Yourlawyer.com (Celexa News)

Another Study Links Antidepressants To Birth Defects

Fri, 25 Sep 2009 00:00:00 -0700

More emerging research is pointing to links between antidepressant use and a greater chance for a particular heart birth defect, writes WebMD.

A Danish study of over 400,00 children born from 1996 to 2003, found that the risk increased when expectant mothers either take more than one selective serotonin reuptake inhibitor (SSRI) or switch SSRIs in early trimesters, said WebMD. Popular SSRIs include Prozac, Paxil, Zoloft, Celexa, and Lexapro, and are often prescribed to pregnant women suffering from depression, WebMD pointed out.

According to the study, when pregnant women took more than one SSRI, their babies experienced a four-fold increase in septal heart defects, a defect in the wall that divides the heart’s left and right sides, explained WebMD.

As we've reported previously, in late 2005, the U.S. Food & Drug Administration (FDA), sent an alert to physicians about early studies suggesting Paxil could be a contributor to heart defects in babies when taken by expectant mothers in the first trimester. WebMD noted that not only was Paxil singled out by the agency, but also since the warning, doctors are routinely known to switch pregnant women’s medication from Paxil to a different SSRI when pregnant or discussing become pregnant. That early switching has been linked to the infant heart defect. Also, said WebMD, citing recent studies, Paxil does not increase the risk of the specific heart defect versus other antidepressants; the Danish study found that Celexa and Zoloft in early trimesters was associated with the heart defect while the risk was not seen with Paxil or Prozac.

Septal heart defects occurred in 0.5 percent of children born to women not on SSRIs, while 0.9 percent of children born to mothers taking SSRIs were diagnosed with the defect. Lars H. Pedersen of Aarhus University called for larger studies to determine the safety of any one SSRI versus any others during pregnancy.

In a joint statement from the American College of Obstetricians and Gynecologists (ACOG) and the American Psychiatric Association (APA), the groups recommended that women who experience psychotic episodes, have bipolar disorder, are suicidal or have a history of suicide attempts should remain on antidepressants; women suffering from mild depression or who experienced few symptoms for six months or more could consider gradually reducing or stopping SSRI use under close physician supervision; and psychotherapy and other treatments might be an appropriate alternative in some, not all, pregnant women with depression, reported WebMD.

Antidepressants Linked to Sudden Cardiac Death in Women

Wed, 11 Mar 2009 00:00:00 -0700

A new study has concluded that women with no history of cardiac problems but who use antidepressants are at an increased risk for sudden cardiac death (SCD). HealthDay News reports that the reason for the link remains unknown, according to the researchers whose findings were published in the Journal of the American College of Cardiology.

"We suspect that their use is a marker for people with worse depression," explained the study’s lead author Dr. William Whang, an assistant professor of clinical medicine at Columbia University Medical Center in Manhattan. "The elevated risk seems more specific for antidepressant use, but that use may well be a marker of more severe symptoms," quoted HealthDay News. Whang noted that the link seemed to be physiological saying, “We found that women who had worse depressive symptoms had higher rates of risk factors such as hypertension, diabetes, and smoking.” As a matter-of-fact, the report indicated, said HealthDay News, women with clinical depression were at a two-fold risk of experiencing SCD.

The researchers looked at over 63,000 American women in the Nurses Health Study, said HealthDay, with no history of previous stroke or heart disease from 1992 to 2004, said Natural News, and found a link between depression and heart risk; however, the link between SCD and antidepressants was significantly more pronounced. Also, antidepressant use was not linked with an increased risk of cardiac arrest over fatal heart disease, only with the increased risk of SCD, reported HealthDay News. Prior research established the link between depression and an increased risk of death for those with heart disease, explained Whang, who noted, "But this was a group of women without heart disease, and that makes it different," said HealthDay News.

Natural News pointed out that the study found women with the highest risk for SCD and fatal coronary heart disease (CHD) expressed the most severe depression symptoms or were on antidepressant therapy. "We can't say antidepressant medications were the cause of higher risk of sudden cardiac death. It may well be that use of antidepressants is a marker for worse depression," said Whang, reported Natural News. "The biggest clinical implication is that management of coronary heart disease risk factors may be especially important for those with depressive symptoms. Taking care of those risk factors can modify the risk for coronary disease," warned Whang, according to HealthDay News.

To determine which women suffered from depression, the team reviewed their self-reported depression symptoms and use of antidepressants, for instance, Prozac, said Natural News. A link was clearly present with serious heart rhythm problems, which include those causing sudden death, said HealthDay News. The American Heart Association explained, said Natural News, that SCD causes sudden death from an unexpected loss of heart function.

SSRI antidepressants, such as Prozac, Lexapro, Zoloft, and Paxil have been described as safe for the heart; however, a number of cardiovascular side effects, such as irregular heart rhythms and potentially lethal arrhythmias, are known to occur in some taking these medications, said Natural News, noting that Prozac maker, Eli Lily, lists a variety of adverse cardiac symptoms on the official package insert for physicians.

Celexa, Lexapro Promotions Questioned

Thu, 26 Feb 2009 00:00:00 -0800

Even though Lexapro and Celexa were both proven to promote suicidal thoughts in children, Forest Laboratories chose to market its antidepressants to pediatric patients anyway, prosecutors at the U.S. Justice Department have charged.

According to the Wall Street Journal (WSJ), the same prosecutors have charged that Forest Labs also violated anti-kickback laws by paying doctors to prescribe Lexapro and Celexa to vulnerable, pediatric patients. A lawsuit filed by the department now accuses the drug maker of violating the False Claims Act when it marketed the drug, The civil complaint also accuses Forest of covering up a medical study that concluded that Lexapro and Celexa were not effective medications for children, said WSJ. The complaint was unsealed in Boston federal court yesterday.

According to Bloomberg.com, the complaint charges that Forest was unwavering in its marketing of the drugs. Knowing that they were ineffective in children and could also cause suicidal thoughts in pediatric patients, Forest went ahead and promoted Lexapro and Celexa for use in children, going so far as to cite a study that was more conducive to its needs and hiding the negative findings. Meanwhile, the U.S. Food and Drug Administration (FDA) never approved the drugs for use in children.

According to the DOJ, Forest’s bribes and inappropriate marketing resulted in false claims submission for reimbursement to federal health care programs said the Journal. Bribes included not just cash payments—falsely described as grants and consulting fees—but pricey meals and other expensive gifts which violated anti-kickback laws, said Bloomberg. “By knowingly and actively promoting these antidepressants for off-label pediatric use without disclosing the results of the negative pediatric study, and by paying kickbacks, Forest caused false claims to be submitted to federal health care programs,” Massachusetts U.S. Attorney Michael Sullivan said in the complaint, reported Bloomberg.

Now, under the federal False Claims Act, the DOJ is looking for triple the financial damages from Forest in addition to other penalties; the total compensation sought is unknown, said the Journal. Bloomberg noted that under the Act, the government is eligible to receive treble damages and civil penalties of up to $11,000 per violation.

This case and others may be evidence that the DOJ is making a concerted effort to crack down on the illegal drug marketing practices. The Journal pointed out that just last week, the DOJ joined a whistle blower lawsuit against Johnson & Johnson in which the drug maker is charged with illegally marketing its cardiac medication Natrecor. Also, last month, Pfizer Inc. and Eli Lilly & Company both agreed to payouts in two separate cases involving illegal marketing, said the WSJ. Pfizer agreed to pay over $2 million in response to charges it illegally promoted it now-withdrawn painkiller Bextra. Eli Lilly agreed to pay $1.4 billion in fines to settle similar claims over its antipsychotic Zyprexa.

Antidepressants Linked to Stomach Bleeding

Tue, 08 Jul 2008 00:00:00 -0700

A Spanish study in the Archives of General Psychiatry is reporting this week that antidepressants taken by millions of people may actually increase a patient’s risk of developing stomach ulcers. The drugs, which are known as selective serotonin reuptake inhibitors—or SSRIs—include Eli Lilly & Company’s Prozac, Forest Laboratories Inc.’s Celexa and Lexapro, GlaxoSmithKline Plc.’s Paxil, and Pfizer Inc.’s Zoloft.

According to Francisco de Abajo, from the Spanish Agency for Medicines and Healthcare Products, these drugs could trigger gastrointestinal bleeding in one out of every 2,000 patients. The study found that the risk also applies to Wyeth's innovative pill Effexor, but with Effexor, the risk increases to one in 250 patients when aspirin or pain drugs also are taken. The researchers found that these medicines interfere with platelets, “a critical part of the body's normal clotting process.” “The risk … should be considered, de Abajo said, adding that  "The risk … may be much more important in patients," with a history of ulcers or who regularly use medications such as aspirin and pain pills. The researchers studied the medical records of 1,321 patients with upper gastrointestinal tract bleeding, and compared them with a healthy group of 10,000 people. Of those with bleeding, 5.3 percent were taking SSRIs as compared with three percent of the healthy group. Of those who experienced bleeding, about 1.1 percent were taking Effexor, a different type of antidepressant, compared with 0.3 percent among those without an ulcer.

de Abajo suggests that proton pump inhibitors—drugs that suppress the production of acid in the stomach—such as Prevacid, Prilosec, Nexium, and Protonix, could help minimize the bleeding “for those most vulnerable and should be considered.” AstraZeneca, Plc., the maker of Nexium and Prilosec, helped fund the Spanish study.

Meanwhile, the Food & Drug Administration (FDA) has investigated a suspected link between cardiac trouble and acid-reflux drugs Prilosec and Nexium. Also, because both drugs are proton-pump inhibitors, they may be overly effective at stopping stomach acid production, raising pneumonia, bone loss risk, and fracture risk, this by over 40 percent in patients on long-term use.

In a study we reported on in February that was conducted by British researchers on the effect of some antidepressants found that they may only really be truly effective in the most severely depressed of patients. The study also found that these antidepressant medications actually work no better than placebos in many patients taking them and that the patients fared the same whether on a placebo or on one of the antidepressant medications represented in the study: Prozac, Effexor, and Paxil.

Meanwhile, there have been warnings that antidepressants might increase suicidal behavior in youth. U.S. and European regulators sent out a series of public health warnings in 2003 after clinical trials showed the drugs increased the risk of suicidal thoughts and behaviors in children and teens. In 2004, the FDA issued its strongest warning—a black box—on all antidepressant use in children and teens to draw attention to these medications’ possible risks.

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.

FDA panel to review safety of 16 drugs in children

Wed, 15 Nov 2006 00:00:00 -0800

A Food and Drug Administration panel is set to meet Thursday to discuss the safety review of 16 drugs, including flu drug Tamiflu, in pediatric patients.

The pediatric advisory committee will evaluate new and updated reports by the FDA staff that include information on the drugs' safety compiled over a year. The panel will then make recommendations that could include label changes or further investigation of adverse events.

The FDA isn't required to follow the panel's suggestions, but it usually does.

Although the panel was to issue an opinion on Tamiflu's label Thursday, on Tuesday its manufacturer, Roche Holding AG (RHHBY), said it would follow the FDA staff's recommendation in the report and update the label to warn patients of potential abnormal behavior during treatment, including delirium and hallucinations.

In its report, the staff said the label should be changed following a review that found 103 cases of "neuropsychiatric adverse events," including the death of a 14-year-old boy who fell after climbing on his condominium balcony's railing.

According to documents posted on the FDA Web site ahead of Thursday's meeting, eight drugs under review didn't raise any safety concerns. They include cholesterol-lowering medications Lipitor from Pfizer Inc. (PFE) and Zocor from Merck & Co. (MRK), Eli Lilly & Co.'s (LLY) cancer drug Gemzar, and Johnson & Johnson's (JNJ) Ditropan to treat bladder instability.

The other eight drugs either presented new unlabeled safety concerns or "other attributes," including labeled but "serious adverse events of interest" and past safety concerns, the FDA said.

Included in this group are Pfizer's Zyvox, GlaxoSmithKline PLC's (GSK) Zofran and Avandia, Forest Laboratories Inc.'s (FRX) Celexa, Novartis AG's (NVS) Trileptal, Wyeth's (WYE) Rapamune and Abbott Laboratories' (ABT) Norvir.

In an updated report for depression drug Celexa, the FDA staff identified three new cases associated with QT prolongation, which can cause a fatal arrhythmia, since August 2003. The FDA requested the review following a prior report that found a possible association between the drug and the problem in all ages.

"However, this updated review of three new cases didn't find any well-documented cases of QT prolongation associated with using regular doses of (Celexa) in pediatric patients," the FDA staff concluded.

On Pfizer's Zyvox, which is indicated for treatment of certain bacterial infections, the FDA staff found six unlabeled events of "cardiac nature" during the one-year review. The report, however, said the cases "cannot be definitively associated" with the drug.

In the report on epilepsy drug Trileptal, the FDA staff recorded 84 adverse events in children taking the drug in the year-long review. Those events included one death, 52 unlabeled and 31 labeled cases. The staff said the unlabeled cases were too few to "characterize any one adverse event as a potential safety signal."

On Wyeth's Rapamune, the investigation found 19 pediatric cases of adverse events, including two reports of fluid collection that develops between the lining of the heart and the heart itself, and one report of cerebral bleeding.
Rapamune is indicated for the prophylaxis of organ rejection in patients ages 13 or older receiving a renal transplant. The FDA staff, however, said the majority of children it studied were under 12 years of age.

The report found it was "premature" to determine if the drug "played a clear role" in the adverse events reported.
On Glaxo's Zofran, used to prevent nausea and vomiting associated with chemotherapy and radiotherapy for cancer, the FDA staff identified 20 adverse events over a year, including one death. The report said, however, that most patients had underlying conditions or were taking other medication, making it difficult to link the events to the use of Zofran.
In the review of diabetes drug Avandia, the staff found two adverse cases during the one-year period, one involving accidental ingestion and the other involving behavioral changes. It said there were too few reported events to draw any safety conclusion.

On Abbott Labs' Norvir, used to treat HIV patients, the review found 33 adverse events in children in a period of one year, including skin reactions, anemia and pancreatitis. There were three deaths, none directly related to the use of the drug, the FDA said, adding it didn't find any safety concerns.

In the reports, the staff said it will continue to monitor adverse events related to the drugs. The FDA panel will meet at the agency's headquarters in Rockville, Md.

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.

Study: Antidepressants pose risks for newborns

Thu, 09 Feb 2006 00:00:00 -0800

A UCSD study released today is fueling concerns about the effects of certain antidepressant drugs on pregnant women, saying that their use late in pregnancy can significantly increase the chance of deadly lung problems in newborns.

Normally, the lung disorder is rare, with one to two per 1,000 births. But when pregnant women took the drugs in question after the 20th week of pregnancy, the incidence rose to six to 12 per 1,000 births, a report by Dr. Christina Chambers and colleagues at UC San Diego found.

The antidepressants that increased that risk are in a class called SSRIs or selective serotonin reuptake inhibitors. They include citalopram, fluoxetine, paroxetine and sertraline sold under 19 brand names, including Celexa, Prozac, Paxil and Zoloft.

Babies born with the lung disorder, persistent pulmonary hypertension or PPH, often require mechanical assistance to breathe. Between 10 percent and 20 percent will die soon after birth, while others will have developmental delays, hearing loss and brain abnormalities.

Chambers said she didn't want pregnant women now taking the drugs to become scared.

“Ninety-nine women in 100 who take SSRIs late in pregnancy will not have a baby with PPH, so the risk is fairly low,” Chambers said. “But the risk is higher than if the women don't take the drugs, so I think it's important to get the information out there so health providers and women aren't navigating in the dark.”

In a Washington news conference yesterday, a U.S. Food and Drug Administration official called Chambers' findings significant and “worrisome,” especially because 10 percent to 15 percent of women of reproductive age have major depression and are the biggest users of antidepressant drugs.

Dr. Sandra Kweder, deputy director of the FDA's Office of New Drugs, added that the report comes only a few weeks after a flurry of other large studies on other problems with antidepressants, particularly SSRIs.

Kweder said the FDA will issue a “public health advisory” in the next few days that may include a recommendation that manufacturers of antidepressant drugs conduct additional safety studies.

Women should not go off their antidepressants cold turkey, Kweder said.

“Don't panic,” she said, adding that women with concerns should talk to their doctors. A decision about whether to stop taking the drugs should take into account the severity of the depressive symptoms that prompted the prescription.

“Stopping these medicines on your own can sometimes create more problems than it solves,” Kweder said. “Often these medicines are associated with withdrawal symptoms, which can be problematic for many patients.”

Recent reports have linked SSRIs and other antidepressants with problems in newborns such as not eating properly, jitters and seizures. One study published last week in The Archives of Pediatrics & Adolescent Medicine said 30 percent of infants exposed to SSRIs in the womb develop sugar imbalance, sleep disturbances and difficulty eating that show up like the symptoms of drug withdrawal.

In December, the FDA warned that the use of one SSRI, paroxetine sold as Paxil, during the first trimester is associated with increased risk of birth abnormalities such as cardiac defects.

Another study published last week in the Journal of the American Medical Association dispelled a previously held belief that hormonal and other biochemical changes in pregnant women somehow protected them from clinical depression.

Dr. Lee S. Cohen, a psychiatrist at Massachusetts General Hospital and lead author of the report, wrote that 68 percent of women who discontinued antidepressant treatment after getting pregnant had a significant relapse into depression before giving birth.

Published reports suggest that the use of antidepressants by pregnant women results in some negative impact for as many as 30 percent of their newborns, although most of the time the problems are short-lived and reversible.

“Most studies have not suggested a smoking gun for long-term problems with the use of SSRIs,” said Dr. James Mills, a researcher with the National Institute of Child Health and Human Development. “But that's not true for PPH. In that group (of newborns) the story is very different” because PPH is so serious.

In Chambers' study, the higher incidence of PPH did not occur in women who took non-SSRI antidepressants. These include tricyclics such as amitriptyline sold as Elavil, bupropion sold as Wellbutrin, venlafaxine sold as Effexor and trazodone sold as Desyrel.

The higher risk also was not seen in women who stopped taking SSRIs by the 20th week of pregnancy, her study found.

Asked if she she would take an SSRI if she were pregnant and depressed, Chambers said that it would depend on how depressed she was, what other coping mechanisms were available and whether she were given options for alternative medications.

She stressed that more research is needed to look further into the future for children exposed in the womb to antidepressants.

Chambers urged the FDA and drug companies to develop “better information about this group of antidepressants, and as it is developed it needs to be disseminated.”

The UCSD study, done with colleagues in Boston, Toronto and Philadelphia, is published in today's New England Journal of Medicine. Participants were enrolled from more than 100 hospitals, including 17 in San Diego County.

As they read Chambers' study, San Diego area psychiatrists yesterday said they were rethinking the way they prescribe this class of medication to patients who may be thinking of having children.

But sometimes they have no choice, they said, in the case of a patient who is severely depressed and for whom other categories of antidepressants don't work.

“Sometimes there is no other way to help a woman who is in a severely restless and agitated state,” said Dr. Rodrigo Munoz, a psychiatrist and former president of the San Diego County Medical Society.

“No doubt giving the woman any medication during pregnancy is taking a risk.”

Mission Valley psychiatrist Dr. Catherine Moore said she takes into account how sick her patient is.

“Some women are so depressed, they're not eating well, and that may have an effect on a baby's low birth weight or cause developmental delays,” Moore said.

That absolutely needs to be taken into account, she said.

The FDA's Kweder said the Chambers study, added to the others, “absolutely highlights the critical need for more and better information about the safety and best uses of drugs during pregnancy.

“What you're seeing is that our society's increasing reliance on pharmaceuticals is finally extending to pregnant women, but there's a paucity of information designed to look at this in a systematic way,” Kweder said.

Analysis: SSRIs' risk to infants

Mon, 06 Feb 2006 00:00:00 -0800

The class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) is facing more bad news this week with the release of a study indicating that pregnant women's use of the drugs may be dangerous to their newborn infants.

The study, which appears in the February issue of Archives of Pediatrics and Adolescent Medicine, found that nearly one-third of newborn infants whose mothers took SSRIs during pregnancy experienced withdrawal symptoms that included high-pitched crying, tremors and disturbed sleep.

Natalie Taylor, an analyst with Decision Resources, said the finding could affect the SSRI market but noted that the field is already leveling off due to another danger previously linked to the drug class, an increased risk of suicidal behavior and thoughts in children and adolescents.

The suicidal risk, first publicized in late 2004, prompted the Food and Drug Administration to add a black-box warning to top-selling SSRIs like GlaxoSmithKline's Paxil and Pfizer's Zoloft.

Aside from the bold new warnings on SSRI labels, Taylor added, many of the medications have gone off patent or will soon.

"This might have an impact, but I think in any case the bottom line is that you need to weigh the benefits with the risks," she told United Press International.

The symptoms of major depression are severe enough that it may warrant putting a pregnant woman on an SSRI even if that does increase the risk of withdrawal symptoms in her infant, Taylor said. But if the patient has a milder case of depression, it might be worth reconsidering whether to put her on the medications, she said.

Overall, "the market (of SSRIs) is plateauing," Taylor said.

In the study, a team of researchers led by Gil Klinger of Tel Aviv University assessed withdrawal symptoms in 60 newborn infants who had prolonged exposure in the womb to SSRIs, including GlaxoSmithKline's Paxil, Lilly's Prozac, Forest's Celexa, Pfizer's Zoloft and Wyeth's Effexor.

Eighteen of the infants had symptoms of withdrawal, including eight with severe symptoms and 10 with milder symptoms.

"The high prevalence of neonatal abstinence syndrome in infants exposed to SSRIs in utero should be brought to the attention of family physicians, psychiatrists, gynecologists, pediatricians and mothers," Klinger and colleagues wrote in the journal.

"Because maternal depression during pregnancy also entails a risk to the newborn, the risk-benefit ratio of continuing SSRI treatment should be assessed," the researchers said.

They also recommended that infants of mothers taking SSRIs should be monitored closely after birth for a minimum of 48 hours and that "follow-up of exposed infants, particularly those who develop severe symptoms, is needed to assess the long-term effects of prolonged exposure to SSRIs."

Neonatal safety is an issue that apparently neither the FDA nor most SSRI manufacturers want to discuss. UPI contacted the FDA and several manufacturers, including Forest Laboratories, Pfizer and GlaxoSmithKline, but only Eli Lilly, which makes Prozac, responded.

"Lilly does not and has never promoted the use of Prozac in pregnant or nursing mothers," Lilly spokeswoman Heather Lusk told UPI.

Nevertheless, Lusk said, "Decisions regarding the use of anti-depressants during pregnancy should be made after considering an appropriate benefit-risk assessment by the attending physician. Absent such a determination, conclusions resulting in discontinuation of Prozac or any other anti-depressant treatment may result in serious health consequences from untreated maternal depression."

SSRIs came under fire in 2004 when British researchers obtained unpublished studies from manufacturers and concluded the medications (except for Prozac) appeared to increase the risk of suicide and suicide attempts in children.

The FDA is currently reviewing studies to determine if the same risk is present in adults. The agency said last July that it could take more than a year to complete its review.

WARNING: Withdrawal Reactions With Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants

Thu, 01 Dec 2005 00:00:00 -0800

A withdrawal reaction has been reported with all SSRI antidepressants: citalopram (CELEXA); escitalopram (LEXAPRO), fluoxetine (PROZAC, SARAFEM); fluvoxamine (LUVOX); paroxetine (PAXIL); and sertraline (ZOLOFT).

The symptoms generally start within one to three days after stopping the drug and generally resolve within one to two weeks after the drug has been discontinued. Withdrawal symptoms may occur even when the dosage of the drug is gradually decreased. The main symptoms of this reaction are dizziness, vertigo, incoordination, nausea and vomiting, and flulike symptoms that include fatigue, lethargy, muscle pain, and chills.

Healthcare professionals were notified on Sept. 27, 2005 that the professional product labeling for the selective serotonin reuptake inhibitor (SSRI) antidepressant paroxetine (PAXIL, PAXIL CR) was being updated to warn of major congenital malformations (birth defects), primarily heart malformations, in children born to women taking the drug during their first trimester of pregnancy.

Paroxetine was first marketed in the U.S. in December 1992 and last year, sales of the drug exceeded $824 million. Paroxetine is produced by GlaxoSmithKline of Research Triangle Park, NC.

The warning was based on a study that the FDA had asked GlaxoSmithKline to conduct. The study used two insurance company databases that store medical and pharmacy claims from health plans throughout the U.S. All women dispensed an antidepressant and who had delivered a live child between May 2000 and June 2003 were identified for the analysis.

The study suggested an over two-fold increase in the risk of major congenital malformations when paroxetine was taken compared to other antidepressants. This type of statistical research is not considered as reliable as a randomized “gold standard” study, which might support a conclusion that paroxetine causes birth defects. But it is more than sufficient to warn women of the possibility.

A more complete description of this study can be found on GlaxoSmithKline’s Web site at: http://ctr.gsk.co.uk/Summary/ paroxetine/epip083.pdf.

Parker & Waichman, LLP Urges Current and Former Bextra and Celebrex Users to Explore Legal Options; Firm Continues to Investigate Cases Involving Serious and Fatal Side Effects

Tue, 12 Apr 2005 00:00:00 -0700

Parker & Waichman, LLP (http://www.yourlawyer.com) has been contacted by numerous current and former Bextra users who believe they were injured as a result of using the drug. Parker & Waichman, LLP continues to evaluate cases and consult with prospective clients who have experienced heart attacks and strokes as well as those who have been diagnosed with Stevens Johnson Syndrome and Toxic Epidermal Necrolysis during the use of Bextra. Bextra is a COX-2 arthritis pain reliever manufactured by Pfizer, Inc. (NYSE:PFE - News) that was removed from the market on April 7, 2005.

Parker & Waichman, LLP and Seeger Weiss LLP filed the first lawsuit in the United States in 2004 against Pfizer claiming their clients sustained injuries and resulting death as a result of ingestion of the drug Bextra.

Parker & Waichman, LLP has also received a significant amount of inquiries from patients who suffered heart attacks and strokes while using Celebrex. Both Bextra and Celebrex patients can receive a free case evaluation by visiting http://www.bextralegalhelp.com and http://www.celebrexlawyernetwork.com.

Based on the number of Celebrex inquiries and the research data available, Parker & Waichman, LLP supports Public Citizen's view that Celebrex should also be removed from the market. Parker & Waichman, LLP believes that the failure to remove Celebrex from the market puts millions of people at an unnecessary risk.

An unpublished study finished in 2000 indicated increased cardiac risks associated with Celebrex. A more recent study sponsored by the National Cancer Institute discovered that Celebrex's risk of causing a major cardiovascular event was two-and-a-half times greater than that for people taking a placebo. In 2004, almost twice as many prescriptions were written for Celebrex as for Bextra -- 23.9 million prescriptions compared to 12.9 million.

``The removal of Bextra is a step in the right direction but we cannot ignore the high rate of serious side effects associated with Celebrex,'' commented Jerrold S. Parker, one of the founding partners of Parker & Waichman, LLP. ``We continue to believe that Celebrex is a dangerous drug that is no more effective in treating pain and no better tolerated than traditional NSAIDS. We will continue to represent victims of all COX-2 drugs whose lives have been impaired or lost.'' For more information on Celebrex, please visit http://www.yourlawyer.com/practice/overview.htm?topic=Celebrex. For more information on Bextra please http://www.yourlawyer.com/practice/overview.htm?topic=Bextra

For more information on Parker & Waichman, LLP please visit: (http://www.yourlawyer.com) or call 1-800-LAW-INFO (1-800-529-4636). For more information on Public Citizen please visit http://www.worstpills.org.

Contact:

Parker & Waichman, LLP
David Krangle, Esq.
(800) LAW-INFO (800-529-4636) (toll free)
dkrangle@yourlawyer.com
www.yourlawyer.com

FDA Tells Pfizer To Pull Bextra Off Market

Thu, 07 Apr 2005 00:00:00 -0700

Food and Drug Administration officials Thursday told Pfizer Inc. to take its COX-2 drug Bextra off the U.S. market and put a warning on Celebrex.

The FDA, based on recommendations from its Arthritis and Drug Safety and Risk Management Advisory Committee following a hearing in February, also asked manufacturers of all other prescription non-steroidal anti-inflammatory drugs to revise their labels to include the same box warning included on Celebrex.

Drugmakers selling NSAIDs also will have to include a medication guide for patients advising them of the potential for adverse events such as heart attack, stroke and gastrointestinal bleeding associated with this class of drugs.

Manufacturers of over-the-counter NSAIDs were asked to include more specific information about potential side effects, including a warning about potential skin reactions.

FDA began to investigate the COX-2 drugs last fall, and then included all NSAIDs, following studies that showed Merck's Vioxx, a COX-2 arthritis drug, doubled a patient's risk of heart attack when taken longer than 18 months.

The COX-2 Dilemma: Risking Heart Problems To Ease Pain

Wed, 02 Mar 2005 00:00:00 -0800

When she was just 18 months old, Melissa Hafeli was diagnosed with rheumatoid arthritis.

When she was just 12 years old, she was diagnosed with a stomach ulcer. Her doctor blamed it on the aspirin and naproxen she had been taking for her arthritis.

When she was 26, Hafeli switched to a new drug called Celebrex. Her doctor said it would be safer for her stomach.

Now 32, Hafeli isn't sure what to think about her arthritis medication, one of the so-called COX-2 inhibitors facing intense scrutiny by the Food and Drug Administration. "Sometimes," says Hafeli, of Nashville, "I choose not to think about it."

Last month, an FDA advisory panel unanimously concluded that Celebrex and its cousins, Bextra and Vioxx, significantly raised the risk of heart attack and stroke. Still, a slim majority recommended that the drugs could still be sold, even Vioxx, whose maker, Merck, took it off the market last September because of the safety concerns.

The panelists also noted that little is known about the long-term safety of many older drugs taken for arthritis pain and inflammation.

Patients and their doctors are left trying to figure out the new math of arthritis medications: With COX-2 inhibitors, is an increased risk of cardiovascular problems worth the possibility of fewer stomach complications? If not, is the risk of stomach problems from older drugs such as ibuprofen plus their generally unknown effect on the cardiovascular system worth the pain relief they provide?

Staying on drugs despite risk

"This is a wake-up call for all of us," says Sara Walker, a doctor with the Missouri Arthritis Rehabilitation Research and Training Center. "There are many problems that a simple pill can't or won't fix. We have to individualize every case."

Apparently, many patients and doctors already have calculated that the risks from taking COX-2 inhibitors or older prescription anti-inflammatory pain relievers outweigh their benefits. A recent report from IMS Health, a market research firm, shows that the U.S. market for COX-2 inhibitors and the older prescription anti-inflammatory pain relievers had dropped 9% by the end of last year. Meanwhile, total sales of non-prescription arthritis drugs in the last quarter of 2004 were up 8% compared with the last quarter of 2003, according to ACNielsen.

Bextra fan Rosie Shiver, 47, bristles at the suggestion that she could do just as well on an over-the-counter arthritis drug.

Shiver says she tried naproxen for her spondylolisthesis, a type of arthritis of the spine, but after a few weeks it was like taking a sugar pill. Eventually, she says, a hiatal hernia gave her chronic heartburn, which made COX-2 inhibitors attractive.

Vioxx left her nauseated, and Celebrex didn't relieve her symptoms, says Shiver, a resident of Lake Placid, Fla., who had to give up teaching years ago because of her health problems. She went on Bextra in October of 2002.

"It worked right out of the chute," she says. Sure, Bextra makes her ankles swell, Shiver says, but she doesn't necessarily believe it's bad for her heart.

Hafeli, a state employee, says she has no options other than a COX-2 inhibitor for her "pretty severe" arthritis. A year ago, though, Hafeli decided to cut her daily 400-milligram dose of Celebrex in half. "I don't like to take a lot of medication," she explains.

The 200-milligram dose appears to be safe, the FDA advisory panel concluded. But in mid-December, Hafeli says, she began having chest pain. "The tests were all negative. We're just not sure what that was."

Concerned about her heart, Hafeli tried taking 200 milligrams of Celebrex every other day. That lasted about two weeks, she says. "Those off days were too much."

Her experiment proved that Celebrex worked, Hafeli says, "but it was kind of disheartening that I couldn't get off of it.

"It's just hard to gauge whether the risks outweigh the real pain alleviation it provides."

COX-2 inhibitors may remain the best choice for rheumatoid arthritis patients who require medication for pain and inflammation on a daily basis, says Walker, a professor of internal medicine at the University of Missouri.

But the new information about cardiovascular risk "will cause us to look very hard at our patients with osteoarthritis," whose disease usually does not involve inflammation, Walker says. For those patients, the best choice might be non-drug options, such as glucosamine, exercise or weight loss, she says, noting that a drop of just 10 or 15 pounds can relieve the pain of osteoarthritis in weight-bearing joints.

Are any COX-2s safe?

Those non-drug alternatives wouldn't much help Eileen Lacijan, who has osteoarthritis in her thumbs. She began taking Vioxx in March of 2000 and, because it bothered her stomach, switched to Celebrex the following June.

"I was pain-free for a long time," says Lacijan, 57, an Arnold, Md., nurse who directs a hospice program. "My grandson was born in May and I started knitting him a sweater." By last July, though, the Celebrex had stopped working, so Lacijan switched to Bextra.

A month later, she had a heart attack. Her blood pressure and cholesterol were fine, and a catheterization after her heart attack found no blockage.

"I don't really know if that's what caused the heart attack," Lacijan says of her more than four years on COX-2s. "I don't know if I will ever know."

After her heart attack, Lacijan switched to Mobic, now the fastest-growing prescription arthritis drug that, some scientists say, is more like a COX-2 inhibitor than not.

Lacijan told her story to the FDA panel. As she parked before speaking at the meeting, she heard a radio news report about FDA scientist David Graham's report to the panel that morning. His analysis of California Medicaid patients suggested that Mobic might be as risky for the heart as Vioxx.

"Awww, great," Lacijan recalls thinking. "I've got to talk to my rheumatologist and see what she thinks."

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.

Prozac Linked To Child Suicide Risk

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

Prozac, the only antidepressant certified as safe for children, may make kids more suicidal, according to evidence out Monday.

A large new study added to previous research on Prozac shows that kids taking the drug have about a 50 percent higher risk of suicidal thoughts and suicide attempts than those getting placebos, says Robert Temple, director of the Office of Drug Evaluation at the Food and Drug Administration.

Temple spoke at the first day of hearings on potential label changes for antidepressants taken by more than a million children and teenagers. The discussion continues today, and an advisory committee could end the day by asking for tougher warning labels on all antidepressants taken by kids. The FDA typically follows the advice of its advisory committees.

Following a February hearing, the FDA in March asked drug companies to relabel 10 antidepressants, warning that young patients should be watched for worsening depression and anxiety. Critics at the time derided that move as "too little, too late," considering that, in December, British drug regulators had advised doctors to prescribe only Prozac for depressed kids.

Other major antidepressants prescribed for kids already have been found to raise the risk of suicidal behavior. Prozac had been an exception. "What's interesting and persuasive is that these studies now all lean the same way," Temple says.

So far, only Prozac has been found to be effective in children and teens, although the other drugs, approved for adults, are prescribed to children as an off-label use.

There were no suicides in the antidepressant studies of about 4,600 children. The increased risk for suicidal behavior is small: About two to three kids in a group of 100 become more suicidal because they're on antidepressants, says Tarek Hammad, medical reviewer for the FDA.

Dozens of parents testified at the hearing that antidepressants had caused their children to kill themselves or others. Their claims were "passionate and plausible," says psychiatrist Wayne Goodman, chairman of the FDA advisory panel.

But other parents and psychiatrists said the popular pills, such as Zoloft and Celexa, are saving lives every day.

Drug company spokesmen argued that antidepressants are safe. Company studies show most suicide attempts by children on Zoloft are linked to stress, not to taking the drug, says Steve Romano of Pfizer Inc., which makes Zoloft.

Although antidepressants seem to generate more suicidal behavior, "we can't forget all those who are protected from suicide by treatment," Goodman says.

There may be a group of kids who are particularly vulnerable to dangerous effects, but the limited studies so far don't suggest how they can be identified, FDA officials say.

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.

Child Antidepressants Must Have Warnings

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

Antidepressants should come with the nation's strongest warning in a black box on the label that they can sometimes spur suicidal behavior in children and teenagers, the government's scientific advisers decided Tuesday.

It's a rare risk, and therefore families need detailed information on how to balance that concern with the need to treat depression, which itself can lead to suicide, cautioned advisers to the Food and Drug Administration.

So antidepressants prescribed to minors also should come with an easy-to-read pamphlet that explains how to decide if the child is an appropriate candidate and what are the warning signs of suicide, the panel concluded. Also, FDA should consider the extra step of making parents sign a form that they understand the risks before the child receives the first pill.

There may be a backlash to such strong warnings, cautioned FDA advisory committee chairman Dr. Wayne Goodman, psychiatry chairman at the University of Florida.

"It will make prescribing more difficult. I anticipate there will be alarm from parents and the child," said Goodman, who still backed the step on a 15-8 vote. "I think that's worth that complication, because it will raise the threshold to prescribing" these drugs to minors.

The drugs seem to help some desperately ill children even though only one, Prozac, has won FDA approval as effective for pediatric depression, said panelist Jean Bronstein, a California nurse who opposed the black-box warning.

"The biggest message I heard from the consumer is they want to be warned about what the risk is," she said, referring to hours of emotional testimony Monday from families who blamed their children's suicides on drugs they didn't know might be risky.

Tearful families greeted Tuesday's decision with applause.

The FDA isn't bound by its advisers' recommendations but usually follows them. FDA drug chief Dr. Robert Temple said a decision could come within months but noted the advisers weren't unanimous: "When the decision is divided, it's less of a sure thing."

The FDA for months called any link with suicidal worsening unproven, but its latest analysis marks a sharp reversal: For every 100 youths given an anti-depressant, two or three may display increased suicidal thoughts or behavior due to the drug.

The controversy erupted last year, when British health authorities declared that most popular antidepressants might sometimes increase the risk of suicidal behavior in children and teenagers. They declared all but one Prozac unsuitable for depressed youth, but stopped short of a ban.

The FDA stresses that 24 studies of 4,000 youths found none who killed themselves.

Still, in March, the FDA strengthened anti-depressant labels to urge close monitoring of patients for suicide warning signs, including increased agitation or hostility, especially when they first start the pills or change a dose.

It called this week's two-day meeting to see what other safety changes are needed.

Only Prozac has won FDA approval that it truly eases depression in youth. While it is legal for doctors to prescribe adult drugs for children anyway youths account for 7 percent of anti-depressant prescriptions even a rare side effect raises more concern if the drug brings no benefit.

Still, other antidepressants shouldn't be banned for children, FDA's advisers stressed. About 10 percent of youths suffer from depression. The illness itself carries a 15 percent risk of suicide if untreated, said Dr. Matthew Rudorfer of the National Institute of Mental Health.

And Prozac doesn't work for everyone, noted University of Mississippi pharmacist Barbara Wells. Those children "certainly deserve to have access to other drugs."

Some studies suggest a greater risk for certain drugs, such as Effexor, and initial worries about antidepressants focused on a newer drug family called SSRIs.

"We are unable to conclude that any single agent is free from risk at this time," the advisers voted unanimously, urging that new warnings cover all pediatric anti-depressant use. That's because studies of the issue so far are small and flawed.

The suicide risk can occur not only when anti-depressants are prescribed for depressed youth but for other conditions, too, such as obsessive-compulsive disorder, Goodman added.

A black-box warning would make a huge difference in alerting patients to risks, said Kathleen Bodnar, whose 21-year-old daughter killed herself last March while taking Celexa. She had switched to that drug from a liver-damaging competitor more than a year earlier, when "she demanded that her doctor give her something safe."

The drug industry said Tuesday it supports stronger warnings but wouldn't comment on the black-box step, which it often opposes.

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.

Celexa Suicide Side Effects Attorney

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

DOWNLOAD OUR CELEXA INFORMATION PACKAGE

Injured by Celexa?

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.

Celexa, manufactured by Forest Pharmaceuticals, hit the U.S. market on July 17, 1998. Celexa is a SSRIs (Selective Serotonin Reuptake Inhibitors) a newer and more commonly prescribed antidepressant. Because the Food & Drug Administration (FDA) has not approved the use of Celexa for pediatric depression, Forest has been legally barred from promoting them for such uses. But doctors are allowed to prescribe drugs off-label where they see fit, and Celexa is the fourth most prescribed medication for pediatric depression.

On January 7, 2004, Forest Laboratories received a wide-ranging request from the New York Attorney General, Eliot Spitzer, asking for information about how the company tested and promoted drugs like its antidepressant Celexa for so-called off-label, or as yet unapproved, uses. Mr. Spitzer's action follows an article in The New York Times which disclosed that Forest did not tell a medical journal about a failed, unpublicized trial of Celexa in children and adolescents when it published an article this month about a positive trial of the same drug in the same types of patients. Some of the article's authors were Forest employees.

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 Celexa and suffered side effects, please fill out the form at the right for a free case evaluation by a qualified drug side effects attorney.