Depression - the facts and the fables

If there's one thing I love, it's academics who take on the work of investigative journalism, because they are dogged. This has been a bad week for the SSRI antidepressants. First there's the stuff you already know: bad data got buried. In a cracking new analysis of the "publication bias" in the literature, a group of academics this week published a paper in the New England Journal of Medicine which listed all the trials on SSRIs that had ever been formally registered with the Food and Drug Administration, and then went to look for the same trials in the academic literature.

Thirty-seven studies were assessed by the FDA as positive and, with one exception, every single one of those positive trials got properly written up and published. Meanwhile, 22 studies that had negative or iffy results were simply not published at all, and 11 were written up and published in a way that described them as having a positive outcome.

You're a sophisticated reader, so you understand this doesn't mean that they're necessarily rubbish drugs, but you also understand that this is dodgy behaviour, all the same.

That's the easy one.

READ MORE @ THE GUARDIAN

FDA fast-tracks first cocaine, meth addiction fighter

Deerfield-based Ovation Pharmaceuticals said Tuesday its drug vigabatrin, being developed to treat cocaine and methamphetamine dependence, has landed “fast track” designation from U.S. regulators potentially speeding up the process for market approval.

The drug would be the first approved by the U.S. Food and Drug Administration for treatment of the addictions.

The anticonvulsant drug, to be marketed under the brand name Sabril, is believed to block the craving and euphoria associated with cocaine and meth use. It is thought to work by increasing brain levels of so-called gamma-aminobutyric acid, a transmitter that inhibits certain activity in the brain.

Data from animal testing and two small-scale early-stage studies in people with chronic cocaine and meth addiction have found that when given Sabril, cocaine and meth users no longer have a craving for the drugs, and if the drugs are taken, the users have no euphoria related to taking them, executives have said.

Ovation is collaborating with the National Institute on Drug Abuse on Phase II studies to evaluate the safety of the drug. Phase III trials are expected to be launched by the end of next year.

READ MORE @ CHICAGO SUN-TIMES

Genetic changes key in antidepressant drugs: study

Changes in a gene that protects the brain from foreign substances may affect whether commonly used antidepressants work -- and a simple test could help doctors prescribe the right drug, researchers said on Wednesday.

The findings could also help doctors adjust doses to make the drugs more effective while cutting down on harmful side effects, said Florian Holsboer, director of the Max Planck Institute for Psychiatry in Munich, who led the study.

"This is the first step into personalized antidepressant treatment according to genetic makeup," Holsboer said. "The gene test can help the clinician when he makes a choice for the antidepressant he gives to the patient."

Depression is a leading cause of suicide and affects about 121 million people worldwide, according to the World Health Organization.

READ MORE @ REUTERS

F.D.A. Requiring Suicide Studies in Drug Trials

After decades of inattention to the possible psychiatric side effects of experimental medicines, the Food and Drug Administration is now requiring drug makers to study closely whether patients become suicidal during clinical trials.

The new rules represent one of the most profound changes of the past 16 years to regulations governing drug development. But since the F.D.A.’s oversight of experimental medicines is done in secret, the agency’s shift has not been announced publicly.

The drug industry, however, is keenly aware of the change. Makers of drugs to treat obesity, urinary incontinence, epilepsy, smoking cessation, depression and many other conditions are being asked for the first time by the drug agency to put a comprehensive suicide assessment into their clinical trials.

READ MORE @ NY TIMES

Jury Trials In 2008 Expected To Expose SSRI Maker's Dirty Secrets

Jury Trials In 2008 Expected To Expose SSRI Maker's Dirty Secrets

The blockbuster sales figures for the new generation of selective serotonin reuptake inhibitor antidepressants (SSRI's), which have resulted from their promotion for so many unapproved uses, represents the most profitable off-label marketing coup in the history of modern medicine. Sales total about $21 billion a year, according to IMS Health.

However, in the end these drugs will probably also hold the title for the most lawsuits filed against drug companies for overstating their benefits while concealing their serious side effects from as far back as 20 years ago.

The SSRI's include Prozac by Eli Lilly; Paxil marketed by GlaxoSmithKline, Zoloft by Pfizer, and Celexa and Lexapro from Forest Laboratories. Cymbalta by Eli Lilly and Effexor by Wyeth are often called SSRI's, but they are actually serotonin norepinephrine reuptake inhibitors (SNRI's). Wellbutrin sold by Glaxo is an inhibitor of the neuronal uptake of norepinephrine and dopamine. Several of these antidepressants now have generic counterparts.

READ MORE @ OPEDNEWS

Antidepressants behind 52 percent of all suicides among women

Incredible data have just been revealed that antidepressant drugs were behind 52 percent of all suicides among women (18-84) in Sweden (2006)

This is not data from a limited study; it instead concerns information on a national level for ALL suicides (18-84 years) for 2006. The information is unique; registries now exist in Sweden making it possible for the National Board of Health and Welfare to see how many of the suicides were preceded by psychiatric drug treatment.

Among a total number of 377 women who committed suicide, 197 (52%) had filled a prescription for antidepressants within 180 days before their death. And 29 women (8%) had filled a prescription for neuroleptics ("antipsychotics") ONLY within 180 days before the suicide.

This means that 229 women - 60% - of those who committed suicide (18-84) in Sweden (2006) had filled a prescription for antidepressant drugs OR neuroleptics within 180 days before their suicide.

Neuroleptics were involved in total in 97 (26%) of the suicides among women, (68 women, 18%, got BOTH antidepressants and neuroleptics). NOT included in these figures is the percentage of women who got other forms of psychiatric drugs, like benzodiazepines.

The data are revealed just after the news broke that pharmaceutical companies have systematically hidden negative and exaggerated positive results in their clinical trials of antidepressants (see article Antidepressant Studies Unpublished in NYT), thus misleading patients and doctors for many years.

READ MORE @ TRANS WORLD NEWS

Height link to suicide attempts

Men are less likely to attempt suicide if they are tall, research has shown.

A study in the Journal of Epidemiology and Community Health examined the suicide and death figures for 320,000 Swedish men born between 1973 and 1980.

It found that short babies - those less than 47cm in length at birth - were more likely to attempt suicide as adults, regardless of their eventual height.

Short birth length more than doubled the risk of violent suicide, defined as the use of guns or knives, jumping from a height or in front of vehicles, or drowning.

But short men who were born a normal length were also affected.

The study found they were 56% more likely to take their own lives than tall men.

The authors of the study suggested the brain chemical serotonin, which is crucial to brain development, could be the reason for their findings.

Low serotonin levels can trigger impulsive, aggressive and suicidal behaviour, and can be caused by premature birth and other factors affecting growth in the womb.

READ MORE @ THE PRESS ASSOCIATION

Should Bipolar Medication Be Halted During Pregnancy?

When faced with pregnant women who have bipolar disorder, clinicians are urged to balance carefully the potential harm of medication to the fetus and the high risk of recurrent mood episodes in the mother.

Pregnant women with bipolar disorder and their physicians face a dilemma: stay on mood-stabilizing medications, which carry risks of causing birth defects, or discontinue the medications and brace for the possibility of relapse.

The possibility of relapse due to interrupted pharmacotherapy has been quantified in a study published in the December 2007 American Journal of Psychiatry, which warns that pregnant women with bipolar disorder who discontinue mood stabilizers are much more likely to suffer the return of their illness than those who continue taking the medications.

READ MORE @ PSYCHIATRIC NEWS

Some Medications Can Be Difficult, Even Dangerous, To Stop

Savvy patients have learned that it is essential to ask physicians and pharmacists about side effects before they take any medicine. Drugs can cause reactions that range from mild discomfort to life-threatening complications.

Even a thoughtful consumer may forget another crucial question: What will happen when I stop this medication? Many drugs can cause trouble if they are stopped abruptly.

The patient information on the back of an ad for the antidepressant Effexor XR has a heading, "What happens when I stop using Effexor XR?" When people stop suddenly, they may experience symptoms such as agitation, anxiety, confusion, diarrhea, dizziness, dry mouth, muscle twitching, headaches, insomnia, loss of appetite, nausea, nervousness, nightmares, poor coordination, seizures, sensory disturbances (like electric-shock sensations), sleepiness, sweating, tinnitus, tremor, unpleasant mood or vomiting.

That's hardly a pleasant prospect. We wonder if people review that list before they begin taking this drug.

Effexor XR is not the only medicine that can cause symptoms if it is stopped abruptly. Other antidepressants, such as Paxil or Zoloft, may cause similar problems.

READ MORE @ HARTFORD COURANT

Facing lawsuit, state revisited prescription drug data law

A new Vermont law restricting the drug industry's use of data on doctors' drug prescribing habits is facing a federal lawsuit and a new round of scrutiny.
more stories like this

The law, which was amended in the waning days of last year's legislative session after a federal court struck down a similar measure in New Hampshire, contains several provisions aimed at slowing cost increases for prescription drugs.

One target of the measure was companies that gather information on which drugs doctors prescribe most often and then sell that information to pharmaceutical companies. The information allows the drug companies to develop sophisticated sales pitches, called "detailing," to entice doctors to switch to their medications, said Julie Brill, an assistant attorney general who worked on the legislation.

Brill called the so-called "data.m.ining" restrictions "one piece of a larger effort by the state to ensure that marketing that goes on with respect to pharmaceutical products is appropriate and ... also to protect the privacy concerns prescribers have."

READ MORE @ BOSTON GLOBE

Antidepressants don't work as well as reported, study says

New England Journal of Medicine reports that 88 per cent of clinical trials that showed the drugs didn't work either weren't published in medical journals or were presented as positive findings

Antidepressants are far less effective than doctors have been led to believe, a new study has found.

That's because 88 per cent of clinical trials that showed the drugs didn't work either weren't published in medical journals or were presented as positive findings, says the study in the New England Journal of Medicine.

It provides the first hard data on a practice known as selective reporting, in which the good news about a drug is made public but the bad news isn't. Ethicists say it gives doctors and patients too rosy a picture. Clinicians rely on the medical literature to learn about new drugs and to help them assess whether it is worth prescribing a medication, given the risk of side effects.

The researchers examined the studies that drug companies submitted to the Food and Drug Administration in the United States when they were seeking regulatory approval for 12 antidepressants. The drugs were all approved between 1981 and 2004, and are now widely prescribed. (Canada has its own drug approvals process, which relies on essentially the same information drug companies give the FDA.)

READ MORE @ GLOBE AND MAIL

On Parenting: Getting a Doctor to Face Behavioral Concerns

Pediatricians may not look after kids' mental health—unless parents lend a hand

When parents are worried about a child being depressed or having an eating disorder or a problem with drugs or drinking, the family pediatrician is the natural place to turn for help. But families might not get the help they need. Doctors, it turns out, are often reluctant to tackle children's mental and behavioral problems.

That's the sobering news from a study that offers clues as to why so many families struggle to get treatment for their troubled children. Fortunately, it also offers insight into how parents can work the system to get their children the help they need.

Mental-health care may sound like a frill compared with, say, treating asthma or strep throat. Yet mental-health problems are nearly twice as common as asthma, with at least 11 percent of children having a mental or behavioral disorder that significantly impairs their life. Given that, you'd think that pediatricians would be all over the mental-health issue.

READ MORE @ US NEWS & WORLD REPORT

Guidelines To Improve Care Of Three Symptoms At End Of Life

The American College of Physicians (ACP) has issued new guidelines to improve palliative care at the end of life (EOL).

The guidelines say that clinicians should regularly assess people with serious illness at the end of life for symptoms of pain, shortness of breath, and depression; that they should use proven therapies to treat these conditions; and should ensure that advance care planning occurs for all patients with serious illness.

"Many Americans will face a serious illness at the end of life and their families will be involved in their care," said Amir Qaseem, MD, PhD, MHA, Senior Medical Associate in the Clinical Programs and Quality of Care Department of the Medical Education and Publishing Division at ACP. "We wanted to pull together best available evidence on improving care that relieves or soothes symptoms at the end of life. Evidence review showed that the three most common symptoms were pain, difficult breathing and depression, so our guidelines address these."

READ MORE @ SCIENCE DAILY

Review of Adverse Effect Profile, Safety, and Dosing of Antidepressants

n 2002, 8.5% of the US population purchased at least one prescription antidepressant.1 Given this relatively high rate of antidepressant use, best practices should be followed in choosing the correct medication and dosing, to avoid adverse events or ineffective treatment. Two of the major classes of antidepressants that are more commonly prescribed are the selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressants (TCAs). The SSRIs are generally the antidepressants of first choice. They are relatively safe and effective. The Cochrane Collaboration reviewed 32 well-conducted trials and found SSRIs to be just as effective as TCAs with fewer adverse effects in the elderly population.2 In the inpatient population, TCAs appear to be slightly more effective than SSRIs, but TCAs were noted to have decreased tolerability.3 Given the popularity and tolerability of SSRIs, this review focuses mainly on this group of antidepressants and also touches on some of the newer unique antidepressants.

READ MORE @ ABKHAZIA

Doctors commonly enlist the power of placebos

Doctors prescribe placebos more often than patients might imagine.

A survey of Chicago-area physicians found that 45 per cent report they have given a patient a placebo at least once, according to a study published in this month's Journal of General Internal Medicine.

Past surveys of Israeli and Danish doctors revealed that 60 per cent and 85 per cent, respectively, admit they've relied on the "placebo effect" to heal patients.

So, should patients worry about their doctors shamming them?

Maybe not. Though prescribing dummy pills is viewed as ethically shady, the placebo effect can work. Brain-scan research indicates that placebos trigger pain-relieving endorphins in the brain. Indeed, anyone who has ever felt better after taking cough syrup may have enjoyed the placebo effect - some studies suggest that sugar water is just as good at healing sore throats. Belief in medicine can contribute heavily to its success.

Doctors turn to placebos for a variety of reasons, according to the Chicago study, including to calm the patient, as a last resort when nothing else works, or simply to get a patient to stop complaining.

READ MORE @ GLOBE AND MAIL

The Politics Of Depression

There was a fascinating exchange of letters in this month's American Journal of Psychiatry concerning just how much depression doctors should accept in their patients and the implications of such decisions. What prompted the initial letter was the federally-funded STAR-D trial, which showed that current depression treatments--including some psychotherapies--are no where near as robust as doctors (and presumably patients) would like. What the trial showed, in short, was that various anti-depressants had anywhere from an 8 percent to 30 percent chance of success in remitting symptoms of depression.

That leaves a large subset of people who do not get relief using current therapies and that raises a host of practical issues for the mental health field. This situation affects millions of Americans.

READ MORE @ FURIOUS SEASONS

Metformin and Counseling Retard Drug-Induced Weight Gain in Schizophrenia

For patients with schizophrenia taking antipsychotics, metformin or lifestyle counseling, or both combined, helps steer clear of drug-induced weight gain and insulin resistance, found investigators here.

In a randomized 12-week trial of 128 adults with schizophrenia, age 18 to 49, who had gained more than 10% of their pre-antipsychotic weight, metformin alone was more effective than lifestyle intervention alone, found Jing-Ping Zhao, M.D., Ph.D., and colleagues at the Second Xiangya Hospital here.

But a combined approach produced the better results, the research team reported in the Jan. 9/16 issue of the Journal of the American Medical Association.

Participants taking antipsychotic medications were randomized to one of four groups: 12 weeks of placebo, 750 mg/day of metformin alone, 750 mg/day of metformin with lifestyle intervention, or lifestyle intervention alone.

The lifestyle interventions included counseling and dietary and exercise programs, the researchers reported. Caregivers reported participants' food intake and exercise levels, the authors said.

READ MORE @ MEDPAGE TODAY

Effect of antidepressant warnings moderate-US study

Warnings that antidepressants might increase the risk of suicidal behavior in youth curbed rapid growth of these drugs but did not eliminate access to them among young people as some had feared, U.S. researchers said on Monday.

They said that while antidepressants had been growing at an annualized rate of 36 percent before regulators made the warnings in 2003, that growth flattened out after the warnings were issued.

Doctors have assumed that a spike in teen suicide in 2004 reulted from a sharp fall in use of antidepressants among children and youth.

That was not the case, according to Dr. Mark Olfson of Columbia University Medical Center.

"When the warnings first appeared, there was a great deal of concern among psychiatrists and other mental health professionals that these warnings would result in a precipitous decline in antidepressant use by young people, and as a result, youth with depression would have less access to treatment," said Olfson, whose study appears in the Archives of General Psychiatry.

READ MORE @ REUTERS

New treatment mechanisms for schizophrenia

The field of schizophrenia research has come alive with many exciting new potential approaches to treatment. From the introduction of chlorpromazine to the current day, all treatments approved by the U.S. Food and Drug Administration have had, at their core, a single treatment mechanism, the blockade of the dopamine D2 receptor. The introduction of clozapine in the 1980’s suggested a potential that other brain targets might complement the blockade of dopamine D2 receptors to treat symptoms that failed to respond to the “typical” antipsychotics. We are now entering an age where new treatments are being rationally developed within the context of translational neuroscience, i.e., the steps whereby basic molecular neuroscience leads to fundamental new mechanisms that can be tested in animal and human laboratory-based research that, in turn, leads to tests of new medications in our clinics. The January 1st issue of Biological Psychiatry includes encouraging new research related to three new treatment approaches.

In the first study, Olszewski and colleagues tested a novel drug that inhibits the breakdown of the transmitter N-acetylaspartylglutamate (NAAG), which activates a receptor that reduces schizophrenia-like behaviors in some animal models. Their findings indicate that this drug is effective in an animal model of schizophrenia. Joseph H. Neale, Ph.D., lead author on this project, comments, “While treating patients with receptor agonists can be highly effective therapy, drugs that increase the action of the transmitter that activates the same receptor have traditionally been very effective with fewer side effects than chronic agonist treatment.” He adds, “These data support the conclusion that NAAG peptidase inhibitors represent a breakthrough in the discovery of a completely novel means of adjunct therapy for schizophrenia that is analogous to the use of SSRIs [selective serotonin reuptake inhibitors] for the treatment of depression."

READ MORE @ EUREKALERT

Genetic variant predicts antipsychotic response for schizophrenia patients by ethnicity

Schizophrenia is a developmental disorder with a large genetic component contributing to increased risk. Available antipsychotic medications treat some of the symptoms of schizophrenia, but are typically effective in only a subset of patients. Unfortunately, it is difficult to predict the effectiveness of a specific drug in any given individual with schizophrenia. John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, notes that “in this era of medicine, the selection of particular antipsychotic medications for particular patients with schizophrenia is more art than science. We have been seeking objective guides, perhaps biological tests, which would inform this process.” A new study published in the January 1st issue of Biological Psychiatry provides some interesting data to aid in that goal.

The authors report that differential effectiveness of antipsychotic treatment was predicted, in a subset of patients with schizophrenia, by variants of the gene encoding for the regulator of G-protein signaling 4 (RGS4), a protein that regulates the functional consequences of activating neurotransmitter receptors. Dr. Daniel Campbell, corresponding author for this article, explains these results: “By applying genetic analysis to the NIMH-funded Clinical Antipsychotic Trials of Intervention Effectiveness, we show that variants in a specific gene, RGS4, predict the effectiveness of different antipsychotic treatments. Our results also indicate that the predictive power of the RGS4 genetic variants differed between patients of self-reported African and European ancestry, and thus emphasize the importance of including multiple ethnic groups in a study.”

READ MORE @ EUREKALERT