Yourlawyer.com (Prozac News)

Tamoxifen Label May Finally Warn About Antidepressant Risks

Tue, 02 Jun 2009 00:00:00 -0700

A study that we reported on yesterday that showed that use of some antidepressants-namely Paxil, Prozac and Zoloft-may interfere with the efficacy of tamoxifen, leading to recurrence of breast cancer, has the Food & Drug Administration (FDA) planning to warn doctors of potentially adverse interactions. According to Dow Jones News Wire, it will likely add the information on the interactions to tamoxifen's label.

Tamoxifen is used to prevent the return of estrogen-dependent breast tumors. More than 500,000 women in the U.S. are taking tamoxifen and about 30% of those women are also prescribed antidepressants to treat hot flashes, Dow Jones News Wire said.

Hot flashes are a common side effect of tamoxifen therapy. As we reported yesterday, doctors started using antidepressants for hot flashes after hormone-based treatments were linked to the development of breast cancer. However, treating tamoxifen hot flashes with antidepressants is an off-label use of such drugs.

As we reported yesterday, a study conducted by Medco Health Solutions Inc. and presented over the weekend at the American Society of Clinical Oncology's annual meeting, found breast cancer patients who took an antidepressant like Paxil, Prozac or Zoloft with tamoxifen were more than twice as likely to have their cancer return. The study, which involved 1,300 women, found that those who took such drug combos for one year had a breast cancer recurrence rate of 16% compared to a recurrence rate of 7.5% for women not taking the drugs. However, according to Dow Jones News Wire, not all antidepressants had the same impact, and the study showed women on drugs like Celexa, Lexapro and Luvox didn't have a statistically higher rate of cancer recurrence.

According to a report on Bloomberg.com, tamoxifen works by combining with the CYP2D6 enzyme, which is produced by the liver. This produces endoxifen, a substance known to fight tumors. But some antidepressants, including Paxil, Prozac and Zoloft, block the CYP2D6 to varying degrees, which likely impacts the efficacy of tamoxifen.

Prior to the Medco study, lab studies had shown that some antidepressants could impact tamoxifen. As we reported yesterday, the FDA had already taken a look at interactions between tamoxifen and antidepressants. According to Bloomberg.com, the 2006 review concluded that data on the effect should be added to tamoxifen labeling; however, to date, there is no such statement on this risk on the medication’s label.

According to Dow Jones News Wire, Larry Lesko, director of the FDA's Office of Clinical Pharmacology, said now that the FDA has evidence about clinical outcomes as a result of the drug interaction, it will likely add that information to tamoxifen's label.

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.

Paxil, Prozac Linked to Heart Birth Defects

Tue, 25 Nov 2008 00:00:00 -0800

Paxil and Prozac, two popular antidepressants, have been linked to heart birth defects by a new study. According to an article published in the November issue of The British Journal of Clinical Pharmacology, the risk for such birth defects was the highest among Prozac users who also smoked during their pregnancy.

For the study, researchers from Israel, Italy and Germany looked at the pregnancy outcomes of 2,191 women. Of those, 410 had taken Paxil during their pregnancy, while 314 had taken Prozac. The remaining 1,467 had no exposure to either antidepressant.

Among the group taking Prozac, the prevalence of major heart birth defects was 2.8%. It was 2% in the Paxil group and 0.6% in the control group. That means that women who took Prozac during pregnancy were 4.47 times more likely to have a baby with a heart anomaly and women who took Paxil were 2.66 times more likely. There was no increase in other major congenital anomalies, although the study did find that women taking Prozac or Paxil had babies with slightly lower birth rates than those in the control group.

The study also found that women who smoked more than 10 cigarettes a day while taking one of the antidepressants were 5.40 times more likely to have a baby with a heart anomaly. Those smoking less than ten cigarettes a day were 2.75 times more likely to have a baby with a heart birth defect, the study said.

According to the researchers, the risk of heart birth defects was highest among those smokers who took Prozac. “These findings clearly show a significant association between major heart anomalies and taking fluoxetine (Prozac) and smoking during pregnancy,” lead author Professor Asher Ornoy from the Israeli Teratology Information Service in Jerusalem, Israel, told Science Daily.

According to Science Daily, the researchers are urging pregnant women who must use one of the antidepressants to stop smoking if they do so. They also recommended that those taking Prozac be given a fetal echocardiogram in their second trimester to diagnose possible heart anomalies.

Pregnant women taking either drug should speak to their doctors, but they should not stop their medication unless they are told to do so, Science Daily said.

American Children Take the Most Psychotropic Drugs

Fri, 26 Sep 2008 00:00:00 -0700

A new study reports that American children are about three times likelier to be prescribed psychotropic medications than children in Europe. The study states that the differences may be attributable to regulatory practices and cultural beliefs about the role of medication in emotional and behavioral problems.

Julie Zito led the team comprised of researchers from the U.S., Germany, and the Netherlands. The group investigated prescription levels in the three countries. Zito reported that, "Antidepressant and stimulant prevalence were three or more times greater in the U.S. than in the Netherlands and Germany, while antipsychotic prevalence was 1.5 to 2.2 times greater." The use of antidepressants, such as Prozac, and stimulants, such as Ritalin, in children has been the subject of much controversy; this study is believed to quantify the differences in practice between the US and Western Europe.

Study authors believe the differences may be partly due to different diagnostic classification systems. For instance, "The US trend of increasing bipolar diagnosis in children and adolescents does not reflect European practice." The team also discussed government cost restrictions in Europe, the increased amount of child psychiatrists per capita in the U.S., as well as the U.S. practice of using two or more different psychotropic drugs in a single year as possible explanations. "Direct to consumer drug advertising, which is common in the U.S., is also likely to account for some of the differences. The increased use of medication in the US also reflects the individualist and activist therapeutic mentality of US medical culture," Zito added.

Earlier this month we reported about one million children and teenagers are treated for schizophrenia and prescription rates for atypicals—the anti-psychotic drugs most prescribed for these disorders—have increased more than five-fold for children over the past 15 years and are also being used to control outbursts and aggression in children with a wide variety of diagnoses representing about 80 percent of the prescriptions written for maladies such as autism, ADHD, bipolar disorder, depression, and anxiety, despite the drugs’ serious side effects. Some uses are off-label, or not approved by the Food and Drug Administration (FDA). Approximately three million Americans suffer from schizophrenia and about 20 percent begin to show symptoms as children or teens.

Meanwhile, state officials are finding atypical antipsychotics have become the largest drug class in Medicaid and many question if this is due to marketing or need; several states are suing drug makers for off-label promotion and commissioning "ghost-written" articles to increase use. But, drug makers continue to obtain new approvals from the FDA to treat more conditions. In the last two years, Risperdal received approval to treat schizophrenia in adolescents and the irritability of autism in children ages five to 16. Nicola Huff, whose son, John Aaron, took Risperdal for seven years to resolve behavioral problems said at age 14, he developed female-sized breasts that had to be surgically removed. Tammy Wandling, whose son Austin has autism, said a psychiatrist put him on Risperdal at age four. In less than nine months, Austin developed a baseball-size growth in his right breast. Research suggests Risperdal can cause an increase in the hormone prolactin, which causes breasts to enlarge and produce milk.

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.

Prozac, Effexor, Paxil Don't Do Much For Most Patients

Wed, 27 Feb 2008 00:00:00 -0800

Prozac, Effexor, and Paxil may only be effective in the most severely depressed patients. In a recent study conducted by British researchers on the effect of some antidepressants, it seems that antidepressant medications 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. The research was led by Irving Kirsch of the University of Hull and reviewed a series of studies—both published and unpublished—on four specific antidepressants.

The study examined the question of whether a person's response to these anti-depressant medications was dependent on how depressed the patients were before they received treatment for their depression. All four medications studied are the so-called selective serotonin reuptake inhibitors—commonly known as SSRIs—and were specifically Eli Lilly and Company’s Prozac, which is also known as fluoxetine; Wyeth's Effexor, which is also called venlafaxine; GlaxoSmithKline's Paxil, which goes by both Seroxat and paroxetine; and Bristol-Myers Squibb Company’s drug Serzone, which is also called nefazodone. Bristol-Meyer’s Serzone is no longer marketed in the United States.

The research group discovered that when compared with placebo, these new-generation SSRI antidepressant medications did not provide any measurable, clinically significant improvements in depression in those patients who initially suffered from moderate or even very severe depression. The study did reveal, though, that the most significant benefits occurred only in the very severely of depressed patients. "Drug-placebo differences in antidepressant efficacy increase as a function of baseline severity, but are relatively small even for severely depressed patients. The relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication," the researchers wrote.

As part of their study, the researchers also obtained data on all of the clinical trials submitted to the U.S. Food and Drug Administration (FDA) for the licensing of the four antidepressant SSRI drugs. "Although patients get better when they take antidepressants, they also get better when they take a placebo, and the difference in improvement is not very great. This means that depressed people can improve without chemical treatments," Kirsch said in a statement concerning the findings of the study. But, Mary Ann Rhyne, a spokeswoman for Paxil maker GlaxoSmithKline, argued that the study only looked at data submitted prior to the drug's U.S. approval. "The authors have failed to acknowledge the very positive benefit these treatments have provided to patients and their families who are dealing with depression and they are at odds with what has been seen in actual clinical practice," Rhyne said. "This analysis has only examined a small subset of the total data available, while regulatory bodies around the world have conducted extensive reviews and evaluations of all of the data available," she added.

Doug Petkus, a spokesman for Wyeth, the maker of Effexor, said he had not yet seen the recent study and could not comment on its contents.

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.

Drug therapy caused some scary side effects

Tue, 02 May 2006 00:00:00 -0700

Erin Evans is one parent who wishes she had never heard of anti-psychotics.

As a military couple, she and her husband, Joe, moved around frequently. Their son, Rex, 13, was babied a lot. His mother now feels that he was not ready for school when he reached kindergarten age.

He had trouble focusing in the classroom and was diagnosed with attention-deficit disorder at age 6. He started on an ADHD medicine and began hallucinating about worms and bugs in his food.

Soon he was also on Prozac for anxiety, but the nervousness and paranoia persisted.

At age 8, Rex was given Risperdal by a Tennessee child psychiatrist in private practice who consulted for the military. He said the boy probably had obsessive-compulsive disorder, too, Evans says.

"(He) didn't tell us it had never been approved for children or warn us about any side effects," she says.

For the first few weeks, Risperdal helped a little; Rex became less anxious and hyper. "But then it wore right off, so the doctor kept increasing the dose," she says.

After one month on Risperdal, Rex started having tremors; within a few months, his hands shook so severely that he could barely write at school, "and I'd have to guide the cup of milk to his mouth in the morning," Evans says.

But the psychiatrist said the tremors weren't so bad, Evans says, and urged the family to continue the drug.

The psychiatrist didn't pressure them, she says, "but I'm from the generation where, when a doctor says something, you believe it."

Then, about a year after Rex started Risperdal, the Evanses found out that he might have schizoaffective disorder, a psychotic illness that children rarely get. A doctor's report said Rex probably would need to be institutionalized.

That year, when Rex was 9, the family moved to Colorado Springs. The parents started to learn more about Risperdal and, for the first time, they realized that Rex's symptoms could be side effects, so they started to wean him off the drug. In a few weeks they noticed his jaw was scrunching up and his facial expressions were becoming distorted. By then, Evans says, she had read up on tardive dyskinesia (TD), a neurological disorder that can be caused by anti-psychotics.

Rex became less anxious, but the TD worsened. "He had a horrible, ugly look on his face all the time," Evans says. Friends no longer came to play. Rex went from winning an award for best reader in the third grade to claiming he couldn't remember how to spell his own name in fourth grade.

Then in fifth grade, Rex slowly began to improve. A medical exam showed spasms in his thorax, perhaps linked to the upper body spasms, restricting the flow of oxygen to his brain.

He began oxygen therapy, and he quickly became more responsive to others and did better at school, Evans says. He also had behavioral therapies. At the end of elementary school, Rex had episodes only a few times a week.

But junior high has brought more stress and bullying, and the episodes have become more frequent. "His movement-disorder specialist said he expected Rex to have this for the rest of his life," Evans says.

Now she is bitter. "I trusted the doctors, I trusted the FDA ... and I feel betrayed by both," she says.

The Food and Drug Administration "does not regulate the practice of medicine," says Thomas Laughren, head of the division of psychiatry products. He adds that he's concerned about the use of such drugs in kids without systematic safety data.

Nobody knows how many children on atypicals get TD, says Ramy Mahmoud of Janssen LP, maker of Risperdal, but it's rare in adults. "Our drug isn't indicated for children," he says. "It's a strong drug. It has risks and benefits. Doctors and patients together have to weigh the benefits, at the start and on a continuing basis, along with the harm and suffering."

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.

ADD Drug Strattera, Already Under FDA Scrutiny, Raising New Safety Concerns in UK as Well

Tue, 21 Feb 2006 00:00:00 -0800

Although pharmaceutical giant Eli Lilly (Lilly) continues to maintain that its attention deficit drug, Strattera, is safe, the company’s actions as well as those of the FDA would seem to indicate quite the opposite.

On September 28, 2005 for example, Lilly declared it was adding a black-box warning to Strattera. That warning advises that the drug may increase suicidal thoughts among youths.

FDA officials said Eli Lilly must also create a medication guide for patients and healthcare providers pertaining to the new black box warning. Black box warnings are the most prominent and serious of medication warnings.

The FDA said Lilly submitted results from a Strattera clinical trial of 1,357 youths taking the medication that found five of them had increased suicidal thoughts, while none of 851 youths taking a placebo showed such changes. Lilly said one youth attempted suicide during its Strattera trials, but that researchers saw no signs of increased suicidal thoughts among adults.

Strattera has also been linked to liver problems. In 2004, Lilly warned doctors to stop prescribing Strattera in patients with jaundice or who show signs of liver damage.

Lilly warned that Strattera can cause severe drug related liver injury that can progress to acute liver failure resulting in death or the need for a liver transplant. In December 2004 the FDA updated Strattera's label to include the serious liver side effects.

In December of last year, Dr. Thomas Laughren, director of the FDA's division of psychiatry products, said the federal government requested Lilly to assess 13 clinical trials conducted on children to measure a suicide risk.

"The risk for any individual patient taking this drug is quite low, but from a public health standpoint, four (case) per thousand is a fairly big signal, given there are tens of thousands of patients taking this drug," Laughren said.

In June 2005, the FDA announced it will be investigating all attention deficit hyperactivity disorder drugs including Strattera, Ritalin, Concerta, and Adderall in response to reports of serious psychiatric side effects in patients taking Concerta and Ritalin. Some ADHD drugs are also associated with cardiovascular side effects.

In what many experts are viewing as an unusual turn of events, an FDA advisory panel, in January of this year, voted (8-7-1) to recommend that the agency order the inclusion of the most serious “black box” warning on all stimulant ADHD medications due to evidence of a potential risk of heart attacks, strokes, and sudden death. The drugs include amphetamines, such as Adderall, and methylphenidates, sold as Ritalin, Concerta, Methylin, and Metadate.

The panel also voted 15-0-1 to recommend that the FDA require that the drugs include a medication guide for patients and parents.
This new controversy was prompted by data that showed that widely prescribed ADHD drugs like Ritalin may be lined to as many as 25 deaths that occurred between 1999 and 2003. Of these deaths, 19 involved children.

In addition, the FDA was advised of 54 cases involving serious cardiovascular problems like heart attacks, strokes, hypertension, heart palpitations and arrhythmias in both adults and children taking these medications.

There is also the open issue of another 26 deaths between 1969 and 2003 in medicated ADHD patients involving suicide, intentional overdose, drowning, heat stroke, and underlying diseases.

The panel’s vote also caught the FDA off guard because the committee was convened to advise the agency on how to design studies to assess possible risks associated with stimulant ADHD medications. (Adderall is the only non-stimulant ADD drug).

During the meeting, however, talk soon turned to the over-prescribing of these drugs and the public as well as many doctors were unaware of these serious potential risks. The panel then agreed to consider the enhanced-warning issue that was outside of its planned agenda.
The FDA has attempted to back off from the unexpected action by the panel by issuing a statement that it would be reluctant to require a black box warning based on a “theoretical risk.”

Such warnings could unreasonably deter patients and doctors from using a drug that could benefit them, said Robert Temple, MD, director of medical policy at the FDA's Center for Drug Evaluation and Research. He stated: "The absence of bona fide problems in your hand pushes against the box. We will also, frankly, worry about the possibility that overstatement can do active harm."

Thus, Temple indicated the full FDA would wait for the recommendation of a pediatric advisory committee scheduled for March before reaching any decision with respect to new warnings. That panel, which is made up of pediatricians and psychiatrists, is considered more likely to look favorably on the benefits of ADHD drug treatment as outweighing the potential risks.

Now comes word that Strattera is faring no better in the UK in light of these safety concerns well as the possibility that the drug is also associated with seizures and a potentially dangerous lengthening of the interval between heartbeats.

According to IndyStar.com, the Tacoma (Washington) News Tribune, and Reuters, the “warnings are based on an internal report by the British Medicine and Healthcare Products Regulatory Agency. The report, which has not been made readily available to the public, was obtained by The News Tribune after a Swedish court ordered it released in that country.

“Though the number of seizures and heart-rhythm problems is small, the British agency said problems could be under-reported, and it warned doctors and consumers that the drug should be used with caution in people prone to such problems.

“In particular, they warned about potential heart problems when Strattera is combined with antidepressants like Paxil and Prozac.”
Although British authorities still believe the drug’s benefits outweigh its risks, they are updating the drug's label in that country to warn of the possible problems. Presently, no warnings regarding the seizure risk are contained in the U.S. labeling. The heart problem risk, however, was inserted in the 25-page U.S. label in January at the request of the FDA.

Studies Assess Mix of Antidepressants, Pregnancy

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

Three studies published over the past week have sparked new concerns about the health risks of taking and not taking antidepressants during pregnancy. Two of the studies point to possible dangers to the fetus, and in response to the latest study, released Wednesday by the New England Journal of Medicine, the Food and Drug Administration announced it was considering tougher warnings on the drugs' use.

Separate research, published last week in the Journal of the American Medical Assn., shows that mothers who stop taking the drugs run a high chance of slipping back into debilitating depression.

Taken together, the studies represent an increasingly difficult conundrum for mothers and doctors.

"These data make me feel all the more cautious about using antidepressants in pregnancy," said Dr. Victoria Hendrick, a professor of psychiatry at UCLA. "But it's still something I'm going to do because I see very, very depressed women."

Prozac and other antidepressants known as Selective Serotonin Reuptake Inhibitors enhance the action of the brain chemical serotonin.

Since being introduced in the late 1980s, the drugs have become the standard treatment for depression.

The range of effects of manipulating serotonin levels is not well understood. For example, serotonin can cause blood vessels to constrict. It also serves as a growth factor, helping organize neural circuitry in a maturing brain.

The FDA has begun to strengthen warnings concerning the use of the drugs by pregnant women. In December, the agency ordered a new warning label for paroxetine, sold under the brand name Paxil, after two studies linked it to heart defects in newborns.

The agency's new concern involves a lung problem known as persistent pulmonary hypertension, which normally occurs in 1 in 1,000 births.

The researchers found six times that risk in infants born to women on antidepressants.

The team interviewed 377 mothers of babies born with the condition, and found that 14 had taken antidepressants in the second half of pregnancy. In a control group of 836 mothers with healthy children, six had taken the drugs, according to the study in the New England Journal of Medicine.

The lung ailment leads to inadequate oxygen levels in the blood. Most babies recover. In severe cases it can cause deafness, neurological problems or death.

"We find the association they have reported with this very serious condition to be very worrisome," said Dr. Sandra Kweder, deputy director of the FDA's Office of New Drugs.

Christina Chambers, an epidemiologist at UC San Diego who led the research, cautioned that "even with a sixfold increase, you're still talking about a fairly low risk."

On Tuesday, a study published in the Archives of Pediatric and Adolescent Medicine bolstered previous reports that babies born to mothers on antidepressants could suffer signs of withdrawal from the drugs in the first few days of life.

Nearly a third of 60 newborns exposed to the drugs as fetuses experienced symptoms that included tremors, gastrointestinal problems and sleep disturbance, according to the study.

Two of the infants in the study suffered seizures. In most cases, the symptoms peaked in two days and then began subsiding.

When the researchers reviewed 37 cases of women taking paroxetine, they found that the symptoms did not occur at low doses.

The risks and the unknowns make it tempting for women to give up antidepressants for nine months.

The odds are against them. Researchers, led by Dr. Lee S. Cohen of Harvard Medical School, tracked 201 women who were taking antidepressants around the time they became pregnant. Sixty-eight percent of those who discontinued the medications relapsed into depression, compared with 26% of those who kept taking the drugs.

There are few studies on how a mother's depression, left untreated, affects the health of her fetus.

"These depressed women might not be eating right," Hendrick said. "They might be losing weight. Women might be suicidal. They might be more prone to smoking and drinking."

The use of antidepressants by women who are pregnant is widespread, since depression during pregnancy is fairly common. Nonetheless, it's not clear how many infants have been exposed.

The FDA said Wednesday that more research needed to be done.

The long-term effects of fetal exposure to antidepressants are particularly hard to determine. Research could require following children for a decade or more.

"There are not a lot of studies that look at these children five or 10 years down the line," said Dr. James Mills, an epidemiologist at the National Institute of Child Health and Human Development.

In recent years, the FDA has been criticized for being slow to react to evidence that the drugs can increase suicidal thoughts in some children and teenagers.

In 2004, the agency forced drug makers to include a strong warning of such risks in the information for their products.

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.

Antidepressants May Harm Newborns' Lungs

Wed, 08 Feb 2006 00:00:00 -0800

New research has linked the use of Prozac and other similar antidepressants during pregnancy to yet another complication in newborns: an uncommon but life-threatening lung problem.

Infants whose mothers took the antidepressants in the second half of pregnancy had six times the expected risk of developing the lung disorder, the researchers reported in Thursday's New England Journal of Medicine.

The antidepressants implicated are called selective serotonin reuptake inhibitors, or SSRIs, a class of drugs that includes Prozac, Paxil and Zoloft.

"This is the latest in a series of troubling reports of possible adverse effects of SSRIs on the fetus," Dr. James L. Mills of the National Institute of Child Health and Human Development wrote in an accompanying editorial.

Other research has linked use of the antidepressants late in pregnancy to jitteriness, irritability, low blood sugar and difficulty breathing in newborns. The Food and Drug Administration warned last year that Paxil may be associated with heart defects when taken during the first three months of pregnancy.

For ethical reasons, medications cannot be tested on pregnant women, and the possible effects of a drug on a fetus can only be observed after the medicine is on the market and in use.

One of the researchers, Christina Chambers of the University of California at San Diego, said of the findings, "If it's a true risk, it's very low." According to the researchers' calculations, 99 percent of women who took the antidepressants late in pregnancy would deliver a child without the problem.

Dr. Sandra Kweder, deputy director of the Food and Drug Administration's Office of New Drugs, called the results worrisome and said the agency would be issuing a public health advisory in a few days.

"I would emphasize that this isn't a cause for panic among women who are taking these medications," Kweder said.

Women should not stop taking the antidepressants on their own and should check with their doctors if they have concerns, Kweder said. "For many women, the small risk suggested by this study may be outweighed by their own personal need for treatment of a mental health condition," she said.

In the study, researchers looked at a problem called persistent pulmonary hypertension. The disorder develops after birth when the infant's lungs do not quickly adapt and there is not enough oxygen reaching the blood. It occurs in one or two infants per 1,000 births.

The researchers interviewed the mothers of 377 infants who had the problem and asked them if they had taken any medication for depression while pregnant. The women were compared with the mothers of 836 healthy babies born about the same time.

Fourteen mothers whose infants had the complication reported taking SSRIs during the second half of their pregnancy, compared with six mothers in the comparison group. The researchers calculated the antidepressants increased the risk of the disorder six-fold.

They found no increased risk of the lung problem from SSRI use during the first half of pregnancy or from the use of other antidepressants during pregnancy.

Chambers and some of the other researchers have received research support from drug makers.

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.

Depression Drugs 'Can Raise Birth Defect Risk'

Thu, 01 Sep 2005 00:00:00 -0700

Babies born to women taking common anti-depressants during pregnancy are substantially more likely to suffer birth defects and to be born prematurely, according to research.

A study of more than 1,000 expectant mothers found use of selective serotonin reuptake inhibitors (SSRIs), including Prozac and Seroxat, during the first three months of pregnancy was associated with a 40 per cent increase in the risk of congenital defects.

Danish researchers said the study suggested use of the drugs by pregnant women led to a 60 per cent greater chance of heart defects in their babies and a 40 per cent greater likelihood of a premature birth.

Prescriptions for SSRIs jumped from seven million in 1997 to 19 million in 2003. They are thought to be used by 3.5 million people in England.

The study's results were presented at last week's International Society for Pharmacoepidemiology conference in Nashville, and will be published today in Pulse, the weekly newspaper for GPs.

The researchers stressed their results were only initial findings and that there was a possibility they could be linked to the depression of the mother rather than the drugs.

Dr Pia Wogelius, the study's lead author, of Aalborg Hospital in Denmark, said: "We found an association between maternal use of SSRIs and an increased risk of both congenital malformations overall and congenital cardiac malformations.

"Moreover, maternal use of SSRIs any time during pregnancy was associated with an increased risk of preterm birth. It is unclear whether the effects were causal or due to other factors related to the underlying disease."

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 Launches Site to Warn Patients, Doctors of Drug Risks

Fri, 20 May 2005 00:00:00 -0700

The U.S. Food and Drug Administration has begun issuing alerts to patients and doctors on its Web site about emerging drug-safety concerns, including dangers posed by drugs prescribed for unapproved purposes.

The new site, called Drug Watch, marks a significant change in how the agency communicates risks to the public. In the past, the FDA has spent months or years privately weighing and debating risk information with drug companies until a final determination was made on the scientific significance of the danger.

After being bashed by Congress and consumers for its slow response to emerging information about heart risks posed by blockbuster pain medications such as Vioxx, the FDA now is beginning to make risk information available to the public much sooner.

"This is really a fundamental change," said Dr. Steven Galson, the acting director of the FDA's Center for Drug Evaluation and Research. "We do intend to give companies a heads up before posting something new about their drugs, but we're not going to discuss it with them. They're not going to review it."

The safety alerts posted so far on the site http://www.fda.gov/cder/drugSafety.htm are notable also because they emphasize risks posed by doctors prescribing drugs for purposes never approved by the FDA. It's a practice called "off-label prescribing" because it involves using drugs in ways and to treat conditions not covered by the safety and effectiveness determinations on their FDA-approved labels.

"That's a very important aspect of this," Galson said. "As you know, we don't regulate the practice of medicine. We have no way of preventing physicians from using drugs off label."

But Galson said the agency does have a responsibility to let people know about known risks of off-label uses. "This is very controversial, of course," he said.

Some off-label drug uses are beneficial and based on good science, others have little proof of effectiveness and still others have been proved worthless in studies.

Officials at the American Medical Association, which represents doctors, and the Pharmaceutical Research and Manufacturers of America, which represents drugmakers, declined to comment, saying they are evaluating the Drug Watch site and will submit formal comments to the FDA.

Ed Sagebiel, a spokesman for Indianapolis-based drugmaker Eli Lilly, said the company generally supports the FDA's new effort. The site includes alerts for Eli Lilly drugs Prozac, warning of suicide risks related to it and other antidepressants, and Zyprexa, warning of an increased risk of death when it and other atypical antipsychotics are prescribed off-label to treat dementia in elderly patients.

"We just want, from our standpoint, to properly balance warning people and patients of safety concerns without frightening them or inadvertently making them stop taking their medicines," Sagebiel said.

Galson said others in the drug industry have expressed similar concerns. "They're worried we may be over-warning and dissuading patients from using products that may do good," he said. "We expected we would get that sort of push-back."

Advocates for patients called the site an incremental move in the right direction, even though it requires patients to seek out the information on the Internet, rather than it being given to them when they pick up their medicines. The emphasis on early and off-label risk information is a departure for the FDA, they said.

"I don't think they had the political courage even a few years ago to take these kinds of steps," said Larry Sasich, a pharmacist with Public Citizen's Health Research Group, a consumer watchdog that publishes a searchable database of drug risks at www.worstpills.org.

Sasich said he thinks the FDA is realizing that the only way to change risky prescribing is for consumers to know more about the drugs they take. Changing the official labeling on drugs and sending letters to doctors about new risks hasn't worked, he said.

Sasich expressed concern that elderly patients who are the biggest consumers of prescription drugs won't have enough access to Drug Watch information that's available only on the Web.

Cynthia Pearson, the executive director of the National Women's Health Network in Washington, praised the direct communication of risks listed atop several drugs on the site.

"Our position always has been: Get people access to good information and they can make good decisions," Pearson said.

The Drug Watch site, still being developed, lists information on about 200 drugs. Most of them include routine prescribing information. Among those tagged with an "FDA Alert:"

Accutane, a drug for severe acne. "The FDA continues to assess reports of suicide or suicide attempts" associated with this drug. All patients "should be observed closely for symptoms of depression or suicidal thoughts," the alert warns.

Cytotec, also called misoprostol, a drug approved to prevent ulcers. The alert warns of risks in its off-label use in labor and delivery. "These uses are not approved by the FDA. No company has sent the FDA scientific proof that (Cytotec) is safe and effective for these uses. There can be serious side effects, including a torn uterus..." the alert warns.

Zyprexa, Risperdal and several other psychiatric drugs called atypical antipsychotics. The FDA warns that when prescribed off label as a treatment for dementia, older patients "had a higher chance for death than patients who did not take the medicine."

Amiodarone, marketed also as Cordarone and Pacerone, a popular heart drug approved only to treat a specific life-threatening rhythm disorder. It is widely prescribed off label for non-life-threatening atrial fibrillation. The alert warns of potentially fatal side effects including lung toxicity, liver injury and worsened heart rhythm problems.

Gabitril, a drug approved to treat seizures. The alert warns that it risks causing seizures when used off label. Gabitril's "safety and effectiveness have not been established for any other use," the alert notes, adding that the drug's maker, Cephalon, will be educating doctors "to discourage off-label use."

Sheryl Williams, a Cephalon spokeswoman, said through Drug Watch, the FDA appears to be trying to do a better job of communicating and addressing the increasing prevalence of off-label prescribing.

A Knight Ridder investigation published in 2003 found that patients are being injured and killed when doctors routinely prescribe medications in ways that the FDA has never approved as safe and effective. Off-label prescriptions for top-selling drugs accounted for nearly a quarter of their retail sales.

Williams said most of the prescriptions that doctors write for Gabitril are to treat psychiatric conditions - not epileptic seizures. Bipolar disorder is a particularly popular use, she said.

"The problem is there is no guidance for them to do so. We haven't done double-blind studies. We haven't even done single-blind studies," Williams said. "Our scientific team doesn't believe there is sufficient evidence that a drug like Gabitril would be effective in bipolar disorder."

While Gabitril is effective in reducing the frequency of seizures in people with epilepsy, she said, when used off label the drug has been associated with seizures in people without epilepsy.

Antidepressants Can Affect Newborns

Tue, 17 May 2005 00:00:00 -0700

Women who take Prozac or certain other antidepressants late in pregnancy raise the risk that their babies will suffer jitteriness, irritability and serious respiratory problems during their first couple of weeks, researchers say.

Babies born to women taking antidepressants in the last three months of pregnancy were three times more likely to develop drug-related symptoms than those born to women who did not use the drugs or took them only in early pregnancy, according to a University of Pittsburgh study that pooled previous research.

The study was published in Wednesday's
Journal of the American Medical Association.

Most of the symptoms are mild and usually disappear after about two weeks, but some require intensive care hospitalization, the researchers said.

The drugs involved include Prozac, Paxil and other antidepressants known as selective serotonin reuptake inhibitors or SSRIs, and also serotonin norepinephrine reuptake inhibitors, which include Effexor.

At least 80,000 U.S. women yearly take the drugs during pregnancy, the researchers estimated.

Serious respiratory problems develop in perhaps one out of 100 infants born to these women, said Dr. Eydie Moses-Kolko, a psychiatrist who led the study.

The Food and Drug Administration and drug makers recently agreed to labeling changes on these drugs to include information about the symptoms, which some doctors call neonatal behavioral syndrome, or withdrawal syndrome.

Moses-Kolko said there has been little research on whether the drugs have any lasting effects in children, although one study found that affected newborns were developmentally normal at 8 months.

"I don't think this is cause for alarm," but patients and doctors should be aware of the risk, she said.

Women should talk to their doctors about reducing use of the drugs late in pregnancy but should also be aware that the risks of major depression might outweigh the short-term problems the drugs might cause in newborns, she said.

How Lilly Gilded Prozac's Profile

Tue, 10 May 2005 00:00:00 -0700

This spring, Jeff Weise shot himself dead after taking the popular antidepressant Prozac.

He scored national headlines because he took nine innocent people down with him in the worst school shooting rampage since Columbine. Some now wonder whether Weise's antidepressant rather than depression itself may have finally pushed the troubled teenager over the edge. After all, unstable Prozac users have been pulling the trigger for years.

Joseph Wesbecker killed himself and eight others while taking Prozac back in the late 1980s, when the still-new drug was viewed as a miracle cure for depression. Relatives of the survivors blamed Prozac and sued its maker, Eli Lilly (LLY:NYSE) , for damages. That case, which ended in a settlement, began to expose serious problems with drug research that have grown even more obvious over time.

By now, internal documents have surfaced highlighting concerns about drugs like Prozac known as selective serotonin reuptake inhibitors, or SSRIs that date back to their early clinical trials. Worried health care experts have long attempted to make this evidence known, but they have found themselves drowned out, and even attacked, by powerful scientists with close ties to the drug industry.

In this second installment of a five-part series examining conflicts in the drug industry, TheStreet.com examines how big pharmaceutical companies heavy on marketing know-how but increasingly strapped for big-selling new drugs pressed the popular antidepressants into service in spite of lingering questions over their safety.

The drug companies continue to stand behind their blockbuster antidepressants and market them to the masses. And they keep raking in billions of dollars in profits more than any other industry as a result of their success.

But prestigious medical journals, including those that regularly publish research by the well-connected scientists, have called for ethical reforms. So have consumer watchdog groups. Industry critics insist that drugmakers exert too much influence over researchers, consumer groups and even the government agency charged with regulating them.

As a result, the big pharmaceutical houses' reputations and their share prices have begun to take a hit. Shares of Eli Lilly, which now has two major antidepressants on the market, have lost a quarter of their value over the past year. Shares of Pfizer (PFE:NYSE) , which makes bestseller Zoloft, have fallen by a similar amount.

Early Warnings

David Healy, a noted British psychiatrist and author of Let Them Eat Prozac, has taken aim at Prozac and its competitors alike.

"I happen to believe that Prozac and other SSRIs can lead to suicide," Healy said at a 2000 university conference that would go on to spark a huge controversy. "These drugs may have been responsible for one death for every day that Prozac has been on the market in North America. In all likelihood, many of you will not agree with me on this [but] you haven't seen the information that I have seen."

Eli Lilly was quick to defend its own drug.

"While reasonable physicians may differ in their opinions of the safety and effectiveness of a given medication or even a class of medications the fact is that Prozac has been approved for use by medical regulatory agencies in 120 countries worldwide," the company told TheStreet.com. "Additionally, Prozac has been credited by millions of patients and their families with improving their lives. These facts speak to the overall safety of the product."

But clinical trial data, normally unavailable to the general public, has come to light, exposing serious problems with the drugs. In one drug trial, documents obtained by CNN show, some 3.7% of Prozac users attempted to commit suicide. The same study shows that less than 1% of participants on non-SSRI depressants engaged in the same behavior.

Trials of Zoloft have raised questions about the effectiveness of SSRIs as well. In a 1991 letter prior to the drug's approval, the Food and Drug Administration noted that two separate studies had shown Zoloft to be no more effective than placebo. The agency admitted that the evidence supporting Zoloft was "not as consistent or robust as one might prefer it to be." But it went on to say that such facts were "insufficient to undermine" approval of the drug.

Still, Pfizer itself was apparently worried.

"Pfizer's depression program has in fact demonstrated a roughly 50% failure to demonstrate efficacy in clinical trials, a great number of which remain unpublished," Healy wrote in a letter last summer to the FDA. "So poor were the results from the early trials that they raised concerns that this drug might not get through the regulatory authorities."

Not only did Zoloft often prove ineffective, Healy said, but the drug like other SSRIs seemed to heighten suicide risks as well. On multiple occasions, he said, clinical investigators linked Zoloft to suicidal tendencies.

"The evidence that Zoloft works is, in many respects, less strong than the evidence it causes suicidal behaviors," Healy concluded.

Pfizer didn't answer questions about the drug for this story.

To be sure, Healy has taken plenty of heat for his views. Most notably, he lost out on a prestigious job at the University of Toronto shortly after his controversial presentation in 2000. The university, which operates a big mental health center funded in part by the maker of Prozac, abruptly withdrew its offer to Healy because it no longer felt his approach was "compatible with the goals for development of the academic and clinical resource" at the school. Even now, Healy told the FDA, at least one public relations firm working for an SSRI maker specifically lists him as a "problem to be managed."

Power Plays

Healy points to Charles Nemeroff, a psychiatrist with numerous industry ties, as an especially fierce foe. Others have found reason to single out Nemeroff as well. Nemeroff himself failed to return a phone call from TheStreet.com.

"Dr. Charles B. Nemeroff may hold some sort of record among academic clinicians for the most conflicts of interest," the Washington Monthly wrote last year. "A psychiatrist, a prominent researcher and chairman of the department of psychiatry and behavioral science at Emory University in Atlanta, Nemeroff receives funding for his academic research from Eli Lilly, AstraZeneca, Pfizer, Wyeth indeed from virtually every pharmaceutical house that manufacturers a drug to treat mental illness.

He also serves as a consultant to drug and biotech companies, owns their stocks and is a member of several speakers' bureaus delivering talks for a fee to other physicians on behalf of the companies' products."

A recent U.K. investigation, reported by TheStreet.com Monday, raised serious concerns about so-called key opinion leaders with financial ties to the drug industry. The study suggested that drugmakers exercise far too much influence over those who go on to promote their products.

Among those being tainted, it included organizations that portray themselves as consumer groups but are financed by the drug industry. Healy personally warned about the groups in his conference presentation years ago.

"Part of the market development plans for many drugs these days includes the creation of patient groups to lobby on behalf of a new treatment," he said back then. "The most vigorous and hostile patient groups of the anti-psychiatry period have been penetrated by the pharmaceutical industry. (And) other patient groups have been set up de novo by companies."

Others have highlighted major industry problems as well. In 1999, for example, the prestigious Journal of the American Medical Association called for "fair conduct and fair reporting of clinical trials." By then, the New England Journal of Medicine yet another influential publication had already laid out the need for protecting those who do come forth with negative study results. More recently, American Psychologist has specifically suggested "building a firewall between marketing and science" in the mental health field where SSRIs are so used.

David Antonuccio, a medical researcher who penned the third article, is hoping that psychologists faced with prescribing powers in the future will do a decent job of policing themselves. After studying past actions by federal regulators, he seems to have little faith in the FDA at all.

"At 55% of the meetings, half or more of the FDA advisers had financial conflicts of interest," he wrote. "Although federal law generally prohibits the use of experts with financial conflicts of interest, the FDA waived this restriction more than 800 times" in less than three years.
Sleepy Watchdog

Sen. Charles Grassley, a powerful Republican from Ohio, has challenged the FDA's handling of SSRI issues in particular. Just after a major FDA hearing last year, Grassley launched an investigation of the agency for allegedly concealing risks associated with the drugs.

Healy, on his own, volunteered some details about the matter when submitting testimony for the recent U.K. investigation. Ten days before the FDA hearing, he said, three noted psychiatrists who authored most of the trial literature on SSRIs came forth and declared that the drugs were "safe and effective and well-tolerated by children," even though they had never seen the raw data on which their findings were supposedly based. But despite this "pre-emptive strike," Healy noted, the FDA did go on to demand stronger warning labels for childhood use of the drugs.

By then, however, the drugs had already soared in popularity. A government study published last year showed that children who visited the doctor for depression symptoms were nearly three times as likely to wind up on prescription drugs (usually the newer SSRIs) than they were a decade ago. Moreover, it indicated that adults including 13% of women aged 45 to 64 were turning to the drugs as well.

Healy has pointed to drugmakers, which spend far more promoting their products than they do developing them, as the drivers behind that trend.

"Corporations work out what they have to sell and then prepare the market so that we will want those products," he warned years ago. "It works for cars, oil and everything else. Why would it not work for psychiatry?"

Study Ties Antidepressants To Suicide

Mon, 21 Feb 2005 00:00:00 -0800

Adults taking popular antidepressants such as Prozac, Paxil and Zoloft are more than twice as likely to attempt suicide as patients given placebos, according to an analysis of hundreds of clinical trials involving tens of thousands of patients.

The results, published last week in the British Medical Journal, mirror a recent finding of the Food and Drug Administration that the drugs increase suicidal thoughts and behavior among some children and offer support to concerns going back 15 years that the mood-lifting pills have a dark side.

The examination of 702 controlled clinical trials involving 87,650 patients is the most comprehensive look at the subject and is particularly telling because it counted suicide attempts and included patients treated for a variety of conditions, including sexual dysfunction, bulimia, panic disorder and depression.

Experts cautioned, however, that the risks should be balanced against the drugs' benefits. They have been shown to be effective against depression and a host of other disorders in adults, a positive track record largely missing in tests of the drugs on children.

The new study is certain to add to the controversy over the class of drugs known as selective serotonin reuptake inhibitors, or SSRI's.

Since the arrival of Prozac in 1988, these drugs have transformed psychiatry in the United States, even as persistent critics have warned that their benefits were hyped and their risks ignored. A spate of lawsuits in recent years have claimed that the drugs were responsible for violent and suicidal behavior.

New analyses of clinical trials in children last year prompted the FDA to require a prominent black box warning on labels, saying that the medications could increase the risk of suicide. The warning refers only to children but is given to all patients.

American psychiatrists continue to strongly back SSRI drugs. Groups such as the American Psychiatric Association say that fears of drug-induced suicide are vastly exaggerated and that untreated depression carries a far greater risk of suicide.

FDA officials have said they are conducting an independent analysis.

Drugs Raise Risk of Suicide

Fri, 18 Feb 2005 00:00:00 -0800

Adults taking popular antidepressants such as Prozac, Paxil and Zoloft are more than twice as likely to attempt suicide as patients given sugar pills, according to an analysis released yesterday of hundreds of clinical trials involving tens of thousands of patients.

The results mirror a recent finding of the Food and Drug Administration that the drugs increase suicidal thoughts and behavior among some children, and offer tangible support to concerns going back 15 years that the mood-lifting pills have a dark side.

The examination of 702 controlled clinical trials involving 87,650 patients is the most comprehensive look at the subject and is particularly telling because it counted suicide attempts and included patients treated for a variety of conditions, including sexual dysfunction, bulimia, panic disorder and depression.

Experts cautioned, however, that the risks should be balanced against the drugs' benefits. They have been shown to be effective against depression and a host of other disorders in adults, a positive track record largely missing in tests of the drugs on children.

Adults with severe depression should continue to be considered for drug treatment, but those with milder symptoms should probably not be medicated, said John Geddes, a professor of epidemiological psychiatry at Oxford University, who wrote a commentary accompanying the studies.

"For a lot of time, these drugs were seen as a panacea for low mood in general," he said in a telephone interview. "We do need to ensure they are only prescribed for patients with clearly diagnosed depressive disorders."

The new study is certain to add to the controversy over the class of drugs known as selective serotonin reuptake inhibitors, or SSRI's. After the arrival of Prozac in 1988, these drugs have transformed psychiatry in the United States, even as persistent critics have warned that their benefits were hyped and their risks ignored. A spate of lawsuits in recent years have claimed that the drugs were responsible for violent and suicidal behavior.

New analyses of clinical trials in children last year prompted FDA to require a prominent black-box warning on labels that the medications could increase the risk of suicide. The warning refers only to children but is given to all patients.

American psychiatrists continue to strongly back SSRI drugs. Groups such as the American Psychiatric Association say that fears of drug-induced suicide are vastly exaggerated and that untreated depression carries a far greater risk of suicide.

"If these medications were really increasing the incidence of suicide attempts, you would think we would be seeing more completed suicides," said David Fassler, an APA trustee and psychiatrist in Burlington, Vt. "In fact, we are seeing exactly the opposite."

Adolescent suicide rates have dropped 25 percent since the early 1990s, even as more than a million children were put on the drugs, Fassler said. Although no one can say for sure what the connection is between those two trends, Fassler said, "if the medications were significantly increasing the risk of suicide, it is unlikely we would be seeing this kind of decline over time."

The new analysis seems likely to deepen transatlantic divisions over how the drugs are perceived and prescribed: British authorities last year recommended that depressed patients who were able function at home and work should not be medicated right away, but should be counseled to try exercise, self-help, talk therapy or watchful waiting.

David Healy, a psychiatrist at the University of Wales who helped conduct the new study, said managed-care insurance companies in the United States were not likely to look kindly upon physicians who monitor patients without prescribing drugs.

Healy prescribes the drugs but has long raised red flags about them. He asked yesterday why scientists at the FDA and research universities had not previously conducted this analysis, given that the data have long been available.

"For whatever reason, an awful lot of people didn't want to think there was a risk," he said.

FDA officials have said they are conducting an independent analysis.

The new study was conducted by epidemiologist Dean Fergusson and his colleagues at the Ottawa Health Research Institute and included scientists from McGill University. It is published in the current issue of the British Medical Journal along with two related articles and a commentary by Geddes and University of Verona psychiatrists Andrea Cipriani and Corrado Barbui.

Scientists have long bemoaned the lack of high-quality studies on antidepressants and the risk of suicide. One of the new studies, by University of Bristol and University of London researchers, examined drug trials submitted by pharmaceutical companies to British regulators. It found some evidence of self-harm among patients taking antidepressants but was inconclusive as to whether the drugs increased the risk of completed suicides.

A third study found no difference in suicide risk between SSRI drugs and an earlier class of medications known as tricyclic antidepressants.

Complicating the picture is the fact that suicide is rare meaning that it takes very large studies to yield definitive results. Fergusson's meta-analysis pooled data from a large number of studies in the same manner as the recent FDA analysis involving children's trials.

The American Psychiatric Association's Fassler said such an approach could miscount the number of attempted suicides. He said depressed patients who were getting better as a result of medication might be more likely to tell doctors about a suicide attempt, thereby muddying the data.

While Fergusson agreed that better trials are needed, he said he was confident about the results of this analysis, because it relied on placebo-controlled trials considered the most definitive. And not all the patients getting drugs were being treated for depression, he said there was evidence of increased risk of suicide attempts for patients with all kinds of disorders.

Suicide "is uncommon but serious," Fergusson said in an interview. "The biggest concern is these drugs are widely prescribed. There are millions of people on the drugs, so even a risk of one in a 1,000 when you amplify it to the millions, it becomes a public health issue."

FDA Approves Antidepressant Warning Language

Fri, 14 Jan 2005 00:00:00 -0800

In a long-awaited move, the Food and Drug Administration has approved the language for so-called black-box warnings on antidepressants, an agency spokeswoman said late yesterday.

The action comes four months after a government panel determined the medicines were linked to suicide in youngsters. As a result, the panel recommended drug makers add the warnings in order to alert doctors to the serious side effects.

The recommendation followed 18 months of controversy over the medicines. The episode cast a harsh spotlight on the pharmaceutical industry after it became known that some drug makers failed to disclose links between their antidepressants and suicide.

A black-box warning is the most severe warning that can be issued about a prescription drug. The information is prominently placed on package inserts and in physician reference manuals that are read by doctors nationwide.

The warning will be added to several widely prescribed drugs, including Effexor, Zoloft, Paxil and Prozac. Only Prozac was approved for children, but doctors are free to prescribe any medication for patients, which explained widespread usage of many pills.

In a letter to drug makers, the FDA wrote that final labeling should be on company Web sites within two weeks and on all products within 30 days, according to the Pink Sheet, an industry publication. A medication guide is also supposed to be available by Jan. 31.

Doug Petkus, a spokesman for Wyeth, said the Madison-based drug maker, which sells Effexor, will "move as quickly as possible" to add the black-box warnings, although he couldn't provide a specific date.

Last month, some consumer advocates began complaining the FDA was taking too long to enforce the labeling change. They worried some doctors may not change prescribing habits until warnings were issued.

FDA officials said the lengthy process was not unusual, given the need for time-consuming reviews and discussions between agency officials and drug makers. Last month, they said the black-box warning should be in place by late January.

But yesterday, one advocate said the black-box warning was long overdue and continued to criticize the FDA for not acting sooner.

"It shouldn't take this long to issue a warning involving children," Vera Sharav of the Alliance of Human Research Protection said.

Document May Reveal Prozac Risk

Tue, 04 Jan 2005 00:00:00 -0800

An internal document purportedly from Eli Lilly and Co. appears to show that the drug manufacturer had data more than 15 years ago showing that patients on its antidepressant Prozac were far more likely to attempt suicide and show hostility than patients on other antidepressants.

The document also suggests that the company attempted to minimize public awareness of the side effects.

The document, made public Monday, was provided to CNN by the office of Rep. Maurice Hinchey, D-N.Y., who has called for tightening FDA regulations on drug safety.

"The case demonstrates the need for Congress to mandate the complete disclosure of all clinical studies for FDA-approved drugs so that patients and their doctors, not the drug companies, decide whether the benefits of taking a certain medicine outweigh the risks," he said.

The 1988 document indicated that 3.7 percent of patients attempted suicide while on the blockbuster drug, a rate more than 12 times that cited for any of four other commonly used antidepressants.

The document, which cited clinical trials of 14,198 patients on fluoxetine the generic name for Prozac also stated that 2.3 percent of users suffered psychotic depression while on the drug, more than double the next-highest rate of patients using another antidepressant.

In addition, the paper said that 1.6 percent of patients reported incidents of hostility more than double the rate reported by patients on any of four other commonly used antidepressants.

The trials reviewed in the document said tAahat 0.8 percent of users of Prozac reported causing an intentional injury, eight times the rate associated with any of the other antidepressants.

In the paper, titled "Activation and sedation in fluoxetine clinical trials," the authors said that the drug may produce nervousness, anxiety, agitation or insomnia in 19 percent of patients, and sedation in 13 percent of patients.

The paper, apparently produced by the drug company's marketing department, said "several suggestions may be helpful in presenting this information to physicians," including emphasizing that more patients on another class of antidepressants stopped taking their drugs than did those on Prozac.
Murder, theft and deals

The existence of the document obtained by CNN and other documents was reported last week by the British Medical Journal. Its editors said the documents had been reported missing from a 10-year-old murder case, and that they had sent them to the Food and Drug Administration for review.

A spokesman for Lilly said his company was expecting the release of the purported internal documents, but that he could not comment until he had seen them.

The journal said the documents disappeared in 1994 during the case of Joseph Wesbecker, a printing press operator who had killed eight people at his Louisville, Ky., workplace five years before while taking fluoxetine. He then shot and killed himself.

Each of the four pages of the paper obtained by CNN is stamped "Confidential" and "Fentress," the name of one of Wesbecker's victims.

In a civil suit against Eli Lilly, victims' relatives contended the company had long known about the side effects of fluoxetine, including its alleged role in increasing a user's propensity to violence.

Lilly initially won the case, but it was later forced to admit that it had made a secret settlement with the plaintiffs during the trial, which meant that the verdict was invalid, the journal said.

The FDA has recently warned that antidepressants can cause side effects such as agitation, panic attacks, insomnia and aggressiveness.

FDA spokeswoman Susan Cruzan said last week that the agency had no comment on the documents.

In a statement posted on Lilly's Web site, the company said, "To our knowledge, there has never been any allegation of missing documents from the Wesbecker trial or any other trial involving Lilly. Further, it has always been Lilly's objective to publicly disclose data about both the safety and efficacy of fluoxetine.

"Lilly has made several requests to the BMJ to obtain copies of the supposed 'missing' documents; we still await these documents. We are surprised and concerned that a leading medical journal would not find it important to share these documents with us so that we could respond to the public in a meaningful way."

Based on its history of having provided regulatory authorities with study results, the statement said, "Lilly believes that there is no new scientific information to review on this topic."

BMJ TURNS OVER MISSING PROZAC DOCUMENTS TO FDA; LILLY DENIES ANY MISSING DOCUMENTS

Tue, 04 Jan 2005 00:00:00 -0800

The British Medical Journal (BMJ) sent the Food and Drug Administration documents submitted by an anonymous source that seem to show a link between Eli Lilly and Co.s Prozac (fluoxetine) and suicide attempts and violence, according to a BMJ press release. BMJ also said the documents imply that Lilly officials were aware of Prozacs side effects but tried to minimize any negative effect on prescribing the drug. Lilly denied any knowledge of such documents in its own press release.

According to the BMJ, the documents were lost during the trial of Joseph Wesbecker who killed eight people at his work in 1989 and then shot and killed himself. He was taking Prozac at the time. One of the documents, dated November 1988, reported that clinical trials showed that Prozac might cause behavioral problems.

Lilly won a civil suit brought by some relatives of Wesbeckers victims in 1994 but later said it had secretly settled with the plaintiffs during the trial, making the verdict invalid.

Dr. Richard Kapit, the FDA clinical reviewer who approved Prozac, said he was not given the Lilly data. Kapit told BMJ, These data are very important. If this report was done by or for Lilly, it was their responsibility to report it to us and to publish it.

In a press release responding to the BMJ, Lilly said, To our knowledge, there has never been any allegation of missing documents from the Wesbecker trial or any other trial involving Lilly. Further, it has always been Lilly's objective to publicly disclose data about both the safety and efficacy of [Prozac]. Lilly has made several requests to the BMJ to obtain copies of the supposed 'missing documents; we still await these documents. We are surprised and concerned that a leading medical journal would not find it important to share these documents with us so that we could respond to the public in a meaningful way.

Journal: Prozac Side Effects Were Known

Mon, 03 Jan 2005 00:00:00 -0800

A British medical journal said it had given U.S. regulators confidential drug company documents suggesting a link between the popular anti-depressant Prozac and a heightened risk of suicide attempts and violence.

The British Medical Journal reported in its Jan. 1 issue that documents it received from an anonymous source indicated that Prozac's manufacturer, Eli Lilly & Co., was aware in the 1980s that the drug could have potentially troubling side effects.

The journal said the documents, reportedly missing for a decade, had formed part of a 1994 lawsuit against Eli Lilly on behalf of victims of a workplace shooting in Louisville, Ky. Joseph Wesbecker, the gunman who killed eight people and himself in 1989, had been prescribed Prozac a month before the shootings.

Eli Lilly won the case, but later disclosed it had settled with the plaintiffs during the trial.

The journal said one of the records, dated November 1988, reported that fluoxetine, the generic name for Prozac, had caused "behavioral disturbances" in clinical trials.

The journal said it had turned the documents over to the U.S. Food and Drug Administration, which had agreed to review them.

"To our knowledge, there has never been any allegation of missing documents from the Wesbecker trial or any other trial involving Lilly," the company said in a statement. Lilly said it has always been its objective to disclose data about the safety and efficacy of Prozac.

"Lilly has made several requests to the BMJ to obtain copies of the supposed 'missing' documents; we still await these documents," the statement said. "We are surprised and concerned that a leading medical journal would not find it important to share these documents with us so that we could respond to the public in a meaningful way."

The company said it has consistently provided regulatory agencies with results from both clinical trials and safety monitoring after the drug was approved.

In October, FDA ordered that all anti-depressants carry warnings that they "increase the risk of suicidal thinking and behavior" in children.

FDA To Review "Missing" Drug Company Documents

Fri, 31 Dec 2004 00:00:00 -0800

The US Food and Drug Administration has agreed to review confidential drug company documents that went missing during a controversial product liability suit more than 10 years ago. The documents appear to suggest a link between the drug fluoxetine (Prozac), made by Eli Lilly, and suicide attempts and violence.

The missing documents, which were sent to the BMJ by an anonymous source last month, include reviews and memos indicating that Eli Lilly officials were aware in the 1980s that fluoxetine had troubling side effects and sought to minimise their likely negative effect on prescribing.

The documents received by the BMJ reportedly went missing during the 1994 Wesbecker case that grew out of a lawsuit filed on behalf of victims of a work-place shooting in 1989. Joseph Wesbecker, armed with an AK-47, shot eight people dead and wounded another 12. He then shot and killed himself. Mr Wesbecker, who had a long history of depression, had been placed on fluoxetine one month before the shootings.

One of the internal company documents, a report of 8 November 1988, entitled "Activation and Sedation in Fluoxetine Clinical Trials," found that in clinical trials "38% of fluoxetine-treated patients reported new activation but 19% of placebo-treated patients also reported new activation yielding a difference of 19% attributable to fluoxetine."

The FDA recently issued a warning that antidepressants can cause a cluster of "activating" or stimulating symptoms such as agitation, panic attacks, insomnia, and aggressiveness. Dr Joseph Glenmullen, a Harvard psychiatrist and author of The Antidepressant Solution, published by Free Press, said it should come as little surprise that fluoxetine might cause serious behavioural disturbances, as it is similar to cocaine in its effects on serotonin.

Dr Richard Kapit, the FDA clinical reviewer who approved fluoxetine, said he was not given the Lilly data. "These data are very important. If this report was done by Lilly or for Lilly, it was their responsibility to report it to us and to publish it."

Congressman Maurice Hinchey's office is currently reviewing the documents to determine whether Lilly withheld data from the public and the FDA. Mr Hinchey (Democrat, New York) said: "This is an alarming study that should have been shared with the public and the FDA from the get-go, not 16 years later.

"This case demonstrates the need for Congress to mandate the complete disclosure of all clinical studies for FDA-approved drugs so that patients and their doctors, not the drug companies, decide whether the benefits of taking a certain medicine outweigh the risks."

The plaintiffs in the Wesbecker product liability sought to show that Eli Lilly withheld negative study data from the FDA and that fluoxetine tipped Wesbecker over into a homicidal rage. Lilly won a 9 to 3 jury verdict in late 1994 and subsequently claimed that it was "proven in a court of law that Prozac is safe and effective."

The trial judge, Justice John Potter, suspecting that a secret deal had been struck, pursued Lilly and the plaintiffs, eventually forcing Lilly in 1997 to admit that it had made a secret settlement with the plaintiffs during the trial. Infuriated by Lilly's actions, Judge Potter ordered the finding changed from a verdict in Lilly's favour to one of "dismissed as settled with prejudice," saying, "Lilly sought to buy not just the verdict but the court's judgment as well."

David Graham, currently associate director in the FDA's Office of Drug Safety, criticised the analysis of post-marketing surveillance data submitted by Lilly to the FDA. After discovering that Lilly failed to obtain systematic assessments of violence and had excluded 76 of 97 cases of reported suicidality, Dr Graham concluded in a memo dated 11 September 1990 that "because of apparent large-scale underreporting, [Lilly's] analysis cannot be considered as proving that fluoxetine and violent behavior are unrelated."

An FDA advisory panel was convened in 1991 to review the fluoxetine data. It concluded that fluoxetine was safe despite the concerns raised by Dr Graham and others, leading critics to point out that several of the panellists had financial ties to Eli Lilly.

Dr Glenmullen said the missing documents obtained by the BMJ provide "the missing link" between the recent advisory issued by the FDA and what Lilly scientists knew 16 years ago.

Since the 1991 FDA hearings Dr Peter Breggin, who served as the medical expert in the Wesbecker case, has warned that the stimulant effects of fluoxetine can cause suicide and violence. He cautions that the 38% activation rate reported in the missing document is probably low because "it doesn't include other symptoms of activation such as panic attacks, hypomania, and mania."

Dr Kapit, the original reviewer for fluoxetine, told the BMJ, "If we have good evidence that we were misled and data were withheld then I would change my mind [about the safety of fluoxetine]. I do agree now that these stimulatory side effects, especially in regards to suicidal ideation and homicidal ideation, are worse than I thought at the time that I reviewed the drug."

Lilly declined to be interviewed but issued a written statement saying, "Prozac has helped to significantly improve millions of lives. It is one of the most studied drugs in the history of medicine, and has been prescribed for more than 50 million people worldwide. The safety and efficacy of Prozac is well studied, well documented, and well established."

FDA Reportedly Reviewing Eli Lilly Prozac Papers

Fri, 31 Dec 2004 00:00:00 -0800

The U.S. Food and Drug Administration is reviewing internal Eli Lilly documents that suggest the antidepressant Prozac may be linked to violent behavior, the Wall Street Journal reported Friday, quoting a U.K. medical journal.

The documents, which were part of a 1994 civil suit against Prozac maker Eli Lilly (LLY), had disappeared, the British Medical Journal reported. The BMJ recently received the papers through an anonymous sender and turned them over to the FDA, according to the Jan. 1 issue of the publication.

A spokeswoman for the FDA declined to comment, the Wall Street Journal reported. An Eli Lilly communications manager said the company couldn't comment because it hadn't seen copies of the documents cited by the report, the Journal said.

The Wall Street Journal said that the British Medical Journal reported the documents appear to suggest a link between Prozac and suicide attempts and violence.

The documents were being used in the case of Joseph Wesbecker, who in 1989, while being treated with Prozac, went on a shooting spree, killing eight people before killing himself.

The FDA recently warned that Prozac and similar antidepressants could cause "activation" stimulating agitation, panic attacks and aggression.

Journal Hands Over Prozac Papers

Fri, 31 Dec 2004 00:00:00 -0800

Confidential papers on anti-depressant drug Prozac that went missing during a murder case have been handed to the US drug regulator by a UK medical journal.

The documents, belonging to Eli Lilly, the makers of Prozac, included details of clinical trials of the drug, the British Medical Journal said.

The documents reportedly went missing after the relatives of the victims of Joseph Wesbecker started legal action.

Mr Wesbecker, who was on Prozac, shot eight people dead in 1989 in the US.

Another 12 people were injured during the shooting spree at a printing plant in Louisville, Kentucky.

Data

The 47-year-old then shot himself.

In 1994, the relatives brought a civil case against Eli Lilly.

The company subsequently won the case but was later forced to admit that it had made a secret settlement with the plaintiffs during the trial, which meant that the verdict was invalid, the BMJ reported.

Dr Richard Kalpit, the clinical reviewer at the US Food and Drug Administration, the US drugs regulator, who approved the drug, told the BMJ he was not given the data included in the documents.

"These data are very important. If this report was done by Lilly or for Lilly, it was their responsibility to report it to us and to publish it."

Recent research has suggested children who use Prozac are at greater risk of suicide.

And earlier this month the Medicines and Healthcare Products Regulatory Authority said analysis of both published and unpublished data by experts on the Committee on Safety of Medicines showed "a modest increase in the risk of suicide from SSRIs [such as Prozac and Seroxat] compared to placebos [dummy pills]" in adults.

The FDA is now reviewing the papers, which were given to the BMJ by an anonymous source.

Confidential

BMJ deputy editor Dr Tony Delamothe said the journal had handed the confidential drug company documents to the FDA as it believed healthcare decisions need to be made using all the information available.

"The BMJ is committed to ensuring that results good, bad, or indifferent are reported."

A spokesman for Eli Lilly said it would not be appropriate to comment on the content of the papers as officials from the company have not seen them.

But he added: "Lilly is committed to the public disclosure of all clinical trial data to ensure that healthcare professionals and families have the information they need to make informed treatment decisions about Lilly medicines.

"Prozac has been prescribed for more than 50m people worldwide and is one of the most studied drugs in the history of medicine."

Eli Lilly In Storm Over Prozac Evidence

Thu, 30 Dec 2004 00:00:00 -0800

Eli Lilly, the US drug company, suppressed evidence that Prozac, its best-selling antidepressant, could cause behavioural disturbances, according to allegations published on Thursday in the British Medical Journal.

The US Food and Drug Administration says it would review confidential Lilly documents handed over by the BMJ, which received them this month from an anonymous source. The reports and memos appear to suggest Lilly officials knew in the 1980s that Prozac had troubling side-effects and sought to minimise their likely adverse effect on prescribing.

The journal says the documents went missing 10 years ago during a controversial product liability lawsuit filed on behalf of victims of Joseph Wesbecker, who shot eight colleagues dead, wounded 12 more and then killed himself. Mr Wesbecker had a history of depression and was prescribed Prozac a month before the shootings.

One document, a clinical trial review dated November 1988, stated that 38 per cent of patients treated with Prozac but only 19 per cent of those given a placebo reported new activation.

The FDA recently warned that Prozac and similar antidepressants could cause activation stimulating agitation, panic attacks and aggression.

In a statement defending its product, Lilly said: Prozac has helped to significantly improve millions of lives. It is one of the most studied drugs in the history of medicine, and has beenprescribed for more than 50m people worldwide. The safety and efficiency of Prozac is well studied, well documented and well established.

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.

A Belated Admission On Antidepressants By the FDA

Thu, 16 Sep 2004 00:00:00 -0700

The Food and Drug Administration finally acknowledged publicly this week what some in the drug industry had known for a while but had declined to reveal: Antidepressants drugs such as Effexor, Paxil, Zoloft and Prozac appear to cause a small number of children and teenagers who use them to become suicidal or have suicidal thoughts.

And a scientific advisory committee voted 15-8 on Tuesday to recommend to the FDA that it put a "black box" warning on the labels for the antidepressants about the suicide risk for the youths who take them.

Legitimate questions have arisen about whether the drug industry wanted to keep quiet drug-test results that might hurt profits and about a federal agency more attuned to not irritating the drug industry than protecting the public welfare.

In February the FDA put a lid on findings by its own analyst, Andrew Mosholder, who warned of a link between use of the drugs and youth suicide.

Now he's been vindicated, and there's a bipartisan push in Congress to find out why this information was kept quiet for so long.

This week, Robert Temple, director of the FDA office of medical policy, said a review of 15 clinical trials some kept secret for years by drug companies show "there is an increase in suicidal thinking and action that is consistent across all the drugs."

There's also reason to believe that the danger of suicide from the drugs, however few children or teenagers it might affect, is not offset by doing good for many others.

"What is troubling is that millions of antidepressant prescriptions are written for depressed kids, when the facts show that six of the seven anti-depressants tested in pediatric trials did not show efficacy in kids," Rep. Greg Walden, R-Ore., said last week.

A House investigations subcommittee is studying use of the drugs and the suppression of clinical trial findings about their effects.

The industry has said the usefulness of the drugs remains undetermined even though almost 11 million prescriptions are given out a year.

Some parents strongly believe antidepressants have helped their children.

But other parents whose children have committed suicide while using antidepressants have criticized the FDA for taking too long to acknowledge the risks.

And British health authorities restricted most antidepressants for children and teenagers last December.

Congress must ensure that the information from drug trials is made public and that the FDA is not a party to suppressing information discomforting to the drug industry.

Parents have a right to know all of the risks their child takes with a drug, even if the risks are slight.

And if the FDA doesn't know what the risks of a drug are, why is it approving their use at all?

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.

Antidepressants And Suicide Linked

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

Two to 3 percent of children treated with antidepressants had suicidal thoughts or behavior as a result of the drugs, officials said yesterday, based on the Food and Drug Administration's most comprehensive analysis of past clinical trials of the widely used drugs.
In a sharp departure from a decade-old position, agency officials said the increase in suicidal tendencies was not a result of the children's underlying depression but was caused by the medications themselves.

"Out of 100 patients treated, we may expect to see two to three patients (who) will experience increases in suicidality due to short-term treatment," said Tarek Hammad, the FDA analyst who conducted the latest review. The increase, he said, "is beyond the suicidality as a result of the disease being treated."

Senior FDA officials acknowledged that the results of the new analysis were substantially the same as the conclusions reached nearly seven months ago by an agency scientist who also found an increase in suicidal tendencies in children taking the medications.

At the time, the FDA declined to make the conclusions of staff scientist Andrew Mosholder public, citing a lack of confidence in his results.

Hammad spoke on the first day of a two-day hearing by an FDA advisory panel on the controversy over the reported risks of prescribing antidepressants to young people.

Robert Temple, the FDA's associate director for medical policy, defended the decision not to present Mosholder's conclusions in March. "Obviously people can disagree," he said.

At a news briefing that included Mosholder and Hammad, Temple said the FDA realized that taking these drugs might increase suicidal tendencies.

"But depression alone is a cause of potential suicide," he said, "so scaring people needlessly and overdoing it is worrisome also."

Parents and other critics of the FDA had accused senior officials of having turned a blind eye to the worrisome data. But Temple, Hammad and Mosholder agreed that the studies lent themselves to differing interpretations, in part because they were not originally designed to answer questions about suicidal tendencies. While individual clinical trials sometimes contradicted each other, the FDA officials said a broad pattern of evidence had emerged that, on average, children taking the medications had about twice the risk of developing suicidal behavior or thoughts compared with children receiving a placebo.

"It's very consistent," Temple said, adding that regulators today would examine whether the drugs' labeling should be modified and whether some drugs for children should be recommended to physicians ahead of others.

The controversy over the drugs is the subject of several congressional inquiries. Physicians and families have complained that pharmaceutical companies had kept secret the results of more than half the trials that found the drugs were no more effective than placebos.

Prozac is so far the only medicine approved by the FDA specifically to treat children's depression, but physicians routinely prescribe other drugs of the same type, called selective serotonin reuptake inhibitors, to millions of American children.

Experts had previously said that studies of Prozac turned up no increase in suicidal tendencies, but its unique status came into question yesterday.

Hammad testified that a recent government-sponsored study, which researchers had described as convincing evidence of Prozac's effectiveness, found it carried the same risk of triggering suicidal behavior as other drugs.

In March, the FDA officials issued an advisory to physicians reminding them to be vigilant to the possibility of suicide in children and adults taking the drugs.

The data presented yesterday suggested increased suicidal tendencies seen in the trials may be unique to children.

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.

Prozac Raises Child Suicide Risk

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

Children who take the anti-depressant Prozac are at greater risk of attempting suicide, say US experts.

The drug is currently the only anti-depressant which doctors can prescribe to under-18s in the UK.

Other similar drugs are considered too dangerous because previous studies have linked them to an increase in suicidal tendencies.

However, an analysis by the US Food and Drug Administration has found that Prozac too may pose a risk.

The analysis was overseen by Dr Robert Temple, director of the FDA office of drug evaluation, who gave evidence on Tuesday at a hearing to determine whether tougher warning labels were needed for anti-depressants.

He said: "I think we now all believe there is an increase in suicidal thinking and action that is consistent across all the drugs."

On average, the analysis, carried out by experts at Columbia University, New York, found anti-depressants taken by children will cause an extra 2% to 3% to have increased suicidal thoughts.

Relative risks of suicidal behavior were highest among young people taking Luvox, Effexor and Paxil and lower but still heightened among those taking Celexa, Zoloft and Prozac.

Dinah Morley, of the charity Young Minds, told BBC News Online: "Children who are put on these heavy duty drugs are very ill, and sadly more likely to commit suicide anyway.

"We would urge the greatest care possible to be taken in using these medications, but there are times when a young person is so deeply depressed that anything that may help must be considered because the alternative is death."

A Department of Health spokesperson said: "The Medicines and Healthcare products Regulatory Agency is reviewing these new data and will seek the advice of the Committee on the Safety of Medicines on what if any implications there are for the current advice that the balance of benefits and risks of Prozac (fluoxetine) is favourable in the treatment of depression in children and adolescents.

"As with all medicines, the MHRA/CSM keep the safety of fluoxetine under critical review."

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.

Prozac Suicide SSRI Side Effects Lawsuit

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

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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. Reports of suicidal behavior in children and adolescents taking Eli Lilly & Co.'s Prozac (Generic: Fluoxetine) are becoming widespread. Prozac was introduced in the U.S. in 1988 and is the only antidepressant certified as safe for children. Robert Temple, director of the Office of Drug Evaluation at the FDA, said that a large new study added to previous research on Prozac and showed that kids taking the drug have about a 50 percent higher risk of suicidal thoughts and suicide attempts. Temple spoke at the first day of hearings on potential label changes for antidepressants taken by more than a million children and teenagers.

Following a February 2004 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 thought the move came 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.

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. On average, antidepressants taken by kids will cause an extra 2 percent to 3 percent to have increased suicidal thoughts, the independent experts, working with Columbia University, found.

Relative risks of suicidal behavior were highest among youths taking Luvox, Effexor and Paxil and lower among youths taking Celexa, Zoloft and Prozac. Two FDA advisory panels are considering whether agency action including stronger warning labels is needed on nine antidepressants linked to heightened suicidal tendencies among children.

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