One reason antidepressant medication treatments do not work as well in real life as they do in clinical studies could be the limited type of study participants selected, researchers at UT Southwestern Medical Center have found.

“We are basing our judgment of clinical care in the United States on samples of patients that are totally different from the patient population actually treated in primary care and mental health facilities,” said Dr. Madhukar Trivedi, professor of psychiatry at UT Southwestern and senior author of a study published in the May issue of the American Journal of Psychiatry. “Antidepressants should not be seen as a panacea. The general belief is that they work well, but they are less effective in real-world practice, and more work is needed.”

As part of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study scientists found that only 22 percent of the 2,855 participants treated with a commonly prescribed antidepressant would have met the criteria for inclusion in a typical antidepressant efficacy trial. Those who did meet criteria had shorter bouts of depression, quicker response to medication, less severe side effects and fewer adverse events compared with those people with depression who would have been excluded from such a trial, used to gain Food and Drug Administration approval of the drugs used.

The STAR*D trial was the first large-scale study to define the effectiveness of several treatment steps in primary care and mental health settings for people with depression, Dr. Trivedi said.

The six-year, $35 million STAR*D study is the largest investigation on the treatment of major depressive disorder and is considered a benchmark in the field of depression research. It initially included more than 4,000 people from outpatient treatment sites across the country. About 65 percent of STAR*D participants, however, had a medical co-morbidity such as diabetes that typically would have excluded them from participating in other clinical trials to test the efficacy of antidepressants, said Dr. Trivedi, co-principal investigator of STAR*D.

“Evidence is growing that depression is like other chronic medical illnesses where it’s not just one small, short bout, but a longer battle. People with depression may be at higher risk for other illnesses including obesity or diabetes, yet people with these conditions are excluded from drug trials for depression,” Dr. Trivedi said.

STAR*D provided evidence for step-by-step guidelines to address treatment-resistant depression. Many treatment-resistant depression patients would be excluded from drug efficacy trials because those trials typically eliminate study candidates who have previously tried treatment, have suicidal thoughts or have other psychiatric illnesses.

“These are the patients impacted by depression the most - highest suicide potential, highest unemployment rates, highest social impairment - and they are likely to produce poorer outcomes,” Dr. Trivedi said. “That population doesn’t get studied systematically in traditional pharmaceutical industry studies.”

More research involving patients routinely seen in clinical practice coupled with pharmacogenetics is sorely needed to better understand how to best match patients with specific antidepressant treatments, Dr. Trivedi said.

He recommended that clinicians continue to prescribe antidepressants but with more realistic expectations about the disease’s long-term nature. Dr. Trivedi said researchers should design future trials in real clinical practice settings where patients have co-morbidities, as he is doing in his current research.

Other UT Southwestern researchers involved in the study were Dr. Mustafa Husain, professor of psychiatry and internal medicine; and Drs. Diane Warden and David Morris, both assistant professors of psychiatry. Researchers from seven other medical institutions were also involved.

STAR*D is funded by the National Institute of Mental Health. Antidepressant medications were provided by Bristol-Myers Squibb, Forest, GlaxoSmithKline , King Pharmaceuticals, Organon, Pfizer and Wyeth.

Dr. Trivedi has received consulting or speaking fees from Abbott, Abdi Brahim, Akzo (Organon), AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Fabre-Kramer, Forest, GlaxoSmithKline , Janssen, Johnson & Johnson, Meade Johnson, Neuronetics, Parke-Davis, Pfizer, Sepracor, Vantage-Point and Wyeth.

Source:
Lakisha Ladson

UT Southwestern Medical Center

Amarillo Biosciences, Inc. (ABI) (OTCBB: AMAR) announced that the screening of volunteers for inclusion in a Phase 2 clinical study of the company’s oral interferon product at the University of Western Australia is now complete. The investigators met their target of screening at least 200 healthy adults for participation in the trial. A total of 215 volunteers were evaluated and 134 of them have been enrolled into the study to date. About 90% of the screened subjects have been found to qualify for the study, so additional enrollments are expected over the next 2 weeks to bring the total number of study participants up to or above the targeted 160 subjects.

The double-blind, placebo-controlled Phase 2 clinical trial is being conducted by Dr. Manfred Beilharz and colleagues. The study is expected to show that lozenges containing a low dose of interferon-alpha can prevent infection or reduce the severity of infection with influenza and other common respiratory viruses when taken once a day during a typical winter cold/flu season.

Dr. Joseph Cummins, President and CEO of ABI, said, “We are pleased that Dr. Beilharz and his study team were able to achieve their goal of screening over 200 volunteers because this study is an important step in proving that our low-dose interferon lozenges can be a safe and effective alternative to antiviral drugs for influenza. New therapies like oral interferon are needed in the face of the ongoing swine flu pandemic, especially since the influenza virus has developed resistance in the past to currently marketed antiviral drugs.”

Dr. Manfred Beilharz said, “The community spread of swine flu in Perth has gone from 0 to 80+ in 14 days, and that is only the confirmed cases. Over the next 3 months we here in Perth, Western Australia may well experience a reproduction of the community spread that is occurring in Melbourne, Victoria. If our lozenges work as well as we anticipate against swine flu, we will make a tremendous contribution to economical public health procedures.”

Source
Amarillo Biosciences

Researchers from the Brigham and Women’s Hospital and Harvard Medical School in Boston have released a 22-year study that reports Hispanic patients have poorer outcomes following infrainguinal bypass grafting for the treatment of peripheral arterial disease (PAD). Results showed that of all the study participants, Hispanics had a higher rate of bypass graft failure and amputation after revascularization compared to Caucasians. In an analysis that accounted for a myriad of important variables affecting limb salvage after bypass, Hispanic ethnicity was found to be independently predictive of eventual amputation. Details of the study appear in the Society for Vascular Surgery’s(R) June 2009 issue of the Journal of Vascular Surgery(R).

“Despite our attempts to treat all patients very aggressively for severe lower extremity ischemia through revascularization to prevent amputation, limb preservation at five years was 80 percent in Hispanics, 84 percent in African-Americans, and a 91 percent in Caucasians,” said Michael Belkin, MD, chief of the division of vascular and endovascular surgery.

Researchers said they embarked on this study when they noticed some of the Hospital’s Hispanic patients seemed to demonstrate an aggressive form of PAD that was difficult to treat with infrainguinal bypass grafting, the “gold standard” for severe lower extremity ischemia. They also said there was very little information available about PAD in the Hispanic population and, in particular, little data on the outcomes of lower extremity bypass grafting in these patients.

Dr. Belkin explained that 1,646 consecutive patients who participated in the study (1,408 Caucasians, 57 Hispanics and 181 African-Americans) underwent autogenous infrainguinal reconstructions. He added Hispanic patients, like African-Americans counterparts, often required a bypass at younger age and more commonly had diabetes in comparison to Caucasians. African-Americans and Hispanics also had severe atherosclerosis below the level of knee and therefore required bypass operations lower down the leg, which are more technically demanding.

In comparison to Caucasians, “Hispanics required additional interventional procedures or operations to maintain adequate blood flow through these grafts,” said Dr. Belkin. “From our analysis of factors which contribute to graft failure, it appears that a preponderance of young patients and females, both known risk factors for graft failure, in our Hispanic population may have contributed to the initial graft failures in these patients.”

In addition to Hispanic ethnicity, independent predictors of eventual limb loss included the severity of ischemia at presentation: comorbidities including diabetes and chronic renal insufficiency, female gender, age of less than 65 years, and the use higher-risk conduit or bypass.

Medication use (including antiplatelet drugs and anticoagulants) as well as surgical approach was equivalent between groups, and there were no differences in technical success, short-term complication rates or surveillance for problems in these bypass grafts between ethnicities.

This study is important, according to researchers, because Hispanics are the fastest growing demographic in the United States (currently at 45 million and expected to grow to 103 million by 2050) and comprise 25 percent of the U.S. population.

“Our data provides evidence of outcome disparities in Hispanics treated aggressively for PAD,” said Dr. Belkin. “Further investigation with regard to biologic and social factors is required to delineate the reasons for these inferior outcomes in Hispanic patients.”

About Journal of Vascular Surgery®

Journal of Vascular Surgery provides vascular, cardiothoracic and general surgeons with the most recent information in vascular surgery. Original, peer-reviewed articles cover clinical and experimental studies, noninvasive diagnostic techniques, processes and vascular substitutes, microvascular surgical techniques, angiography and endovascular management. Special issues publish papers presented at the annual meeting of the Journal’s sponsoring society, the Society for Vascular Surgery.

Source: Society for Vascular Surgery