Drug-Drug Interactions, Other Factors Can Affect Antipsychotic Treatment Regimens: Presented at ECNP

Inhibitors or inducers of the cytochrome (CY) P450 system may affect the metabolism and activity of antipsychotic drugs, according to a study presented September 13 at the 22nd European College of Neuropsychopharmacology (ECNP) Congress.

Pierre Chue, MD, Department of Psychiatry, University of Alberta, Edmonton, Alberta, and colleagues performed an evidence-based review of all relevant literature to identify and define possible drug-drug interactions (DDIs) and other factors that may influence patient response to drug treatment.

Comorbidities such as smoking, alcohol, other substance-abuse disorders, infections, and metabolic disorders complicate the pharmacological management of psychotic patients. Additional factors such as genetic polymorphisms and environmental interactions (eg, DDIs and drug-food interactions) also influence drug efficacy. The researchers noted that clinicians need to consider these factors and others, along with patients' unique characteristics, when determining treatment.

EWAD MORE @ DOCTOR'S GUUIDE

Treatment guidelines issued on depression during pregnancy

For women with serious conditions, medication may be the best route, but 'talk therapy' may alleviate suffering for others, according to a document prepared by two national physicians groups.

For the nearly one in four women who experience symptoms of depression during pregnancy, physicians on the front lines have long had little more than a prescription for antidepressants and a massive dose of uncertainty to offer.

The result: At last count, roughly 13% of pregnant women in the United States took antidepressant medications at some point in their pregnancy -- often with little to guide them in weighing the risks the drugs may pose to their fetus against the misery and dangers of untreated depression.

In a bid to resolve that conundrum, two of the nation's leading physicians groups have issued the first guidelines for the treatment of depression during pregnancy.

READ MORE @ LOS ANGELES TIMES

Metabolic Side Effects, Cardiovascular Risk Differs Among Antipsychotic Treatments for Schizophrenia: Presented at ECNP

The differences in metabolic side effects and cardiovascular risk resulting from antipsychotics make the initial choice of medication important in controlling long-term effects from treatments used for schizophrenia, researchers said here at the 22nd European College of Neuropsychopharmacology (ECNP) Congress.

W. Wolfgang Fleischhacker, MD, Biological Psychiatry Department, Medical University Innsbruck, Innsbruck, Austria, and colleagues analysed data from the European First Episode Schizophrenia Trial (EUFEST) study to determine the effects of several first- and second-generation antipsychotics on cardiovascular risk factors in patients with or without metabolic syndrome (MS) risk. Results of the study were presented on September 14.

READ MORE @ DOCTOR'S GUIDE

Glaxo Executive’s Memo Suggested Burying Drug Studies (Update4)

An executive of GlaxoSmithKline Plc, the world’s second-biggest drugmaker, talked about burying negative studies linking its antidepressant drug Paxil to birth defects, according to a company memo introduced at a trial.

“If neg, results can bury,” Glaxo executive Bonnie Rossello wrote in a 1997 memo on what the company would do if forced to conduct animal studies on the drug. The memo was read during opening statements in the trial of a lawsuit brought by the family of a child born with heart defects.

The Philadelphia trial is the first of more than 600 cases alleging that London-based Glaxo knew Paxil caused birth defects and hid those risks to pump up profits. The drug, approved for U.S. use in 1992, generated about $942 million in sales last year, 2.1 percent of Glaxo’s total revenue.

The family of Lyam Kilker claims Glaxo withheld information from consumers and regulators about the risk of birth defects and failed to properly test Paxil. Kilker’s mother, Michelle David, blames Paxil for causing life-threatening heart defects in her 3-year-old son.

Glaxo officials urged scientists to withhold information about Paxil’s risks from a paper laying out the company’s “core safety philosophy” for the drug, said Sean Tracey, a lawyer for Kilker and David, in his opening statement in the trial.

READ MORE @ BLOOMBERG

The future of schizophrenia

Press conference at the 22nd Congress of the European College of Neuropsychopharmacology, Sept. 14, 2009, Istanbul, Turkey

Schizophrenia is a major public health problem. Affecting almost 1% of the world's population, it takes an enormous economic and social toll in addition to the distress, dysfunction, disability and mortality for those afflicted with this disease. Elements of the disease are present from birth, other aspects emerge during developmental years, and the illness becomes fully expressed in early adulthood with long-lasting implications for most patients.

Schizophrenia, which is seen as the paradigmatic psychiatric illness, presents different symptoms in multiple domains, whereby positive and negative phenomena can be separated (Falkai et al., 2005): Positive (psychotic) symptoms in a broader sense include delusions or delusional ideation, hallucinations, disturbance of association, catatonic symptoms, agitations as well as feelings of alien influence and suspiciousness. Negative symptoms include restricted range and intensity of emotional expression, limited thought and speech productivity, social withdrawal, and reduced initiation of goal-directed behaviour. These negative components are typically characterised as affective flattening, alogia, diminished drive, anhedonia and avolition. Furthermore, schizophrenia is associated with cognitive impairment, disorganised speech and behaviour, as well as poor attention. The primary advance in pharmacological treatment of schizophrenia was in 1952 with the introduction of dopamine antagonist antipsychotic drugs.

Paradigm shift in schizophrenia research: from single-disease entity to the paradigm of multiple domains

A century of work has been based on designs that conceptualise schizophrenia as a single disease entity, despite recognition that schizophrenia must have scientific status of a syndrome in the absence of proof of a single disease process (Carpenter et al., 1999). The implications are profound. Research based on the presumption that a single disease is present has produced weak findings that frequently fail confirmation in replication studies. The heterogeneity of patients receiving this diagnosis is substantial. Causal and neuropathological findings valid for some patients will not be found in others. Illness manifestations vary substantially between patients, and symptomatic components of illness are only weakly related to each other within individuals.

READ MORE @ EUREKALERT

SSRI Use May Correlate With Lower Bone Mineral Density in Middle-Aged Women: Presented at ASBMR

A study presented at the 31st Annual Meeting of the American Society for Bone and Mineral Research (ASBMR) found that use of some antidepressants may have a correlation with reduced bone mineral density (BMD) in women.

While data have been circulated since the late 1990s associating the use of selective serotonin reuptake inhibitors (SSRIs) with an increased risk of hip fractures, the studies have been in elderly women.

"They were based on database studies and were not able to control for important variables such as bone density and other health conditions," said Susan Diem, MD, University of Minnesota, Minneapolis, Minnesota, on September 12. "Basic science data in the last few years have also found that serotonin transcriptors may exist on bone cells. SSRIs, which block serotonin transcription, might then have an effect on bone density."
READ MORE @ DOCTOR'S GUIDE

GlaxoSmithKline to Defend Paxil in Birth-Defect Case (Update1)

GlaxoSmithKline Plc, the world’s second-biggest drugmaker, begins a trial in Philadelphia next week in what may be a test case for more than 600 lawsuits over claims its antidepressant drug Paxil causes birth defects.

Patients and their parents claim internal company documents produced for trial show Glaxo failed to warn about the risks of Paxil until forced to do so in 2005 by the U.S. Food and Drug Administration. In a trial set for Sept. 14, Michelle David blames the drug for causing life-threatening heart defects in her son Lyam Kilker, 3.

The London-based company faces two more such trials a month from October through January in state court in Philadelphia. The first group will show both sides how the rest of the lawsuits may fare, said David Logan, dean and professor of law at Roger Williams University in Bristol, Rhode Island.

“These cases are sort of like the canary in the coal mine,” Logan said in a phone interview. “The early cases set the parameters for any global settlement negotiations.”

Paxil, approved by the FDA in 1992, generated about $942 million in sales last year, 2.1 percent of the total for the company. Glaxo has settled other Paxil-related cases, including a suit brought by the New York Attorney General’s office accusing the company of withholding safety data about the antidepressant.

READ MORE @ BLOOMBERG

Ghost authors remain a chronic problem

Journal articles often list a long string of putative authors. I once counted 47 on a physics paper. But where journal articles in the natural sciences often appear overly conscientious about acknowledging all contributors, the opposite has become a nagging problem in biomedicine. Here, not all authors on a research project – or even, necessarily, the most important ones – may be identified as a contributor.

The existence of these ghost authors, as they’re called, evoked frustration and anger yesterday in a large share of the 400 journal editors and clinical research scientists taking part in a quadrennial international workshop on peer review and biomedical publication. This year’s venue: Vancouver, British Columbia.

The concern, speakers complained, is that ghost writers can be little more than hired guns. The expectation is that they will describe research findings in ways that aid their benefactors – drug or biomedical device companies that wish to avoid the appearance of directly influencing a clinical trial’s interpretation.

Often aiding and abetting the situation is another group of poseurs known as honorary authors. Their names show up on papers – despite their having done nothing – to lend credibility to research, to reward a friend of someone connected with the study, or to help hide the contributions of a ghost.

READ MORE @ SCIENCE NEWS

Children with emotional difficulties at higher risk for adult obesity

Previous research has shown that low self-esteem and emotional problems are found in people who are overweight or obese– but not which influences which. Research published today in the open access journal BMC Medicine, sheds light on this issue showing that children with emotional difficulties are at higher risk for obesity in adult life.

Andrew Ternouth, David Collier and Barbara Maughan from the MRC Social, Genetic and Developmental Psychiatry Centre at the Institute of Psychiatry, King's College London, studied data from around 6,500 members of the 1970 British Birth Cohort Study who, as 10 year-olds, had been assessed for emotional problems, self-perceptions and BMI, and who reported on their BMI again at age 30. The researchers found that children with a lower self-esteem, those who felt less in control of their lives and those who worried often were more likely to gain weight over the next 20 years. They also found that girls were slightly more affected by these factors than boys.

READ MORE @ EUREKALERT

Depression After ACS Worsens Outcomes

Persistent depression after acute coronary syndrome continues to be a risk factor for early death for up to seven years, researchers said.

With a median of 6.7 years of follow-up, patients who encountered major depression after acute coronary syndrome -- and whose depression did not improve with treatment -- had a hazard ratio for death of 2.39 (95% CI 1.50 to 3.81) compared with those showing substantial improvement, according to Alexander Glassman, MD, of Columbia University, and colleagues.

The study involved patients in the randomized SADHART trial, which involved treatment with , sertraline (Zoloft) or placebo. Those who took their medications on schedule were more likely to show improvement in depression scores, the researchers wrote in the September issue of Archives of General Psychiatry.

Hence, they said, "physicians need to aggressively treat depression and be diligent in promoting adherence to guideline cardiovascular drug therapy."

The SADHART study (Sertraline Antidepressant Heart Attack Randomized Trial) began in 2000 with 369 patients hospitalized for acute coronary syndrome who were found to have major depression on screening.

READ MORE @ MEDPAGE TODAY

Brain Defect Implicated In Early Schizophrenia

In the first functional magnetic resonance imaging (fMRI) study of its kind, neurologists and psychiatrists at Columbia University have identified an area of the brain involved in the earliest stages of schizophrenia and related psychotic disorders.

Activity in this specific region of the hippocampus may help predict the onset of the disease, offering opportunities for earlier diagnosis and for the development of drugs for schizophrenia prevention.

Details of the findings were published in the September 7, 2009, issue of Archives of General Psychiatry.

In the study, the researchers scanned the brains of 18 high-risk individuals with "prodromal" symptoms, and followed them for two years. Of those individuals who went on to develop first-episode psychotic disorders such as schizophrenia, 70 percent had unusually high activity in this region of the hippocampus, known as the CA1 subfield.

SCIENCE DAILY

3 Genetic Variants Are Found to Be Linked to Alzheimer’s

Two teams of European scientists say they have discovered new genetic variants associated with Alzheimer’s disease. The variants account for about 20 percent of the genetic risk of the disease, and may lead to a better understanding of its biology, the scientists say.

One of the teams, led by Julie Williams of Cardiff University in Wales, scanned the genomes of about 19,000 patients, the largest study so far conducted on Alzheimer’s, and turned up two variants that have a statistically significant association with the disease. A second study, led by Philippe Amouyel of the University of Lille in France, also found two variants, one of which is the same as detected by the Cardiff team.

The fact that two studies could agree on at least one gene is an advance. More than 550 genes have been proposed in various small-scale studies as the cause of Alzheimer’s, but all have failed the test of replication by others, Dr. Amouyel said.

READ MORE @ NY TIMES

Depressed Teens Continue to Suffer Those with mild depression more likely to suffer major episode later, researchers say

Mildly depressed teenagers
are more likely to have major depression, anxiety disorders and eating disorders as adults, a new study suggests.

In 1983, researchers interviewed 755 teenagers who were about age 16 about mood, anxiety and eating disorders, disruptive behaviors and substance abuse.

About 8 percent were found to have minor depression, defined as feeling down, losing interest in normal activities, and having insomnia or difficulty concentrating for two weeks or more. The symptoms
of minor depression are similar to, but less severe, than those of a major depressive episode.

Researchers followed up with the teens when they were in their early 20s and in their early 30s, and found that teenagers who had had minor depression were significantly more likely to have major depression in adulthood.

READ MORE @ U.S. NEWS & WORLD REPORT

More drug firms doing follow-ups than thought--FDA

More pharmaceutical companies have completed studies required by U.S. health regulators after their products were allowed on the market than previously thought, according to an analysis released on Thursday.

But the study found that FDA database errors had obscured the issue, and critics said the post-approval studies, even when completed, still did not necessarily provide useful long-term information about the safety and effectiveness of the drugs.

Often, the Food and Drug Administration approves drugs and devices for sale on condition that companies keep studying the products for possible additional side effects or other issues.

For years, critics lamented such approvals because the FDA could only request more studies, but could not order them. The critics say companies had little incentive to do the studies once they won approval.

A 2007 law gave the agency more power to require the follow-up studies and ordered the analysis, which found more drug companies than previously thought had completed their studies. Results of the audit by Booz Allen Hamilton Inc were given to the FDA.

"Most companies are doing these studies and they are submitting the reports," said Dr. John Jenkins, director of the FDA's Office of New Drugs.

READ MORE @ REUTERS

Pfizer Pays $2.3 Billion to Settle Marketing Case

The pharmaceutical giant Pfizer agreed to pay $2.3 billion to settle civil and criminal allegations that it had illegally marketed its painkiller Bextra, which has been withdrawn.

It was the largest health care fraud settlement and the largest criminal fine of any kind ever.

Although the investigation began and largely ended during the Bush administration, top Obama administration officials held a news conference on Wednesday to celebrate the settlement, thank each other for resolving it and promise more crackdowns on health fraud.

“It’s another step in the administration’s ongoing effort to prosecute any individual or organization that tries to rip off health care consumers and the federal government,” said Kathleen Sebelius, secretary of health and human services.

Republicans and Democrats on Capitol Hill have accused the Obama administration of failing to crack down adequately on health care fraud, arguing that huge savings in government health programs could be found with better enforcement. The settlement had been expected. Pfizer, which is acquiring a rival, Wyeth, reported in January that it had taken a $2.3 billion charge to resolve claims involving Bextra and other drugs. It was Pfizer’s fourth settlement over illegal marketing activities since 2002.

READ MORE @ NY TIMES

Pills and America's pursuit of happiness

Antidepressant use has soared during the recession but reaching for the pill bottle goes back decades.

Of all the bitter pills Americans are swallowing nowadays, from joblessness to home foreclosures to runaway national debt, it might come as no surprise that a pill of another sort is flying off the shelves at a recession-defying pace – the antidepressant.

It's an easy jump to conclude that hard times are turning the country comfortably numb, as the Washington Post suggested in a weekend report on the sales of the drug Cymbalta, up 14 per cent since the summer of 2008 and now among America's most popular happy pills.

Drill deeper and you will find that the U.S., though far and away a world leader with its $10-billion-a-year antidepressant habit, is not alone.

Over the summer, British politicians fretted over the impact of recession on mental health amid data showing a spike of 2.1 million antidepressant prescriptions last year, when the downturn took its first precipitous dive.

Same in India, where pharmaceutical firms reported a 20 per cent expansion of the antidepressant market in the year ending December 2008. And in New Zealand, where the global plunge was linked to reports of a near doubling in antidepressant prescriptions between 2002 and 2008.

But drill down deeper still and the story behind the flurry of cause-and-effect headlines is far more nuanced.

While many researchers acknowledge there is likely an uptick in med sales as a consequence of the poor economy, most say it is driven as much or more by trends decades in the making.

READ MORE @ TORONTO STAR

Depressed teens 'face adult risk'

Teenagers who have minor depression are at a higher risk of mental health problems later in life, a study says.

Psychiatrists at Columbia University and the New York State Psychiatric Institute spoke to 750 people.

Anxiety, severe depression and eating disorders were all far more common in 20 and 30-year-olds who had had minor depression as adolescents, they found.

The British Journal of Psychiatry report said further research was needed to unpick the reasons for the link.

UK charities said specialist services for young people were vital.

The study was based on interviews with 750 14 to 16-year-olds who were then assessed again as adults.

READ MORE @ BBC NEWS

Generic versions of biologic medications are coming Companies most likely to produce biogenerics

The days of market exclusivity could soon come to an end for the biotech industry if Congress moves forward with plans to finally allow generic biologics on the U.S. market.

Because of their eye-popping price tags, pressure to rein in the cost of biologics has been mounting on Capitol Hill for some time. A process for approving generic versions of traditional chemical medications has been in place for more than a decade, but Congress has yet to establish a similar legal pathway for biologics.

But all that could change in the next few months. Currently, almost all of the leading healthcare reform bills circulating on the Hill call for allowing the Food and Drug Administration to establish an approval process for generic biologics, also known as biogenerics or biosimilars.

Unlike traditional drugs, which are comprised of chemicals, biologics use living cells to treat diseases and disorders. The drug category includes some of the most popular therapies on the market: Cancer treatments such as Roche's /quotes/comstock/11i!rhhby (RHHB.Y 39.12, -0.72, -1.81%) Avastin and Herceptin; rheumatoid arthritis drugs such as Amgen Inc.'s /quotes/comstock/15*!amgn/quotes/nls/amgn (AMGN 58.98, -0.80, -1.34%) and Wyeth's /quotes/comstock/13*!wye/quotes/nls/wye (WYE 47.79, -0.06, -0.13%) Enbrel, Johnson & Johnson's /quotes/comstock/13*!jnj/quotes/nls/jnj (JNJ 59.94, -0.50, -0.83%) and Schering-Plough Corp.'s /quotes/comstock/13*!sgp/quotes/nls/sgp (SGP 27.79, -0.39, -1.38%) Remicade, and Abbott Laboratories' /quotes/comstock/13*!abt/quotes/nls/abt (ABT 45.12, -0.11, -0.24%) Humira; and multiple sclerosis therapies such as Biogen Idec's /quotes/comstock/15*!biib/quotes/nls/biib (BIIB 49.24, -0.96, -1.91%) Avonex.

READ MORE @ MARKET WATCH

Antidepressants Vary More in Side Effects, Not Efficacy

Summary

[SIDE EFFECTS] The main differences among the newer antidepressants are side effects and drug interactions. See the Commentary for a drug-by-drug list of these key differences. [PCP's] This review comes from a group of primary care docs, which is important because most depression is treated by PCPs. [FOLLOW-UP] It emphasizes the need for follow-up 1-2 weeks after initial prescription, which is KEY to improving adherence and addressing new side effects.

READ MORE @ GERSON LEHMAN GROUP

Depression and The Recession: Cymbalta Sales Are on the Rise

During a downturn, we tend to seek the "bright spots" -- sectors or products that are doing well when all the rest are struggling. For example, there were plenty of reports over the past year about retail items -- lipstick, chocolate, and macaroni and cheese -- that were bucking downward trends and selling well during the slump. While these stories were cautiously upbeat, news of an uptick in antidepressant sales despite -- or perhaps because of -- the recession was just plain depressing.

Helplessness, pessimism and persistent sadness -- the main symptoms of depression -- didn't seem to abate as the economy crumbled. About 164 million antidepressant prescriptions were written in 2008, 4 million more than in 2007, according to IMS Health, a health-care information and consulting company.

Antidepressants were the third most prescribed type of drug in 2008, hitting $9.6 billion in sales, up from $9.4 billion the year before. Last month, Eli Lilly reported that second-quarter sales for Cymbalta -- which is on the verge of surpassing Effexor as the nation's best-selling antidepressant -- increased 14 percent over the past year. Our national reliance on these drugs is a stubborn trend. A study published in the August issue of Archives of General Psychiatry found that from 1996 to 2005, antidepressant use in the United States doubled.

READ MORE @ WASHINGTON POST