Yourlawyer.com (Wellbutrin News)

Generic Wellbutrin Gets FDA Backing, Despite User Complaints

Fri, 18 Apr 2008 00:00:00 -0700

Despite complaints from patients, the US Food and Drug Administration (FDA) says a cheaper, generic version of GlaxoSmithKline PLC's Wellbutrin XL antidepressant is safe and effective. The FDA said it received 85 reports from patients who switched from Wellbutrin XL to either Teva Pharmaceutical Industries Ltd. or Impax Laboratories Inc.'s cheaper generic. Of these, 78 people said their depression returned once they stopped taking the name brand and began a generic. Others reported new or worsening side effects including headaches, fatigue, anxiety, and digestion issues.

"The question is whether the reported lack of efficacy and/or new onset side effects in these patients who switched suggest a problem with the generic product ... or have some other explanation," the FDA said. Agency scientists reviewed 300-milligram versions of the two drugs, which both use once-a-day formulations of the chemical bupropion. According to the FDA, half of the patients who resumed taking the name-brand drug said they improved. The FDA said it would continue to monitor the issue. The FDA does not subject generics to the same level of scrutiny as brand name drugs; therefore, there is concern that these problems do not reflect isolated incidents.

Meanwhile, previous studies comparing Teva’s generic Budeprion XL with Wellbutrin XL found that although the generic contained the same active ingredient as the brand name, it performed differently in lab tests. The consumer advocacy website ConsumerLab.com conducted an investigation following hundreds of complaints from former Wellbutrin XL users that Budeprion XL was not working as well. ConsumerLab.com found both versions contained the stated amount of the active ingredient bupropion; however, differences occurred when the drugs underwent “dissolution testings.” Both medications are time-released, meaning the active ingredient is released over a period of many hours. In Wellbutrin XL, tests showed that in two hours, about 8% of the bupropion was released; in the generic, 34% was released in the same period. Receiving a higher dose of brupropion up front could have caused the headaches, irritability and nausea so many generic users complained of. Worse, more serious problems, like a return of depression or suicidal thoughts, could be the result of less medication entering the patients’ bloodstreams later in the day.

Add all this to the FDA’s uneven inspection processes and issues with foreign-manufactured drug components. Drug imports increased in the past five years, but inspection funds dropped. While 3,250 non-US plants were subject to FDA inspections last year, it only conducted 1,445 in the last five years. It’s worse in China where the FDA averaged just 15 inspections in each of the last five years, despite that there are 714 plants shipping drug products to the US. If China's 17% annual growth rate for drug exports continues, they will produce about 25% of the world's pharmaceutical ingredients by 2010. "Millions of FDA-regulated products are imported into the country each year from foreign facilities that have never been inspected by FDA and, with current appropriations, never will be," according to the FDA Science Board's subcommittee on science and technology. The head of the FDA study group, in an interview, held out little hope the FDA is coming to grips with its challenges.

Published Antidepressant Studies Exaggerate Their Effectiveness

Thu, 17 Jan 2008 00:00:00 -0800

Antidepressants like Effexor, Zoloft, Wellbutrin and Paxil, may not be as effective in treating symptoms of depression as once thought. That’s because studies done on many popular antidepressants have been skewed in a way that exaggerates their effectiveness. In many cases, only research that casts antidepressants in a favorable light is published.   Meanwhile, studies with less-than-favorable results are often mothballed by the pharmaceutical companies that make antidepressants.

The overwhelming amount of published research on antidepressants show that these drugs are effective in treating depression and other psychological problems. But according to an article in the New England Journal of Medicine, these published studies don’t tell the whole story. According to a data review submitted to the Food & Drug Administration (FDA), the vast majority of unpublished antidepressant studies found the drugs to be less effective than those that made it into medical journals.

According to the New England Journal of Medicine, of 74 antidepressant studies reviewed, 38 were deemed favorable to antidepressants.   Of those favorable studies, all but one where published. Of the unfavorable studies, 22 of 36 where never published. Even more outrageous, of the 14 unfavorable studies that were published, at least 11 mischaracterized the results and presented a negative study as positive.

The antidepressant studies that the New England Journal of Medicine looked at involved some of the most popular drugs on the market. For example, in five clinical trials done on the Pfizer drug Zoloft, two published studies showed Zoloft appeared to work better than the placebo. But in three other Zoloft trials, the placebo did just as well at reducing indications of depression. Pfizer never published the three unfavorable studies, and the company discusses only the positive results in Zoloft's literature for doctors.

Even when studies where published, researchers found that drug companies found ways to manipulate them to make findings appear more favorable to an antidepressant than they really where. For example, sometimes drug makers ignore or downplay a negative finding for the "primary outcome" -- the main question the study was designed to answer -- and highlight a positive secondary outcome. In nine of the negative studies that were published, the authors simply omitted any mention of the primary outcome, the researchers said.

According to The Wall Street Journal, sales of antidepressants total about $21 billion a year. Considering this, it is understandable that drug makers would want to protect these sales.   But suppressing the results of unfavorable studies affects more than antidepressant sales. Doctors unaware of the unpublished data are making inappropriate antidepressant prescribing decisions that aren't in the best interest of their patients. Sales of antidepressants are so huge because doctors and patients have been given the wrong impression about their effectiveness. "There is a view that these drugs are effective all the time," Dr. Erick Turner, a lead researcher on the study, told the Wall Street Journal. "I would say they only work 40% to 50% of the time."

New Research Shows Generic Wellbutrin Many Not be as Effective as Brand Name Medication

Fri, 12 Oct 2007 00:00:00 -0700

A generic version of Wellbutrin might not treat depression as effectively as the name brand medication, and that could be putting patients at risk. A new study comparing Teva Pharmaceutical’s generic Budeprion XL with Wellbutrin XL found that although the generic antidepressant contained the same active ingredient as the brand name drug, it performed differently than Wellbutrin XL in lab tests. The new research raises serious questions about the way the Food & Drug Administration (FDA) approves all generic prescription drugs.

The investigation into Budeprion XL was conducted by the consumer advocacy website ConsumerLab.com, after the writers of a syndicated newspaper column reported receiving hundreds of complaints from former Wellbutrin XL users that Budeprion XL was not working as well. ConsumerLab.com performed lab analysis of the antidepressants, and found that both versions contained the stated amount of the active ingredient bupropion. But differences between Wellbutrin XL and Budeprion XL became apparent when the drugs were subjected to “dissolution testing”. Both Wellbutrin XL and Budeprion XL are time-released medications, meaning that the active ingredient is released into a patient’s system over a period of many hours. In the case of Wellbutrin XL, the tests showed that in two hours, only about 8% of the bupropion was released. But in the case of the generic Budeprion XL, 34% of its active ingredient had already been released in the same period. Four hours into the dissolution test, and Wellbutrin had only released 25% of its active ingredient, but for the generic drug, half of the bupropion was already released.

This could explain why some people who switch from Wellbutrin XL experience difficulties on Budeprion XL. Getting a higher dose of brupropion up front could have caused the headaches, irritability and nausea so many Budeprion XL users complained of. And even more serious problems, like a return of depression or suicidal thoughts, could be the result of less medication entering the patients’ bloodstreams later in the day.

As if the results of the Wellbutrin/Budeprion study aren’t disturbing enough, the ConsumerLab.com researchers warned that such problems could be typical of other generic drugs. That’s because the FDA does not subject these medications to the same level of scrutiny as name brand medications. For example, when a pharmaceutical company wants to bring a new brand name drug to market, the company must demonstrate its effectiveness and safety through extensive clinical trials. But to sell a generic version, a company is only required to provide the FDA with lab data and test results from 24 to 36 volunteer subjects that shows the drug works similarly to the name brand medicine. The ConsumerLab.com findings now have some doctors and consumer advocates wondering if the FDA’s approval standards for generic drugs are adequate.

Generic drugs are generally much less expensive than name brands. For example, a three month supply of Budeprion XL costs less than $60, while the same amount of Wellbutrin XL costs well over $200. As a result many insurance companies will only pay for a generic version of a drug if one is available, and the FDA has planned to speed up approvals for generics as way to help consumers deal with the high cost of prescription drugs. But as the ConsumerLab.com study demonstrates, not all drugs are equal. For that reason, anyone who switches from a brand name prescription medication to a generic version should report any new side effects or other issues to their doctors.

FDA Again Warns About Suicidal Thoughts and Behavior Among Young Adults on Antidepressants

Thu, 03 May 2007 00:00:00 -0700

The U.S. Food and Drug Administration (FDA) today issued new warnings about suicidal thoughts and behavior related to young adults taking antidepressants, and they have asked drug makers to update their label warnings appropriately.

The FDA uses the term “suicidality” to describe what they call suicidal thinking and behavior. The new “black-box” label warnings, the most strident type of warning, would reflect the increased risks of suicidality in young adults, ages 18 to 24, during the initial stages of treatment, which usually encompasses the first couple of months.

“Today’s actions represent FDA’s commitment to a high level of post-marketing evaluation of drug products,” said Steven Galson, director of the FDA’s Center for Drug Evaluation and Research. “Depression and other psychiatric disorders can have significant consequences if not appropriately treated. Antidepressant medications benefit many patients, but it is important that doctors and patients are aware of the risks.”

The updated warnings would, naturally, include several mitigating points as well. The new labels would stress the fact that the increased risk of suicidality has not been scientifically proven among patients older than 24, and also that patients older than 65 have actually been shown to have a decreased risk of suicidal thoughts and behavior when taking antidepressants. The warnings would also include language reminding consumers about the serious risks associated with untreated depression and other psychiatric disorders.

However, the FDA made it clear that the new warnings apply to “the entire category of antidepressants” and that available data “are not sufficient to exclude any single medication from the increased risk of suicidality.”

The FDA mandated similar labeling changes to antidepressants in 2005, but those warnings were specific to the suicidality risk in children and adolescents only. Since that time, the FDA has attempted to ascertain the risk of suicidality in adults taking antidepressants by conducting comprehensive reviews of 295 individual antidepressant trials that included more than 77,000 adult patients with major psychiatric disorders. Five months ago, the FDA’s Psychopharmacologic Drugs Advisory Committee recommended that the label warnings be updated to include young adults, but only now has the FDA taken any decisive action.

The drugs associated with the new label warnings are:
Anafranil (clomipramine)
Asendin (amoxapine)
Aventyl (nortriptyline)
Celexa (citalopram hydrobromide)
Cymbalta (duloxetine)
Desyrel (trazodone HCl)
Elavil (amitriptyline)
Effexor (venlafaxine HCl)
Emsam (selegiline)
Etrafon (perphenazine/amitriptyline)
fluvoxamine maleate
Lexapro (escitalopram hydrobromide)
Limbitrol (chlordiazepoxide/amitriptyline)
Ludiomil (maprotiline)
Marplan (isocarboxazid)
Nardil (phenelzine sulfate)
nefazodone HCl
Norpramin (desipramine HCl)
Pamelor (nortriptyline)
Parnate (tranylcypromine sulfate)
Paxil (paroxetine HCl)
Pexeva (paroxetine mesylate)
Prozac (fluoxetine HCl)
Remeron (mirtazapine)
Sarafem (fluoxetine HCl)
Seroquel (quetiapine)
Sinequan (doxepin)
Surmontil (trimipramine)
Symbyax (olanzapine/fluoxetine)
Tofranil (imipramine)
Tofranil-PM (imipramine pamoate)
Triavil (perphenazine/amitriptyline)
Vivactil (protriptyline)
Wellbutrin (bupropion HCl)
Zoloft (sertraline HCl)
Zyban (bupropion HCl)

FDA Proposes New Warnings About Suicidal Thinking, Behavior in Young Adults Who Take Antidepressant Medications

Wed, 02 May 2007 00:00:00 -0700

The U.S. Food and Drug Administration (FDA) today proposed that makers of all antidepressant medications update the existing black box warning on their products' labeling to include warnings about increased risks of suicidal thinking and behavior, known as suicidality, in young adults ages 18 to 24 during initial treatment (generally the first one to two months).

The proposed labeling changes also include language stating that scientific data did not show this increased risk in adults older than 24, and that adults ages 65 and older taking antidepressants have a decreased risk of suicidality. The proposed warning statements emphasize that depression and certain other serious psychiatric disorders are themselves the most important causes of suicide.

"Today's actions represent FDA's commitment to a high level of post-marketing evaluation of drug products," said Steven Galson, M.D., MPH, director of FDA's Center for Drug Evaluation and Research. "Depression and other psychiatric disorders can have significant consequences if not appropriately treated. Antidepressant medications benefit many patients, but it is important that doctors and patients are aware of the risks."

People currently prescribed antidepressant medications should not stop taking them. Those who have concerns should notify their health care providers.

The proposed labeling changes apply to the entire category of antidepressants. Results of individual placebo-controlled scientific studies are reasonably consistent in showing a slight increase in suicidality for patients taking antidepressants in early treatment for most of the medications. Available data are not sufficient to exclude any single medication from the increased risk of suicidality.

The proposed labeling update follows similar labeling changes made in 2005 that warned of a suicidality risk in children and adolescents who use antidepressants. At that time, FDA asked manufacturers to add a black box warning to the labeling of all antidepressants to describe this risk and to emphasize the need for appropriate monitoring and close observation, particularly for younger patients taking these medications. In addition, FDA directed manufacturers to develop Medication Guides, FDA-approved user-friendly information for patients, families and caregivers, that could help improve monitoring. Medication Guides are intended to be distributed at the pharmacy with each prescription or refill of a medication.

Also in 2005, FDA began a comprehensive review of 295 individual antidepressant trials that included over 77,000 adult patients with major depressive disorder (MDD) and other psychiatric disorders, to examine the risk of suicidality in adults who are prescribed antidepressants.

In December 2006, FDA's Psychopharmacologic Drugs Advisory Committee agreed that labeling changes were needed to inform health care professionals about the increased risk of suicidality in younger adults using antidepressants. Additionally, the committee noted product labeling needed to reflect the apparent beneficial effect of antidepressants in older adults and to remind health care professionals that the disorders themselves are the most important cause of suicidality.

FDA has been developing language to revise product labeling and update the Patient Medication Guides for these products. Manufacturers of antidepressants will now have 30 days to submit their revised product labels and revised Medication Guides to FDA for review.

Products involved in today's action include:

Anafranil (clomipramine)
Asendin (amoxapine)
Aventyl (nortriptyline)
Celexa (citalopram hydrobromide)
Cymbalta (duloxetine)
Desyrel (trazodone HCl)
Elavil (amitriptyline)
Effexor (venlafaxine HCl)
Emsam (selegiline)
Etrafon (perphenazine/amitriptyline)
fluvoxamine maleate
Lexapro (escitalopram hydrobromide)
Limbitrol (chlordiazepoxide/amitriptyline)
Ludiomil (maprotiline)
Marplan (isocarboxazid)
Nardil (phenelzine sulfate)
nefazodone HCl
Norpramin (desipramine HCl)
Pamelor (nortriptyline)
Parnate (tranylcypromine sulfate)
Paxil (paroxetine HCl)
Pexeva (paroxetine mesylate)
Prozac (fluoxetine HCl)
Remeron (mirtazapine)
Sarafem (fluoxetine HCl)
Seroquel (quetiapine)
Sinequan (doxepin)
Surmontil (trimipramine)
Symbyax (olanzapine/fluoxetine)
Tofranil (imipramine)
Tofranil-PM (imipramine pamoate)
Triavil (perphenazine/amitriptyline)
Vivactil (protriptyline)
Wellbutrin (bupropion HCl)
Zoloft (sertraline HCl)
Zyban (bupropion HCl)

FDA plans to expand antidepressant warning

Thu, 14 Dec 2006 00:00:00 -0800

A Food and Drug Administration federal panel Wednesday recommended the agency issue its strongest possible warning to alert patients and doctors that antidepressants can increase the risk of suicidal thoughts and behavior in young adults.

The panel called for placing the so-called black-box warning on product labels and in medication guides distributed to patients.

Following the vote, FDA officials said they intended to expand the warning to include young adults.

Since 2004, antidepressants have had a black-box warning about an increased risk of suicidal thoughts and behavior in children and adolescents.

The recommendation to extend that warning to patients in their late teens and 20s came after the FDA's review of 372 clinical trials. The review found the risks were related to age and the dangers seemed to disappear at age 25.

Still, some panel members said that 25 seemed like an arbitrary cutoff and that the risks for a 25-year-old were probably not much different from those for a 24-year-old.

"I am concerned that there is a false sense of security to some of these age brackets," said panel member Dr. Marcia J. Slattery, a University of Wisconsin psychiatrist.

She said all patients taking antidepressants should be monitored for signs of suicidal thoughts and behavior.

In the end, the panel decided to leave the age limit of the warning for the FDA to decide. Patients younger than 25 account for about 8% of all antidepressant prescriptions.

The panel's 6-2 vote came amid concerns the black box might discourage young adults who need help from using the drugs, which many doctors said were among the most effective treatments for depression.

Several panelists called for balancing the warning with a statement underscoring the necessity of treating depression.

"We are dealing with a very vulnerable population," said panel member Gail W. Griffith, a patient representative from Washington.

The FDA's review, which looked at 100,000 patients, found a small but significant risk of suicidal thoughts and behavior among 18- to 24-year-olds who took antidepressants. The agency said that four of 1,000 patients were at increased risk.

The FDA study found no increased risk for patients ages 25 to 30. The drugs seemed to protect against suicidal thoughts and behaviors after age 30 and particularly after age 65, the agency said.

The FDA had no explanation for the apparent age-related effects of antidepressant drugs.

Half of the patients studied took the drugs for depression, while the rest were testing the medicines for psychological disorders, such as anxiety, or behavior modification, including smoking cessation and obesity.

Across all the studies, eight people committed suicide, 134 attempted suicide and 528 thought about killing themselves or prepared to do so. The FDA said suicides were too infrequent to draw any association to the drugs.

The research focused on 11 commonly used antidepressants: selective serotonin reuptake inhibitors Celexa, Lexapro, Luvox, Paxil, Prozac and Zoloft; serotonin-norepinephrine reuptake inhibitors Cymbalta and Effexor; other antidepressants Remeron, Serzone and Wellbutrin.

The panel's decision applies to all antidepressants, including an older class known as tricyclics.

About 19 million people in the U.S. have depression and 16 million are treated with antidepressants, according to Mental Health American, an advocacy group.

The vote came after an emotional hearing in which family members pleaded for strong warnings on drugs that they believed had caused loved ones' suicides.

"We deserve to be told all the side effects," said Kim Witczak of Minneapolis, whose husband, Woody, 37, hanged himself in 2003 after being prescribed Zoloft for insomnia.

But members of medical associations argued against the black box, saying it could indirectly lead to an increase in suicides because doctors might be afraid to prescribe the drugs for people who need them.

Dr. Carolyn Robinowitz, president of the American Psychiatric Assn., said suicides among 10- to 14-year-olds rose 16% to 244 in 2004 as antidepressant prescribing fell in advance of the FDA warning about suicidal thoughts and behaviors in adolescents.

"The black box has had unintended consequences," she said. "Depression can be lethal."

Last year, prescriptions for antidepressants fell 13% among children and adolescents and 8% among adults under 25, according to the prescription-tracking firm Verispan.

Study shows pills raise suicide risk in young adults

Thu, 14 Dec 2006 00:00:00 -0800

Widely used antidepressants double the risk of suicidal behavior in young adults, from around three cases per thousand to seven cases per thousand, according to a federal analysis of hundreds of clinical trials. It marks the first time regulators have acknowledged that the drugs can trigger suicidal behavior among patients older than 18.

Officials at the Food and Drug Administration said Wednesday that the higher risk was found in patients between 18 and 25 and that the risk faded among older patients. The finding comes two years after the agency ordered a ''black box'' warning on the drug labels after the discovery of a heightened risk of suicidal behavior among children taking the pills.

After reviewing the latest data, an expert federal panel on Wednesday recommended that agency officials tell doctors and the public of the risk but also find a way to note that the risk declines with age, and that leaving depression untreated also is risky.

While the studies on the relationship between the drugs and suicide appear contradictory, the experts said one possibility is that the drugs may pose a risk early in treatment but have a protective effect in the long term.

The agency is leaning toward expanding its black box warning, said Thomas Laughren, director of FDA's division of psychiatric drug products. Officials said they will try to craft language that would urge clinicians to use the drugs carefully, not abandon them.

The new finding created a dilemma for the regulators. Even as it vindicated some of what critics of drugs such as Prozac, Paxil and Zoloft have said for years, the earlier official warnings about the drugs appear to have led to a drop in their use and there are troubling signs that this can lead to an increase in suicides.

After concerns were raised in the Netherlands about the suicide risk, there was a 22 percent drop from 2003 to 2005 in antidepressant prescriptions for patients younger than 18 and a 50 percent increase in suicides, said Robert Gibbons, a professor of psychiatry at the University of Illinois in Chicago. The number of suicides went from 34 to 51.

''What we are seeing is the early signs of an epidemic of suicide in children who are no longer being treated for their depression,'' Gibbons said in an interview. U.S. suicide data for 2005 is not yet available, but Gibbons said the FDA's black box warning had caused a similar decline in prescriptions among children here. He predicted dozens of additional suicides as a result and warned that any expansion of the black box would have a similar impact on adults.

Robert Temple, director of FDA's Office of Medical Policy, said regulators were in a bind. On the one hand, they need to tell physicians about the new results in order to warn them to monitor patients closely for suicidal behavior, but if that means doctors stop prescribing the drugs altogether, ''I don't know what you are supposed to do.''

FDA may expand antidepressant warning

Wed, 13 Dec 2006 00:00:00 -0800

Treatment with antidepressants increases the risk of suicidal thoughts and behavior in patients age 24 and younger, according to proposed changes to the drugs' labels unveiled Wednesday by federal health officials.

The proposed changes would expand a warning now on the labels that applies only to children and adolescents treated with the drugs.

The Food and Drug Administration put forth its plan to update the drug labels early Wednesday at the start of a meeting of outside advisers convened to discuss the proposal. The changes also would include a recommendation that patients of all ages be carefully monitored, especially when beginning antidepressant treatment.

Mental health experts are worried that additional warnings about the risk of suicides linked to antidepressants could curtail their use and ultimately do more harm than good.

The proposed changes come on the heels of an FDA review that found use of the drugs may increase the risk of suicidal thoughts and behavior among young adults ages 18 to 24.

But adding "black box" or other warnings to the drugs could scare away doctors, parents and patients, mental health experts caution. They warn that people with untreated depression about half of those who suffer from the disease face an estimated 15 percent greater likelihood of death by suicide.

"My concern is that by not simply promoting good standards of care and by putting on a black-box label, the FDA may unwittingly limit further access to care," said Dr. Carolyn Robinowitz, president-elect of the American Psychiatric Association.

However, use of antidepressants continues to grow, with nearly 190 million prescriptions dispensed in the United States last year, according to IMS Health, a health care information company. That suggests doctors have placed more weight on the long-term benefits of the drugs than on any short-term risks, Dr. Thomas Laughren, director of the FDA's division of psychiatry products, told panelists.

The FDA recently completed a mass review of 372 studies involving about 100,000 patients and 11 antidepressants, including Lexapro, Zoloft, Prozac and Paxil. When the results are analyzed by age, it becomes clear there is an elevated but short-term risk for suicidal thoughts and behavior among adults 18 to 24 that approaches that seen in children, the FDA said in documents released before Wednesday's meeting of its psychopharmacologic drugs advisory committee.

The FDA's analysis of the multiple studies suggests an age-related shift in the risk of suicidal thoughts and behavior associated with treatment with the drugs. For instance, antidepressants seem to protect against suicidal thoughts and behavior in adults 30 and older, with the effect most pronounced in patients over 65.

In May, GlaxoSmithKline and the FDA warned Paxil may raise the risk of suicidal behavior in young adults and changed the drug's label to reflect that risk.

Already Linked to Suicide, New Research Links SSRI Antidepressants with Violence

Mon, 11 Sep 2006 00:00:00 -0700

New research has linked antidepressants, known as selective serotonin reuptake inhibitors or SSRIs, with violent episodes. Researchers found people who took the antidepressant Paxil were twice as likely to have a violent or “hostility event” as those given a placebo. Controversy is nothing new to SSRIs, in 2004 the FDA required the warning labels on these drugs to contain language about suicide risks.

The researchers used data from Britain’s Committee on Safety of Medicines Expert Working Group, legal cases and e-mails from 1,374 patients in response to a British television program on the subject. They found that 60 out of 9,219 people who took Paxil or 0.65 percent, had “a hostility event,” compared to 20 of 6,455 given a placebo, or 0.31 percent. The research appeared online in the journal Public Library of Science-Medicine.

Popular SSRIs include: Celexa, Lexapro, Prozac, Paxil, Zoloft and Luvox. It is still not exactly known why SSRIs help treat depression. It is believed that neurotransmitters, including serotonin, are associated with depression. SSRIs seem to help symptoms of depression by blocking the reabsorption (reuptake) of serotonin by certain nerve cells in the brain. This leaves more serotonin available, which enhances neurotransmission and helps treat depression.

www.newsinferno.com

FDA Warns of Suicide Risk for Paxil

Fri, 12 May 2006 00:00:00 -0700

The antidepressant Paxil may raise the risk of suicidal behavior in young adults, GlaxoSmithKline and the
Food and Drug Administration warned Friday in a letter to doctors.

The warning letter was accompanied by changes to the labeling of both Paxil and Paxil CR, a controlled-release version of the drug, also called paroxetine.

A recent analysis of clinical trial data on nearly 15,000 patients treated with both Paxil and dummy pills revealed a higher frequency of suicidal behavior in young adults treated with the drug, according to the letter.

The FDA reported that there were 11 suicide attempts none resulting in death among the patients given Paxil in the trials. Just one of the dummy pill patients attempted suicide.

Given that small number, the results "should be interpreted with caution," the FDA said. Eight of the 11 attempts were made by patients between the ages of 18 and 30. All trial patients suffered from psychiatric disorders, including major depression.

A GlaxoSmithKline spokeswoman did not immediately return a message seeking comment. However, in the letter to doctors, Dr. John E. Kraus, the company's director of clinical development for clinical psychiatry in North America, said GlaxoSmithKline continues to believe the drug's benefits outweigh its risks.

The FDA stressed that all patients, especially young adults and those who are improving, should be carefully monitored when treated with Paxil.

In 2004, the FDA ordered strong warnings about the pediatric risk of suicidal tendencies put on antidepressant labels, and began analyzing whether adults face a similar risk.

All antidepressants now carry warnings on their labels cautioning patients and doctors of the risk of suicidal behavior.

Health Canada Issues Advisory Regarding Link between Newer Antidepressants and Life-Threatening Respiratory Condition

Sun, 12 Mar 2006 00:00:00 -0800

Health Canada has issued a strongly worded “Advisory” to women who are taking newer antidepressants known as Selective Serotonin Re-uptake Inhibitors (SSRIs) and who are pregnant or intend to become pregnant.

They are being advised to discuss the situation with their doctor due to potential life-threatening risks to their babies.
Equally important is the fact that patients taking SSRIs should not stop taking them without first consulting their doctors, as abrupt termination of these medications can cause them to experience serious side effects.

According to the advisory: “Generally, SSRI treatment should only be continued if the benefits to the individual patient are thought to outweigh the risks to the unborn child, while also considering the benefits and risks of switching to another treatment option or stopping treatment altogether.”

SSRIs and other newer antidepressants prescribed for the treatment of depression include the following drugs: Wellbutrin (bupropion), Celexa (citalopram), Cipralex (escitalopram), Prozac (fluoxetine), Luvox (fluvoxamine), Remeron (mirtazapine), Paxil (paroxetine), Zoloft (sertraline) and Effexor (venlafaxine), and Zyban (bupropion) for smoking cessation.

A recent study published in the New England Journal of Medicine suggests that “use of SSRIs during the second half of pregnancy may be associated with a serious condition called persistent pulmonary hypertension of the newborn.”

Newborns with this rare but life-threatening condition do not receive enough oxygen in the blood and require intensive-care treatment to survive.

According to the study, babies born with this condition were six times more likely than healthy babies to have been exposed to SSRIs. This information is still considered to be preliminary.

Numerous reports in Canada and abroad have already indicated that some children exposed to SSRIs and other newer antidepressants during pregnancy may develop serious complications at birth.

“An increase in the overall risk of major birth defects has also been associated with SSRI use.”

Health Canada intends to “vigilantly” monitor the situation and issue additional advisories “if new concerns arise.”

Health Canada advisories on other SSRI-related complications in newborns are available on the Health Canada website (see August 9, 2004, October 6, 2005 and December 22, 2005).

Health Canada stresses that: “Managing the adverse reactions of marketed health products depends on the active participation of both healthcare professionals and consumers in reporting these reactions. The spontaneous reporting of adverse reactions generally underestimates the risks associated with the use of marketed health products.”

To report a suspected adverse reaction to SSRIs or other newer antidepressants, please contact the Canadian Adverse Drug Reaction Monitoring Program (CADRMP) of Health Canada by one of the following methods:

Telephone: 866-234-2345; Facsimile: 866-678-6789; CADRMP, Marketed Health Products Directorate, Health Protection Building, Tunney’s Pasture, AL 0701C; Email: cadrmp@hc-sc.gc.ca

Consumers requiring more information about this advisory can contact the Health Canada public inquiries line at (613) 957-2991, or toll free at 1-866-225-0709.

SSRI Antidepressants Linked To Serious Lung Disorder in Newborns

Fri, 10 Mar 2006 00:00:00 -0800

Health Canada is advising women who are taking antidepressants known as Selective Serotonin Re-uptake Inhibitors (SSRI) and who are pregnant or intend to become pregnant to discuss the situation with their doctor due to potential risks to the baby.

Health Canada stresses that patients should not stop taking SSRI medication without first consulting their doctors, as they could experience serious side effects.

Generally, SSRI treatment should only be continued if the benefits to the individual patient are thought to outweigh the risks to the unborn child, while also considering the benefits and risks of switching to another treatment option or stopping treatment altogether. These precautions and the possibility of adverse health effects in newborns are mentioned in the current Canadian prescribing information and consumer information for SSRIs.

SSRIs and other newer antidepressants prescribed for the treatment of depression include the following drugs:

Wellbutrin (bupropion)
Celexa (citalopram)
Cipralex (escitalopram)
Prozac (fluoxetine)
Luvox (fluvoxamine)
Remeron (mirtazapine)
Paxil (paroxetine)
Zoloft (sertraline)
Effexor (venlafaxine)
Zyban (bupropion) for smoking cessation

A study published recently in the New England Journal of Medicine suggests that use of SSRIs during the second half of pregnancy may be associated with a condition called persistent pulmonary hypertension of the newborn. Newborns with this rare but life-threatening condition do not receive enough oxygen in the blood and require intensive-care treatment to survive. According to the study, babies born with this condition were six times more likely than healthy babies to have been exposed to SSRIs. This information is considered to be preliminary at this time.

Numerous reports in Canada and abroad have already indicated that some children exposed to SSRIs and other newer antidepressants during pregnancy may develop serious complications at birth. An increase in the overall risk of major birth defects has also been associated with SSRI use.

Wellbutrin use comes with warning

Sun, 12 Feb 2006 00:00:00 -0800

Wellbutrin is one of several antidepressants that the U.S. Food and Drug Administration announced in 2004 could increase the risk of suicidal thoughts or behaviors in children or adolescents being treated for depression.

The agency required a “black box” warning for all antidepressants issued after October 2004. A similar warning followed for adults last year, although the FDA said it needs more time to study the clinical trials to ensure there is as high a risk as with adolescents.

In the meantime, the FDA has cautioned that adults on antidepressants should be monitored closely for any behavioral changes, especially when they start taking the drug or receive dosage changes.

Wellbutrin, manufactured by GlaxoSmithKline, works by correcting an imbalance in the brain of dopamine, one of several chemicals thought to be involved in depression.

The most common side effects reported are nausea, blurred vision, dizziness and headaches. It also has been associated with increased risks of seizures in some patients.

But unlike another class of antidepressants known as SSRIs, Wellbutrin seems to carry less risk of sexual side effects, which makes it especially appealing to adults.

The FDA advisory followed warnings for years from some researchers and consumer advocates about the potential dangers of antidepressants. In numerous cases around the country, attorneys and some health professionals have argued that there’s a link between suicides or horrific crimes and people who recently had been prescribed an antidepressant.

Others, however, say the drugs are highly effective and allow depressed patients to retake control of their lives, and that those benefits outweigh the risks to a small percentage of patients.

A study published in the American Journal of Psychiatry in January in response to Food and Drug Administration warnings looked at suicide rates among 65,000 Group Health Cooperative patients who had been treated with antidepressants.

It found a much higher risk among adolescents on medication than those taking a placebo. For adults, the study found that the risk increased during the first month of medication, but that it still was lower than the risk during the month before getting treatment.

Once outside the initial treatment phase, the rate of suicidal behavior dramatically decreases for everybody, the study found.

Depressed patients often come in at a peak in their distress, which makes it difficult to say that the medication triggered suicidal tendencies, said Wayne Katon, a psychiatry professor at the University of Washington. He noted that elderly men are 10 times more likely to commit suicide than adults under age 60, especially those with depression or chronic illness.

But side effects, especially during the first few weeks or whenever a dosage is altered, can exacerbate symptoms of depression.

That’s why it’s critical for doctors to follow up with their patients in one to two weeks.

“There are a lot of people with a depression or anxiety disorder who need antidepressants who are not getting good management,” he said. “The public has something to do with that.

“People come in wanting a pill. Americans are always looking for short-term fixes, like the latte to wake up today. A part of this is because it’s part of our society.”

Doctors also need to do a better job of educating patients about side effects and their disorders.

“In general, the FDA warning was to make sure patients get closer follow-up, which is something we’ve always recommended,” Katon said.

Each patient reacts differently to medications.

About 15 percent of patients experience side effects that force them to stop taking the medication, while another 10 to 15 percent have bothersome side effects that eventually subside, he said.

An elderly patient, for example, probably should start on a dosage lower than the standard because he or she might not metabolize the drug as well, he said.

FDA Warns About Antidepressants, Suicide

Fri, 01 Jul 2005 00:00:00 -0700

The Food and Drug Administration issued a second public warning Friday that adults who use antidepressants should be closely monitored for warning signs of suicide, especially when they first start the pills or change a dose.

Much of the concern over suicide and antidepressants has centered on children who use the drugs. The FDA last fall determined there is a real, but small, increase in risk of suicidal behavior for children and ordered the labels of all antidepressants to say so.

A year ago, the FDA issued a warning that adults, too, may be at increased risk. The agency began reanalyzing hundreds of studies of the drugs to try to determine if that's the case, and told makers to add or strengthen suicide-related warnings on their labels in the meantime.

Since then, several new studies have been published in medical journals about a possible connection. Citing them, FDA issued a new public health advisory reminding doctors and patients to watch closely for suicidal thinking or worsening depression and seek medical care if it happens.

It's a difficult issue to sort out because depression itself can lead to suicide and studies show that antidepressants have helped many people recover.

But there are concerns that antidepressants may cause agitation, anxiety and hostility in a subset of patients who may be unusually prone to rare side effects. Also, psychiatrists say there is a window period of risk just after pill use begins, before depression is really alleviated but when some patients experience more energy, perhaps enabling them to act on suicidal tendencies.

In addition to the advisory, the FDA also updated its Web site with a notice about a higher-than-expected rate of suicide attempts in research with the nation's newest antidepressant, Eli Lilly's Cymbalta. Those studies were in women trying Cymbalta as an incontinence treatment; it was never approved for that use. The FDA insisted when it approved Cymbalta last year that studies of depressed patients showed no suicide link.

FDA Orders Strong Antidepressant Warnings

Fri, 15 Oct 2004 00:00:00 -0700

All antidepressants must carry a "black box" warning, the government's strongest safety alert, linking the drugs to increased suicidal thoughts and behavior among children and teens taking them, the Food and Drug Administration said Friday.

Because the warnings are primarily seen by doctors, the agency also is creating an information guide for patients to advise them of the risk.

"Today's actions represent FDA's conclusions about the increased risk of suicidal thoughts and the necessary actions for physicians prescribing these antidepressant drugs and for the children and adolescents taking them," said Dr. Lester Crawford, acting FDA commissioner.

The drug labels also include details of pediatric studies which, thus far, have pointed to Prozac as the safest antidepressant for youths to take.

On average, 2 percent to 3 percent of children taking antidepressants have increased suicidal thoughts, independent experts, working with Columbia University, found.

The FDA announcement follows to the letter guidance from federal advisers. After searing and emotional public hearings one month ago, the advisers urged the agency to add its most strident warnings to the drugs.

The FDA said in a statement that it recognizes that depression in pediatric patients "can have significant consequences in pediatric patients if not appropriately treated. The new warning language recognizes this need but advises close monitoring of patients as a way of managing the risk of suicidality."

An information guide will be distributed with each antidepressant prescription. Parents will be advised to look for warning signs in children that include worsening depression, agitation, irritability, and unusual changes in behavior. Those worrisome signs could come within the first months of starting an antidepressant or when the drug's doses changes higher or lower.

In 24 trials involving more than 4,400 patients taking antidepressants, researchers found a greater risk of increased suicidal thoughts and behavior during the first few months of treatment.

Celexa, Prozac and Zoloft posed lower risks for children, researchers found, while Luvox, Effexor and Paxil had higher risks of increased suicidal thoughts and behavior.

Prozac is the only antidepressant approved by the FDA for use for treating depression in pediatric patients.

Anafranil, Prozac, Luvox and Zoloft have been used for treating obsessive compulsive disorder in pediatric patients.

The new warnings, however, will be carried by all antidepressants, including Anafranil, Aventyl, Celexa, Cymbalta, Desyrel, Effexor, Elavil, Lexapro, Limbitrol, Ludiomil, Luvox, Marplan, Nardil, Norpramin, Pamelor, Parnate, Paxil, Pexeva, Prozac, Remeron, Sarafem, Serzone, Sinequan, Surmontil, Symbyax,Tofranil, Tofranil-PM, Triavil, Vivactil, Wellbutrin, Zoloft and Zyban.

The agency's action comes at a time when it faces withering criticism for not acting sooner on antidepressants, and for the shortage of flu vaccine and the high-profile withdrawal of Vioxx for safety concerns.

Congressional investigations have focused on allegations the agency silenced its own employees who tried to raise safety concerns on the antidepressants and Vioxx.

FDA Admits Drugs' Risks

Tue, 14 Sep 2004 00:00:00 -0700

Top Food and Drug Administration officials said publicly for the first time Monday that scientific trials of frequently prescribed antidepressants have powerfully demonstrated that children who took the medications faced an increased risk of suicide.

Testifying before two FDA advisory committees, the officials said a recent study contracted by the FDA and conducted by Columbia University confirmed the findings of an internal analysis early this year: In clinical trials, the drugs almost doubled the incidence of suicidal behavior in children.

``What's striking about it is the consistency,'' said Dr. Robert Temple, director of the FDA's office of drug evaluation, referring to the medications' effects on young people.

More than 4,000 children ages 6 to 18 participated in the clinical trials. None of the children killed themselves, although hundreds experienced suicidal behavior or thoughts. Of the 40,000 adults who have participated in clinical trials for the antidepressants, 30 have committed suicide, according to the FDA.

The agency, under mounting criticism for its approach to regulating antidepressants for children, is seeking advice from the two committees on the necessity of further regulation. The committees are expected to announce their suggested regulatory approach today at the culmination of a two-day meeting.

Concerns about a possible link between the drugs and suicide were raised in the media and by some psychiatrists in 1990. The FDA convened an advisory panel on the topic but issued no warnings. Anecdotal evidence of such a link continued to accumulate, and in December the British counterpart of the FDA effectively prohibited physicians from prescribing a range of antidepressants to children, citing an increased risk of suicide.

In March, after hearings where parents told of the effects these drugs had on their children, the FDA ordered manufacturers of 10 frequently prescribed antidepressants Prozac, Zoloft, Paxil, Luvox, Celexa, Lexapro, Effexor, Wellbutrin, Serzone and Remeron to include warnings about an increased risk of deepening depression or even suicide on product labels and urged patients and their families to report any changes in behavior to their doctors.

Members of Congress from both parties have joined parents in criticizing the FDA for suppressing the results of the internal study, which showed a clear link between the drugs and youth suicide. That study became public after it was leaked to the news media.

But Temple said he was not sorry for waiting for the Columbia study before concluding that the data suggested a clear link between the drugs and suicidal behavior among children and teens.

It would be dangerous, he said, to prematurely rule out these drugs as possible treatment for childhood depression because there are few medical remedies available for the illness. Depression plays a significant role in suicide, the third-leading cause of death in teens.

``We've thought all along, it is extremely important to get as right an answer on this as we can,'' Temple told reporters.

Antidepressants Need Stronger Warnings

Tue, 14 Sep 2004 00:00:00 -0700

Antidepressants such as Paxil and Prozac should come with strong warnings that they raise the risk of suicidal thoughts and behavior in some children and teen-agers, a U.S. advisory panel concluded on Tuesday.

The U.S. Food and Drug Administration's panel of outside experts voted 15-8 to recommend warnings on the drug labels set off in a "black box," the strongest type of warning the government uses for prescription drugs.

Evidence from two dozen clinical trials of nine of the newest antidepressants showed children treated with the drugs were more likely to report suicidal thoughts or actions, panel members concluded. No suicides occurred during the trials.

"The purpose is to put physicians on notice that this group of medicines can cause problems," said panel member Dr. James McGough, a child and adolescent psychiatrist from Los Angeles.

Robert Gibbons, a panel member and statistician from the University of Illinois-Chicago, stressed the risk was "very small."

An FDA analysis concluded two or three out of every 100 young people treated with antidepressants might be at higher risk of suicidal behavior. In studies, worrisome actions ranged from writing a suicide note to attempting an overdose.

Any message in a black box would need to appear prominently in advertisements for the medicines, FDA officials said.

Prozac maker Eli Lilly said in a statement it "shares the concerns expressed by some committee members that (a black box) could discourage the use of appropriate treatment."

Lilly and other manufacturers promised to work with the FDA to decide how best to warn doctors, parents and patients and stressed the drugs' potential to prevent suicide.

"When people with depression are left untreated, 15 percent will actually commit suicide," Lilly said.

ALL NINE DRUGS STUDIED

The panelists said safety concern applied to all nine drugs studied, including Prozac, GlaxoSmithKline Plc's Paxil and Wellbutrin, Pfizer Inc.'s Zoloft, Forest Laboratories Inc.'s Celexa, Wyeth's Effexor, Solvay SA's Luvox and Akzo Nobel NV's Remeron were also reviewed.

Bristol-Myers Squibb's Serzone was also included, but the company discontinued the drug earlier this year.

The black box warnings should also appear on older antidepressants such as tricyclics, the panel said.

Data on suicidal behavior varied among drugs, but "we are unable to conclude any single agent is free from risk at this time," said Dr. Lauren Marangell, a panel member and psychiatrist at Baylor College of Medicine in Houston.

The black box should also convey results from studies of drugs that failed to show effectiveness in children, some panelists said. Only Eli Lilly and Co.'s Prozac has been proven effective and is FDA-approved for treating pediatric depression.

About 7 percent of antidepressant prescriptions are written for children, FDA officials said.

The FDA first became aware of a possible link to suicidal behavior in May 2003. Critics charge the agency was slow to act and instead chose to discount the findings of one of its own researchers.

In March 2004 the FDA advised doctors and parents to watch for signs of worsening depression or suicidal thoughts in patients taking the newer antidepressants.

But British authorities had already told doctors last year to avoid prescribing most antidepressants to children because of worries over possible suicidal behavior.

The FDA has committed to updating the drug labels, but has not said when officials will make a final decision. The agency usually follows the advice of its advisory panels.

Wellbutrin SSRIs Antidepressant Suicide Side Effects Injury Attorney

Tue, 14 Sep 2004 00:00:00 -0700

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Injured by Wellbutrin?

On December 13, 2006, the FDA announced antidepressants prescribed to young adults are risky. The agency proposed expanding the labels of all antidepressants to include an expanded warning of suicidal thoughts in patients ranging from 18-24 years of age. The newly presented change would expand a warning now on the labels that pertain only to children and adolescents treated with antidepressant drugs. The new label changes would also contain a suggestion that patients of all ages be carefully monitored, particularly when starting antidepressant treatment.

The FDA recently completed a bulk evaluation of 372 studies involving approximately 100,000 patients and 11 antidepressants, including Lexapro, Zoloft, Prozac and Paxil. When the results are analyzed by age, it becomes clear there is an elevated risk for suicidal thoughts and behavior among adults 18 to 25 that approaches that seen in children, the FDA said in documents released before their scheduled December 13, 2006 meeting of its psychopharmacologic drugs advisory committee.

In May 2006, GlaxoSmithKline and the FDA cautioned Paxil may raise the risk of suicidal behavior in young adults too and changed the drug’s label to reflect that risk.
Top Food and Drug Administration (FDA) officials have said publicly for the first time that scientific trials of frequently prescribed antidepressants have powerfully demonstrated that children who took the medications faced an increased risk of suicide. Testifying before two FDA advisory committees, the officials said a recent study contracted by the FDA and conducted by Columbia University confirmed the findings of an internal analysis early this year. In clinical trials, the drugs almost doubled the incidence of suicidal behaviour in children.

After hearings where parents told of the effects these drugs had on their children, the FDA ordered manufacturers of 10 frequently prescribed antidepressants: Prozac, Zoloft, Paxil, Luvox, Celexa, Lexapro, Effexor, Wellbutrin, Serzone and Remeron to include warnings about an increased risk of deepening depression or even suicide on product labels and urged patients and their families to report any changes in behaviour to their doctors.

Concerns about a possible link between the drugs and suicide were raised in the media and by some psychiatrists in 1990. The FDA convened an advisory panel on the topic but issued no warnings.

Antidepressant Risk for Heart Disease Patients
In addition to the aforementioned side effects associated with antidepressants, a new study has linked these drugs to an increased risk of death amongst patients with coronary artery disease. This study, which was conducted at Duke University, analyzed the survival rate of heart disease patients using antidepressants compared with those not using these drugs. During an average of three years of follow-up, 21.4% of the patients taking antidepressants died compared with 12.5% of those not on antidepressants. After adjusting for demographic factors, cardiac risk factors, scores on the Beck Depression Inventory test, and the presence of other illness, antidepressant use was an independent risk factor for mortality, increasing the risk by 62%.

Researchers do not fully understand why antidepressants increase the risk of mortality in these patients. However, their findings are statistically significant and show that these drugs do increase the risk of death in heart disease patients. Current and former heart disease patients should weigh the risks and benefits of antidepressants before using these medications.

If you or a loved one took Wellbutrin and suffered side effects, please fill out the form at the right for a free case evaluation by a qualified drug side effects attorney.