A Chilly Court: Alaska Attacks Lilly Over Zyprexa

This is the Zyprexa trial we’re talking about. The state, you may recall, sued Lilly in 2006, alleging the drugmaker failed to warn of weight gain and diabetes caused by Zyprexa, and wants Lilly to cover treatment costs of Medicaid patients who suffered serious health problems.

The civil suit is being closely watched by state and federal prosecutors investigating the drugmaker, because this is the first lawsuit filed by a state against Lilly to make it to trial. The outcome - and even the evidence - could, therefore, influence settlement talks under way with the US Attorney in Phildelphia and state attorneys general. An unfavorable verdict could also prompt other states to file lawsuits, although eight others already have done so. (By the way, if you want to read the controversial Zyprexa documents, visit Furious Seasons).

For its part, Lilly argues the state has two irreconcilable positions - at the same time Alaska is suing the drugmaker, the state continues to seek court orders to force mental patients to take the very drug it says is harmful. These are the slides Lilly’s lawyers used in court.

READ MORE @ PHARMALOT

Low Risk, Heavy Drugs - State's Nursing Homes Might Be Overusing Antipsychotics

Connecticut's nursing homes dole out antipsychotic drugs to residents who do not have psychotic disorders at one of the highest rates in the country, raising questions about whether the medications are being used to subdue agitated patients because of a lack of staffing and attention to alternate treatments.

Federal data from the Centers for Medicare & Medicaid Services show that since 2005, Connecticut has consistently ranked in the top four states in the prevalence of antipsychotic drugs dispensed to nursing home residents who have no psychotic or related conditions. In the most recent quarterly report, through September 2007, only Louisiana had a higher prevalence rate than Connecticut, where more than 26 percent of residents who lacked an appropriate psychiatric diagnosis were prescribed antipsychotics.

Nationally, the prevalence rate is 19.8 percent, with several states, such as Florida, Pennsylvania and New Jersey, well below that average.

"This is not a good indicator" for Connecticut, said Charlene Harrington, an expert on nursing home quality and professor of sociology and nursing at the University of California-San Francisco. "One of the main factors [for a high medication rate] is not having enough staff. If patients are having behavioral problems, it's easier to give them a pill to keep them quiet" than to hire more staff. "It's cheaper. They'll sleep a lot."

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House Approves Bill on Mental Health Parity

After more than a decade of struggle, the House on Wednesday passed a bill requiring most group health plans to provide more generous coverage for treatment of mental illnesses, comparable to what they provide for physical illnesses.

The vote was 268 to 148, with 47 Republicans joining 221 Democrats in support of the measure.

The Senate has passed a similar bill requiring equivalence, or parity, in coverage of mental and physical ailments. Federal law now allows insurers to discriminate, and most do so, by setting higher co-payments or stricter limits on mental health benefits.

“Illness of the brain must be treated just like illness anywhere else in the body,” said Speaker Nancy Pelosi, Democrat of California. Supporters of the House bill, including consumer groups and the American Psychiatric Association, said it would be a boon to many of the 35 million Americans who experience disabling symptoms of mental disorders each year.

READ MPRE @ NY TIMES

ADHD Drugs Won't Raise Risk of Substance Abuse

Parents of children who are prescribed psychostimulants for attention deficit-hyperactivity disorder (ADHD) might have one less thing to worry about now that a new study concludes these kids are no more likely than their peers to abuse drugs and alcohol as young adults.

The report, which was funded by the National Institutes of Health, is published in the March issue of the American Journal of Psychiatry.

"The results should reassure clinicians who might be hesitant to treat ADHD because of concerns about future substance abuse," said study co-author Michael C. Monuteaux, assistant director of research at the pediatric psychopharmacology program at Massachusetts General Hospital.

Past research looking for a link between ADHD medications and substance abuse has produced conflicting conclusions.

"Some previous studies showed an increased risk of substance abuse associated with stimulant treatment, and other studies showed both no association and also a protective effect from treatments," Monuteaux said. "But those studies had some methodological limitations, and not all of them followed their samples well into late adolescence and early adulthood."

READ MORE @ US NEWS & WORLD REPORT

Comparison of antipsychotic treatments in adolescents with schizophrenia

There is a wealth of scientific literature available on the treatment of adults diagnosed with schizophrenia. However, there is a paucity of data to guide the treatment of children and adolescents with schizophrenia. “Although the U.S. Food and Drug Administration (FDA) has recently approved the use of aripiprazole and risperidone for adolescents with schizophrenia, few controlled data are available to help guide clinicians regarding the management of children and adolescents with schizophrenia who fail to respond to these standard 'first-line' antipsychotic treatments,” according to Dr. Sanjiv Kumra. Dr. Kumra is one of the authors of a new study to be published in the March 1st issue of Biological Psychiatry, which was undertaken to help fill this gap in knowledge.

The authors recruited 39 children, 10-18 years of age, who had already failed to respond to at least two antipsychotic treatments, to participate in a 12-week, double-blind, randomized study – the most rigorous of clinical trial designs. After initial assessments, the patients received treatment with either clozapine or “high-dose” olanzapine (doses that exceed the package insert recommendations) and were monitored for improvement in their symptoms. The researchers discovered that clozapine was approximately twice as likely to produce a treatment response as olanzapine. Both positive symptoms (psychosis) and negative symptoms (blunted emotional response, reduced motivation) responded better to clozapine. John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, comments on the findings: “Olanzapine is among the most effective antipsychotic medications, so the distinctive effectiveness of clozapine in this study could be very important.”

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Depressed Teens More Likely To Get Better With Switch To Combination Therapy

More than half of teenagers with the most debilitating forms of depression that do not respond to treatment with selective serotonin reuptake inhibitors (SSRIs) show improvement after switching to a different medication combined with cognitive behavioral therapy, researchers at UT Southwestern Medical Center and their colleagues in a multicenter study have found.

Dr. Graham Emslie, professor of psychiatry and pediatrics at UT Southwestern and chief of child and adolescent psychiatry at Children's Medical Center Dallas, was a principal investigator in the study appearing in the Journal of the American Medical Association.

Adolescents with treatment-resistant depression have unique needs, for which standard treatments do not always work. "If an adolescent hasn't responded to an initial treatment, go ahead and switch treatments," said Dr. Emslie. "Our results should encourage clinicians to not let an adolescent stay on the same medication and still suffer."

The 334 study participants suffered from depression on average for about two years. The teenagers involved exhibited moderate to severe major depressive disorder, many with suicidal ideation. Historically, these types of patients have the worst treatment outcomes.

READ MORE @ SCIENCE DAILY

Shape Abnormalities Found In Thalamus Of Siblings Of Schizophrenia Patients

Subtle malformations in the shape of the thalamus in the brain are generally found in schizophrenic patients -- and their healthy siblings appear to display the same abnormalities, according to a study published on June 6, 2007 in The Journal of Neuroscience.

Scientists at the Silvio Conte Center for the Neuroscience of Mental Disorders at Washington University School of Medicine in St. Louis performed MRI scans of the brains of 25 patients with schizophrenia, as well as their non-affected siblings. These scans were compared to those of 40 healthy volunteers and their siblings. A process that converts the two-dimensional images of the scan into three-dimensional models of brain anatomy, also known as high-dimensional brain mapping, was used to detect tiny differences in the anatomy of the brain.

"We're interested in the thalamus because it has a lot of connections to the prefrontal cortex," states Michael P. Harms, Ph.D., senior scientist at the Conte Center. " In addition to psychosis, schizophrenia is characterized by other difficulties, such as issues with working memory and decreased cognitive performance. Those symptoms are believed to involve the cortex, and since the thalamus projects throughout the cortex, it's conceivable abnormalities in the thalamus may be related to those symptoms."

READ MORE @ MEDICAL NEWS TODAY

F.D.A. Approves Wyeth Antidepressant

Faced with the looming loss of patent protection for its top-selling drug, the antidepressant Effexor XR, Wyeth received federal approval on Friday for a successor drug, Pristiq, which the company hopes will also become a blockbuster.

With the Food and Drug Administration’s approval of Pristiq, Wyeth said the company planned a big sales effort to introduce the product to psychiatrists and primary care doctors.

Wyeth needs a product that will replace some of the revenue expected to be lost to generic competitors of Effexor XR, whose patent protection expires in 2010. Sales of Effexor XR last year were $3.8 billion.

Dr. Philip Ninan, a Wyeth vice president for neuroscience, said he thought that Pristiq, which is chemically similar to Effexor, would have similar benefits in treating major depression. But the company said the drug had distinct advantages over its existing product.

Among them are that patients can start taking Pristiq at the therapeutic dose of 50 milligrams. Frequently, antidepressants must be started at a low dose, then ramped up to the therapeutic dose, to test whether patients can tolerate the drug and to determine the correct dose for the individual. Another advantage is that Pristiq does not have to be broken down by the liver, Dr. Ninan said, so it is not likely to interact with other medications metabolized by the liver.

READ MORE @ NY TIMES

Antidepressant drugs don't work – official study

They are among the biggest-selling drugs of all time, the "happiness pills" that supposedly lift the moods of those who suffer depression and are taken by millions of people in the UK every year.

But one of the largest studies of modern antidepressant drugs has found that they have no clinically significant effect. In other words, they don't work.

The finding will send shock waves through the medical profession and patients and raises serious questions about the regulation of the multinational pharmaceutical industry, which was accused yesterday of withholding data on the drugs.

REAS MORE @ THE INDEPENDENT

Mental acuity in seniors improving, study suggests

The brain function of Americans 70 and older appears to be improving, according to a study that found a smaller percentage of seniors with serious memory and language problems in 2002 than in 1993.

The finding, which researchers say is still preliminary, parallels an improvement in physical functioning among older Americans that is well documented.

"If this study is indeed confirmed and replicated, then it says that cognitive decline associated with aging is malleable," said Richard Suzman, director for behavioral and social research at the National Institute on Aging, which helped fund the study. "There may be interventions that can be brought to bear to accelerate the trend. It's potentially very good news."

Although the study does not mean that every individual will live healthier into old age, it does suggest that as a whole, people are functioning at a higher level for longer periods. That could mean that more people will be able to live independently later in life, said Suzman.

READ MORE @ BOSTON GLOBE

Anti-depressants' 'little effect'

New generation anti-depressants have little clinical benefit for most patients, research suggests.

A University of Hull team concluded the drugs actively help only a small group of the most severely depressed.

Marjorie Wallace, head of the mental health charity Sane, said that if these results were confirmed they could be "very disturbing".

But the makers of Prozac and Seroxat, two of the commonest anti-depressants, said they disagreed with the findings.

A spokesman for GlaxoSmithKline, which makes Seroxat, said the study only looked at a "small subset of the total data available".

READ MORE @ BBC

Researchers explore the antidepressant effects of ketamine

Drug treatments for depression can take many weeks for the beneficial effects to emerge. The excruciating and disabling nature of depression highlights the urgency of developing treatments that act more rapidly. Ketamine, a drug used in general medicine as an anesthetic, has recently been shown to produce improvements in depressed patients within hours of administration. A new study being published in the February 15th issue of Biological Psychiatry provides some new insight into the mechanisms by which ketamine exerts its effects.

Ketamine is classified as an N-methyl d-aspartate (NMDA) glutamate receptor antagonist. Maeng and colleagues now provide new evidence that these antidepressant effects of NMDA receptor antagonists are mediated by their ability to increase the stimulation of á-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptors. In other words, their findings indicate that the antidepressant-like effects of drugs like ketamine are dependent on AMPA receptor stimulation. This suggests that drugs that enhance AMPA receptor function might have rapid antidepressant properties.

Dr. Husseini Manji, corresponding author on this paper and a Deputy Editor of Biological Psychiatry, explains that “by aiming new medications at more direct molecular targets, such as NMDA or AMPA, we may be able to bypass some of the steps through which current antidepressants indirectly exert their effects — a roundabout route that accounts for the long time it takes for patients to begin feeling better with the conventional medications.” He adds, “Today’s antidepressant medications eventually end up doing the same thing, but they go about it the long way around, with a lot of biochemical steps that take time. Now we’ve shown what the key targets are and that we can get at them rapidly.”

http://www.eurekalert.org/pub_releases/2008-02/e-ret022108.php">READ MORE @ EUREKALERT

SCIENTISTS who develop drugs are familiar with disappointment — brilliant theories that don’t pan out or promising compounds derailed by unexpected side effects. They are accustomed to small steps and wrong turns, to failure after failure — until, in a moment, with hard work, brainpower and a lot of luck, all those little failures turn into one big success.

For Darryle D. Schoepp, that moment came one evening in October 2006, while he was seated at his desk in Indianapolis.

At the time, he was overseeing early-stage neuroscience research at Eli Lilly & Company and colleagues had just given him the results from a human trial of a new schizophrenia drug that worked differently than all other treatments. From the start, their work had been a long shot. Schizophrenia is notoriously difficult to treat, and Lilly’s drug — known only as LY2140023 — relied on a promising but unproved theory about how to combat the disorder.

When Dr. Schoepp saw the results, he leapt up in excitement. The drug had reduced schizophrenic symptoms, validating the efforts of hundreds of scientists, inside and outside of Lilly, who had labored together for almost two decades trying to unravel the disorder’s biological underpinnings.

READ MORE @ NY TIMES

Daring to Think Differently About Schizophrenia - New York Times

Antidepressants Can Help With Obsessive Compulsive Disorder

Common antidepressant drugs such as Prozac and Zoloft can be effective treatment options for obsessive compulsive disorder (OCD), according to a new review of studies.

Patients who take selective serotonin reuptake inhibitors, or SSRIs, are twice as likely to get some relief from their OCD symptoms as those who take placebo pills are.

However, the drugs have a "modest" effect at best, said Dr. Ghulam Mustafa Soomro, lead review author and honorary research fellow at St. George's Hospital Medical School in London.

"Although SSRIs should be considered potentially effective treatments for OCD patients, treatment decisions need to take account of the potential adverse effects of these drugs," including nausea, insomnia and sexual dysfunction, he warned.


READ MORE @ MEDICAL NEWS TODAY

F.D.A. Seeks to Broaden Range of Use for Drugs

When federal drug regulators approve a medicine for sale, they limit how drug makers sell it. A drug approved to treat only breast cancer cannot be marketed for lung cancer even if some studies suggest that the medicine may save lung patients.

But the Food and Drug Administration proposed guidelines Friday that would change this, and advocates on both sides of the issue say that lives are at stake.

The rules would allow drug and device makers to provide doctors with copies of medical journal articles that discuss product uses that have not been vetted or approved by the F.D.A. The rules also say that drug companies do not have to promise to adequately test the unapproved use discussed in the article.

Advocates of the rule say the F.D.A. is so slow in assessing drug and device benefits that companies need to be able to hand out medical journal articles so that doctors can learn immediately about life-saving uses.

“The consequence of rapid disclosure of these benefits could be measured in lives,” said Dr. Scott Gottlieb, a former F.D.A. deputy commissioner.

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As depression symptoms improve with antidepressants, hopelessness can linger

A sense of hopefulness does not improve as quickly as other symptom

People taking medication for depression typically see a lot of improvements in their symptoms during the first few months, but lagging behind other areas is a sense of hopefulness, according to new research from the University of Michigan Health System.

That means people with depression may still feel a sense of hopelessness even while their condition is improving, which could lead them to stop taking the medication.

For many in the study, feelings of hopefulness did not improve until several weeks, or even months, after depressive symptoms lifted, says lead author James E. Aikens, Ph.D., associate professor in the Department of Family Medicine at the University of Michigan Health System.

“The finding suggests that some patients may become unduly pessimistic and stop adhering to an already-helpful therapy,” he notes. This finding is troubling, he says, because hopelessness is a strong risk factor for suicide.

The study appears in the January-February issue of the journal General Hospital Psychiatry.

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Schizophrenia Drug’s Dosage Drives Success

The Vanderbilt physician who in the late 1980s established the antipsychotic drug clozapine as the gold standard for treating patients with treatment-resistant schizophrenia has improved on his own research.

Herbert Meltzer, M.D., director of the Schizophrenia Program in the Department of Psychiatry, and colleagues have shown that the success of clozapine in treating this population was not due to the unique pharmacologic features of the drug itself, but the fact that it was used at higher doses than what is used to treat patients with schizophrenia who respond well to antipsychotic drugs. Clozapine is rarely used for the 70 percent of patients whose psychotic symptoms respond well to a wide array of other antipsychotic drugs.

The study, published in the Jan. 23 issue of The Journal of Clinical Psychiatry and funded by Eli Lilly, included 40 men and women, ages 18 to 58, diagnosed with schizophrenia or schizoaffective disorder, which many think is part of the same spectrum of illness. Patients were recruited from three U.S. outpatient community mental health treatment facilities, including Nashville's Centerstone Mental Health Center.

The results showed that the drug olanzapine, whose pharmacology is considered closer to clozapine than that of any other drug available, when used at a higher dose than the established norm, is as effective as clozapine in improving psychopathology and cognition in treatment-resistant patients. The study showed that treatment-resistant patients taking higher doses respond more slowly than average patients taking conventional doses. In fact, both need to be given for six months before a good treatment response occurs, compared to six weeks for the average patient at the lower dose range.

READ MORE @ NEWSWISE MEDICAL NEWS

Midlife Suicide Rises, Puzzling Researchers

Shannon Neal can instantly tell you the best night of her life: Tuesday, Dec. 23, 2003, the Hinsdale Academy debutante ball. Her father, Steven Neal, a 54-year-old political columnist for The Chicago Sun-Times, was in his tux, white gloves and tie. “My dad walked me down and took a little bow,” she said, and then the two of them goofed it up on the dance floor as they laughed and laughed.

A few weeks later, Mr. Neal parked his car in his garage, turned on the motor and waited until carbon monoxide filled the enclosed space and took his breath, and his life, away.

Later, his wife, Susan, would recall that he had just finished a new book, his seventh, and that “it took a lot out of him.” His medication was also taking a toll, putting him in the hospital overnight with worries about his heart.

Still, those who knew him were blindsided. “If I had just 30 seconds with him now,” Ms. Neal said of her father, “I would want all these answers.”

Mr. Neal is part of an unusually large increase in suicides among middle-aged Americans in recent years. Just why thousands of men and women have crossed the line between enduring life’s burdens and surrendering to them is a painful question for their loved ones. But for officials, it is a surprising and baffling public health mystery.

READ MORE @ NY TIMES

Sex differences in the brain's serotonin system

A new thesis from he Swedish medical university Karolinska Institutet shows that the brain’s serotonin system differs between men and women. The scientists who conducted the study think that they have found one of the reasons why depression and chronic anxiety are more common in women than in men.

Serotonin is a brain neurotransmitter that is critical to the development and treatment of depression and chronic anxiety, conditions that, for reasons still unknown, are much more common in women than in men. A research group at Karolinska Institutet has now shown using a PET scanner that women and men differ in terms of the number of binding sites for serotonin in certain parts of the brain.

Their results, which are to be presented in a doctoral thesis by Hristina Jovanovic at the end of February, show that women have a greater number of the most common serotonin receptors than men. They also show that women have lower levels of the protein that transports serotonin back into the nerve cells that secrete it. It is this protein that the most common antidepressants (SSRIs) block.

“We don’t know exactly what this means, but the results can help us understand why the occurrence of depression differs between the sexes and why men and women sometimes respond differently to treatment with antidepressant drugs,” says associate professor Anna-Lena Nordström, who led the study.

The group has also shown that the serotonin system in healthy women differs from that in women with serious premenstrual mental symptoms. These results suggest that the serotonin system in such women does not respond as flexibly to the hormone swings of the menstrual cycle as that in symptom-free women.

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