Posts Tagged ‘medication’

A new study by researchers at University of Maryland School of Medicine has identified promising compounds that could successfully treat depression in less than 24 hours while minimizing side effects. Although they have not yet been tested in people, the compounds could offer significant advantages over current antidepressant medications.

The research, led by Scott Thompson, PhD, Professor and Chair of the Department of Physiology at the University of Maryland School of Medicine (UM SOM), was published this month in the journal Neuropsychopharmacology.

“Our results open up a whole new class of potential antidepressant medications,” said Dr. Thompson. “We have evidence that these compounds can relieve the devastating symptoms of depression in less than one day, and can do so in a way that limits some of the key disadvantages of current approaches.”

Currently, most people with depression take medications that increase levels of the neurochemical serotonin in the brain. The most common of these drugs, such as Prozac and Lexapro, are selective serotonin reuptake inhibitors, or SSRIs. Unfortunately, SSRIs are effective in only a third of patients with depression. In addition, even when these drugs work, they typically take between three and eight weeks to relieve symptoms. As a result, patients often suffer for months before finding a medicine that makes them feel better. This is not only emotionally excruciating; in the case of patients who are suicidal, it can be deadly. Better treatments for depression are clearly needed.

Dr. Thompson and his team focused on another neurotransmitter besides serotonin, an inhibitory compound called GABA. Brain activity is determined by a balance of opposing excitatory and inhibitory communication between brain cells. Dr. Thompson and his team argue that in depression, excitatory messages in some brain regions are not strong enough. Because there is no safe way to directly strengthen excitatory communication, they examined a class of compounds that reduce the inhibitory messages sent via GABA. They predicted that these compounds would restore excitatory strength. These compounds, called GABA-NAMs, minimize unwanted side effects because they are precise: they work only in the parts of the brain that are essential for mood.

The researchers tested the compounds in rats that were subjected to chronic mild stress that caused the animals to act in ways that resemble human depression. Giving stressed rats GABA-NAMs successfully reversed experimental signs of a key symptom of depression, anhedonia, or the inability to feel pleasure. Remarkably, the beneficial effects of the compounds appeared within 24 hours – much faster than the multiple weeks needed for SSRIs to produce the same effects.

“These compounds produced the most dramatic effects in animal studies that we could have hoped for,” Dr. Thompson said. “It will now be tremendously exciting to find out whether they produce similar effects in depressed patients. If these compounds can quickly provide relief of the symptoms of human depression, such as suicidal thinking, it could revolutionize the way patients are treated.”

In tests on the rats’ brains, the researchers found that the compounds rapidly increased the strength of excitatory communication in regions that were weakened by stress and are thought to be weakened in human depression. No effects of the compound were detected in unstressed animals, raising hopes that they will not produce side effects in human patients.

“This work underscores the importance of basic research to our clinical future,” said Dean E. Albert Reece, MD, PhD, MBA, who is also the vice president for Medical Affairs, University of Maryland, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean of the School of Medicine. “Dr. Thompson’s work lays the crucial groundwork to transform the treatment of depression and reduce the tragic loss of lives to suicide.”

http://www.news-medical.net/news/20150714/New-study-identifies-potential-antidepressant-medications-with-few-side-effects.aspx

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A provocative new study suggests that more than 80 percent of people with depression in the general population aren’t eligible for clinical trials of antidepressant drugs.

Researchers comment that at least five patients would need to be screened to enroll just one patient meeting the typical inclusion and exclusion criteria for antidepressant registration trials (ARTs).

Drs. Sheldon Preskorn and Matthew Macaluso of University of Kansas School of Medicine-Wichita and Dr. Madhukar Trivedi of Southwestern Medical School in Dallas led the study.

The investigation illuminates some major differences between patients with depression seen in everyday clinical practice and those enrolled in ARTs. This awareness is meaningful as ARTs commonly lead to FDA drug approval for depression medications.

The study appears in the Journal of Psychiatric Practice.

Antidepressant registration trials use certain inclusion and exclusion criteria to create a group of patients with similar characteristics. These criteria increase the chances of detecting true drug effects, while reducing “false signals” of safety problems or side effects.

For example, ARTs commonly exclude patients with other medical problems — if their illness worsened during the study, it might raise inaccurate safety concerns about the drug being studied.

To find out how these inclusion and exclusion criteria affect patient selection for ARTs, the researchers analyzed more than 4,000 patients from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.

Funded by the National Institute of Mental Health, STAR*D was the largest and longest study of depression treatment ever conducted. To ensure that the “real world” population of patients with depression was represented, STAR*D used minimal exclusion criteria.

The researchers found that more than 82 percent of STAR*D patients would not be eligible for enrollment in current ARTs, based on a list of “usual” inclusion and exclusion criteria. Fourteen percent would be excluded on the basis of age alone–that’s because most ARTs exclude patients older than 65. Another 15 percent would be excluded because their depression was less severe than a commonly used cutoff point.

More than 20 percent of STAR*D patients would be excluded from ARTs because of a “clinically significant or unstable general medical condition.” Twenty-one percent of women would be excluded because they were not using birth control to prevent pregnancy during the study.

Because many ARTs use stricter criteria, the true exclusion rate is probably even higher, the authors note.

For example, more recent studies have used even higher severity thresholds for enrollment, which would eliminate more than 90 percent of the STAR*D population. The researchers also point out that all of the STAR*D patients had obviously agreed to participate in that research study — which is something many people with depression might be unwilling to do.

The researchers hope their work will help drug developers understand how inclusion and exclusion criteria may affect enrollment in ARTs, and help them in developing an appropriate recruitment plan and timeline.

“The timelines in most drug studies are unrealistically short and their recruitment plans are often woefully inadequate, resulting in studies that take longer than expected to complete and frequent budget overruns,” the researchers write.

Failure to consider the effort needed for ART recruitment might lead to lost revenue, delays in bringing a drug to market, or failure to develop a potentially effective medication.

The findings may also help to explain to healthcare practitioners why ARTs tend to overestimate the benefits of antidepressant treatment in “real world” patients with depression. “Obviously,” the researchers add, “the more patients who are excluded from the ARTs, the greater the chances that the results will not generalize to the routine clinical practice.”

http://psychcentral.com/news/2015/07/15/antidepressant-clinical-trials-exclude-many-people-with-depression/86887.html

Results of a small study suggest that Parkinson’s patients seem to improve if they think they’re taking a costly medication. The findings have been published online Jan. 28 in Neurology.

In the study, 12 patients had their movement symptoms evaluated hourly, for about four hours after receiving each of the placebos. On average, patients had bigger short-term improvements in symptoms like tremor and muscle stiffness when they were told they were getting the costlier of two drugs. In reality, both “drugs” were nothing more than saline, given by injection. But the study patients were told that one drug was a new medication priced at $1,500 a dose, while the other cost just $100 — though, the researchers assured them, the medications were expected to have similar effects.

Yet, the researchers found that when patients’ movement symptoms were evaluated in the hours after receiving the fake drugs, they showed greater improvements with the pricey placebo. What’s more, magnetic resonance imaging scans showed differences in the patients’ brain activity, depending on which placebo they’d received. The patients in the study didn’t get as much relief from the two placebos as they did from their regular medication, levodopa. But the magnitude of the expensive placebo’s benefit was about halfway between that of the cheap placebo and levodopa. What’s more, patients’ brain activity on the pricey placebo was similar to what was seen with levodopa.

And this effect is “not exclusive to Parkinson’s,” according to Peter LeWitt, M.D., a neurologist at the Henry Ford West Bloomfield Hospital in Michigan, who wrote an editorial published with the study. Research has documented the placebo effect in various medical conditions, he told HealthDay. “The main message here is that medication effects can be modulated by factors that consumers are not aware of — including perceptions of price.”

http://www.empr.com/pricey-placebo-works-better-than-cheaper-one-in-parkinsons-study/article/395255/?DCMP=EMC-MPR_DailyDose_rd&CPN=edgemont14,emp_lathcp&hmSubId=&hmEmail=5JIkN8Id_eWz7RlW__D9F5p_RUD7HzdI0&dl=0&spMailingID=10518237&spUserID=MTQ4MTYyNjcyNzk2S0&spJobID=462545599&spReportId=NDYyNTQ1NTk5S0