people.

Pfizer Inc: Working together for a healthier world™

Founded in 1849, Pfizer is the world’s premier biopharmaceutical company taking new approaches to better health. We discover, develop, manufacture and deliver quality, safe and effective prescription medicines to treat and help prevent disease for both people and animals. We also partner with healthcare providers, governments and local communities around the world to expand access to our medicines and to provide better quality health care and health system support. At Pfizer, more than 80,000 colleagues in more than 90 countries work every day to help people stay happier and healthier longer and to reduce the human and economic burden of disease worldwide.

DISCLOSURE NOTICE: The information contained in this release is as of May 19, 2009. Pfizer assumes no obligation to update any forward-looking statements contained in this release as the result of new information or future events or developments.

This release contains forward-looking information about the use of Lyrica for GAD, including its potential benefits, that involves substantial risks and uncertainties. Such risks and uncertainties include, among other things, the uncertainties inherent in research and development; decisions by the Food and Drug Administration (FDA) regarding whether and when to approve any supplemental drug application that may be filed for a GAD indication for Lyrica as well as the FDA’s decisions regarding labeling and other matters that could affect its availability or commercial potential; and competitive developments.

A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2008 and in its reports on Form 10-Q and Form 8-K.

(Contacts: Pfizer Inc Media: Sally Beatty, 212-733-6566
Permalink: http://www.businesswire.com/news/home/20090519006509/en)

FOR MORE FIBROMYALGIA STORIES SEE http://jeannehambleton77.wordpress.com

Gulf War Veterans Display Abnormal Brain Response to Specific Chemicals

From the FMS Global and UK News Desk of Jeanne Hambleton

Courtesy of Newswise Science Centre -UT Southwestern Medical Center
Dallas March 20 2009

Newswise — A new study by UT Southwestern Medical Center researchers is the first to pinpoint damage inside the brains of veterans suffering from Gulf War syndrome – a finding that links the illness to chemical exposures and may lead to diagnostic tests and treatments.

Dr. Robert Haley, chief of epidemiology at UT Southwestern and lead author of the study, said the research uncovers and locates areas of the brain that function abnormally. Recent studies had shown evidence of chemical abnormalities and shrinkage of white matter in the brains of veterans exposed to certain toxic chemicals, such as sarin gas during the 1991 Persian Gulf War.

The research, published in the March issue of the journal Psychiatry Research: Neuroimaging, enables investigators to visualize exact brain structures affected by these chemical exposures, Dr. Haley said.

“Before this study, we did not know exactly what parts of the brain were damaged and causing the symptoms in these veterans,” he said. “We designed an experiment to test areas of the brain that would have been damaged if the illness was caused by sarin or pesticides, and the results were positive.”

In designing the study, Dr. Haley and his colleagues reasoned that if low-level sarin or pesticides had damaged Gulf War veterans’ brains, a likely target of the damage would be cholinergic receptors on cells in certain brain structures. If that was so, administering safe levels of medicines that stimulate cholinergic receptors would elicit an abnormal response in ill veterans.

In the study, 21 chronically ill Gulf War veterans and 17 well veterans were given small doses of physostigmine, a substance which briefly stimulates cholinergic receptors. Researchers then measured the study participants’ brain cell response with brain scans.

“What we found was that some of the brain areas we previously suspected responded abnormally to the cholinergic challenge,” Dr. Haley said. “Those areas were in the basal ganglia, hippocampus, thalamus and amygdala, and the thalamus. Changes in functioning of these brain structures can certainly cause problems with concentration and memory, body pain, fatigue, abnormal emotional responses and personality changes that we commonly see in ill Gulf War veterans.”

A previous study funded by the U.S. Army found that repetitive exposure to low-level sarin nerve gas caused changes in cholinergic receptors in lab rats.

“An added bonus is a statistical formula combining the brain responses in 17 brain areas that separated the ill from the well veterans, and three different Gulf War syndrome variants from each other with a high degree of accuracy,” Dr. Haley said. “If this finding can be repeated in a larger group, we might have an objective test for Gulf War syndrome and its variants.”

An objective diagnostic test, he said, sets the stage for ongoing genetic studies to see why some people are affected by chemical exposures, and why others are not. New studies would also allow the selection of homogenous groups of ill veterans in which to run efficient clinical trials for treatments.

Dr. Haley first described Gulf War syndrome in a series of papers published in January 1997 in the Journal of the American Medical Association. In previous studies, research from Dr. Haley showed that veterans suffering from Gulf War syndrome had lower levels of a protective blood enzyme called paraoxonase, which usually fights off the toxins found in sarin. Veterans who served in the same geographical area and did not get sick had higher levels of this enzyme.

Dr. Haley and his colleagues have closely followed the same group of tests subjects since 1995. In 2006, UT Southwestern and the Department of Veterans Affairs established a dedicated, collaborative Gulf War illness research enterprise in Dallas, managed by UT Southwestern.

Texas Sen. Kay Bailey Hutchison, a longtime supporter of Gulf War research, facilitated that agreement and secured a $75 million appropriation over five years for Gulf War illness research.

This study was funded, in part, by the U.S. Army Medical Research and Materiel Command.

Other UT Southwestern researchers involved in the current study included Drs. Jeffrey Spence and Patrick Carmack, assistant professors of clinical sciences; Drs. Michael Devous and Frederick Bonte, professors of radiology; and Dr. Madhukar Trivedi, professor of psychiatry. Researchers from Southern Methodist University also participated.

Dr. Robert Haley http://www.utsouthwestern.edu/findfac/professional/0,2356,12888,00.html
(Article -http://www.utsouthwestern.edu/utsw/cda/dept353744/files/522139.html)