Yourlawyer.com (Effexor News)

Baystate Medical Center Subpoenaed Over Fake Drug Studies

Wed, 08 Apr 2009 00:00:00 -0700

The Baystate Medical Center has received a subpoena as part of a federal investigation into a doctor there who falsified 21 drug studies. According to The Wall Street Journal, the U.S. Attorneys office in Boston is seeking financial records related to the work of Dr. Scott S. Reuben.

As we reported last month, medical journals have been asked to retract studies involving Vioxx, Celebrex, Lyrica and other drugs. All of the studies were published between 1996 and 2008. According to The Wall Street Journal, the journal Anesthesia & Analgesia has retracted 10 studies. It also posted a list of 11 others that were published in other journals on its Web site. The journal Anesthesiology said it has retracted three of Reuben’s articles.

These studies had a great deal of influence on the practice of medicine. Because of Reuben’s “research”, it had become routine for doctors to combine the use of painkillers like Celebrex and Lyrica for patients undergoing common procedures such as knee and hip replacements. Reuben even had the ear of the Food & Drug Administration, and had written the agency asking it not to restrict the use of many of the painkillers he studied. He often cited his fake data to make his case, the Journal said.

Many of the studies Reuben worked on involved drugs that have very serious side effects. Like many antidepressants, the labeling of Effexor warns that it has been linked to suicides in young people and children. Both Celebrex and Vioxx have been linked to heart attacks and strokes, and Vioxx was actually recalled in 2006 because of these problems.

Not surprisingly, Reuben has strong ties with the pharmaceutical industry. According to the Journal, he had been a paid speaker on behalf of Pfizer - the maker of Lyrica and Celebrex - and it paid for some of his research. Wyeth provided $10,000 in grant money to. Reuben from 2001 to 2003, the Journal said. Merck also funded some of Reuben's work.

According to The Wall Street Journal, Baystate Medical is cooperating fully with the federal government's probe of Reuben. A spokesperson for the Springfield, Mass., medical center told the Journal that Baystate isn't a target of the investigation.

Baystate Medical Center has placed Reuben on indefinite leave. He has also vacated an appointment as a professor at Tufts University’s medical school, the Journal said.

Researcher Faked Data for 21 Studies Involving Vioxx, Celebrex and Other Drugs

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

Medical journals have been asked to retract 21 studies that touted the benefits of Vioxx, Celebrex and other drugs. According to The Wall Street Journal, Baystate Medical Center, Springfield, Mass. is asking the journals to make the retractions because its former chief of acute pain, Dr. Scott S. Reuben, had faked data used in the studies.

In addition to Vioxx and Celebrex, some of the 21 studies involved the fibromyalgia drug Lyrica and the antidepressant Effexor XR. Reuben's study claimed to show that these drug worked well as painkillers, the Journal said. All of the studies were published between 1996 and 2008.

According to The Wall Street Journal, these studies had a great deal of influence on the practice of medicine. Because of Reuben's "research", it had become routine for doctors to combine the use of painkillers like Celebrex and Lyrica for patients undergoing common procedures such as knee and hip replacements, the Journal said.

Reuben even had the ear of the Food & Drug Administration (FDA), and had written the agency asking it not to restrict the use of many of the painkillers he studied. He often cited his fake data to make his case, the Journal said.

According to The Wall Street Journal, Reuben's fraud has caused the journal Anesthesia & Analgesia to retract 10 studies. It also posted a list of 11 others that were published in other journals on its Web site. The journal Anesthesiology said it has retracted three of Reuben's articles.

Not surprisingly, Reuben has strong ties with the pharmaceutical industry. According to the Journal, he had been a paid speaker on behalf of Pfizer - the maker of Lyrica and Celebrex - and it paid for some of his research.

Baystate Medical Center has placed Reuben on indefinite leave. He has also vacated an appointment as a professor at Tufts University's medical school, the Journal said.

Perhaps the most disturbing aspect of this scandal is that many of the drugs Reuben researched have been linked to serious side effects. Like many antidepressants, the labeling of Effexor warns that it has been linked to suicides in young people and children.

Both Celebrex and Vioxx have been linked to heart attacks and strokes, and Vioxx was actually recalled in 2006 because of these problems.

This is actually not the first time the integrity of studies involving Vioxx have come into question. Last April, we reported that an analysis of court documents uncovered in the course of Vioxx injury lawsuits found that Merck & Co. employees worked alone or with publishing companies to write Vioxx study manuscripts and later recruited academic medical experts to put their names as first authors on the studies. According to the analysis, which was published in the Journal of the American Medical Association, Merck’s involvement in producing the data wasn’t disclosed in many cases.

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.

Emory Researcher Sanctioned for Failing to Disclose Drug Company Payments

Tue, 23 Dec 2008 00:00:00 -0800

A prominent Emory University professor has lost a chairmanship as a result of a controversy stemming from payments he received from drug companies. The Wall Street Journal reported today that Charles Nemeroff is stepping down from his position as head of the school's Department of Psychiatry and Behavioral Sciences, position he has held since 1991, following an internal investigation. The university will also be restricting Nemeroff's research and extracurricular activities.

Nemeroff has been cited several times in an investigation being conducted by Sen. Charles Grassley (R-Iowa), who has been probing the financial ties between medical researchers and the pharmaceutical industry. As Grassley's investigation focused more and more on Nemeroff's possible conflicts-of-interest, Emory promised an investigation.

According to The Wall street Journal, that investigation found that Nemeroff failed to report to Emory more than $800,000 he received from Glaxo for more than 250 speaking engagements from Jan. 2000 to Jan. 2006. According to the Atlanta Constitution-Journal, Emory's investigation also found that Nemeroff received income from other drug makers, but Glaxo was by far his biggest patron.

In October, we reported that documents released by Emory to Grassley’s investigators indicated that Nemeroff was paid more than $2 million by pharmaceutical companies, but failed to report more than $1 million of that income to the school while working on government-funded drug researcher. Those documents include a letter from Nemeroff dated July 15, 2004 in which he promises Emory administrators that he would earn less than $10,000 a year from GlaxoSmithKline to comply with federal rules. But in that same year, Nemeroff actually earned $170,000 from Glaxo for giving talks about Paxil and other drugs the company made.

According to a report in The Wall Street Journal last week, Emory has tried to explain the Glaxo payments by claiming they were for talks that weren’t promotional in nature but instead were “CME-like” (a term for continuing medical education). Emory claims that the distinction led Nemeroff to believe he didn’t need to disclose those payments, the Journal said.

But in a letter dated Dec. 17, Grassley voiced skepticism. “Neither anyone on my staff, nor any medical expert that they have contacted, have ever heard of the term ‘CME-like,’” he wrote. “It appears to be a new term created at Emory University.”

Grassley also criticized Nemeroff for a letter he wrote in 2000 when he was also serving as editor in chief of the journal Depression and Anxiety. According to the Journal, which termed the missive a “Dear Me” letter, Nemeroff wrote it on the journal’s letterhead, and indicated he being paid $3,000 by the publication to write an article about Wyeth Pharmaceutical’s antidepressant, Effexor. But Nemeroff also billed Emory that exact amount for the article. It’s not clear if Nemeroff received two payments of $3,000, one from Emory and one from the journal.

According to The Wall Street Journal, 14 other Emory faculty members received similar payments to write Effexor articles for the same issue of Depression and Anxiety. Grassley says their payments, and the $3,000 Nemeroff received from Emory actually came from a grant furnished by Wyeth. According to the senator, the issue of Depression and Anxiety where the articles appeared fails to mention that any of the authors, including Nemeroff, received payments from a Wyeth grant.

In addition to reaching an agreement with Nemeroff to leave the department chairman post, The Wall Street Journal reported that Emory will not submit any National Institutes of Health grant or contract requests in which Nemeroff is listed as an investigator for two years. Nemeroff will also need pre-approval from the dean of the medical school for any outside income, the Journal-Constitution 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.

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.

Published Antidepressant Studies Exaggerate Their Effectiveness

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

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

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

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

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

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

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

Effexor XR Claims in Ad Draw FDA Rebuke of Wyeth

Tue, 18 Dec 2007 00:00:00 -0800

Ads for Effexor XR in a medical journal are misleading, the Food & Drug Administration (FDA) says, prompting the agency to issue a warning letter to Wyeth, the maker of the widely-used antidepressant. The FDA said the wording of the ad overplays the benefits of Effexor XR and minimizes dangerous side effects.

Effexor XR is an extended version of the original Effexor. Effexor is the top selling anti-depressant in the world, according to Wyeth, and Effexor drugs reaped sales of $958 million in the third quarter of 2007 alone.

Effexor and Effexor XR work by increasing the brain’s uptake of the neurotransmitters serotonin and norepinephrine, both of which effect mood. But both drugs are known to have dangerous side effects, including an increased risk of suicidal thoughts and behavior when used in children and adolescents, as well as hypertension and serious withdrawal symptoms. Despite such serious side effects, Effexor and Effexor XR are marketed by Wyeth as better alternatives to antidepressants like Paxil, Prozac and Zoloft.

Now, the FDA is charging that an ad which appeared in a medical journal makes “unsubstantiated superiority” claims about Effexor XR. The FDA criticized several claims in the ad, including citation of a study claiming that said Effexor XR prevented a depressive episode in 92 percent of cases, versus 55 percent for a placebo. The agency said that claim is "based on a study that is inadequate."

The FDA also faulted Wyeth's claim that 20 million people have been treated with the Effexor XR, a statistic the FDA said is based on suspect data. Because people may associate the number of people treated with quality, this claim "may mislead consumers and healthcare providers," FDA wrote.

This is not the first time Wyeth has been accused of making misleading Effexor claims. Last month, Dr. Daniel Carlat recounted his experiences as a Wyeth-paid Effexor lecturer in the New York Times. According to Dr. Carlat, the Effexor information Wyeth instructed him to convey during visits to physician offices was often incomplete, downplayed risks, and was skewered to favor Effexor over other drugs. When Dr. Carlat, uncomfortable with the Wyeth-provided script, altered it to include more complete data on hypertension, he was visited by a district manager, who expressed concern that the doctor was not exhibiting enough “enthusiasm” in his talks. Dr Carlat quit lecturing for Wyeth shortly after that episode.

The FDA has ordered Wyeth to cease running ads for Effexor XR that make misleading claims in medical journals. The company must also provide the FDA with a list of other Effexor XR marketing materials that make similar claims, as well as a detailed plan for discontinuing the use of such materials. Wyeth has until December 21 to respond to the FDA Effexor XR warning letter.

The Effexor XR ads in question are no longer running, but a spokesperson for Wyeth told Reuters that the company believes they were “responsible.”

Effexor XR Side Effects Downplayed During Talks, Former Wyeth-Paid Lecturer Charges

Mon, 26 Nov 2007 00:00:00 -0800

Effexor XR, a popular antidepressant, is probably no more affective than other such medications, and unlike other antidepressants, Effexor is associated with hypertension and serious withdrawal symptoms. But doctors who got information from physician -lecturers paid by Wyeth Pharmaceuticals to promote Effexor XR might not know that. According to a former Effexor XR physician-lecturer who recently came forward to describe his experience in this role, the Effexor information provided during such talks was often incomplete, downplayed risks, and was skewered to favor Effexor over other drugs. Dr. Daniel Carlat recently recounted a story in the New York Times that raises serious questions about the ways pharmaceutical companies often market their drugs.

According to Dr. Carlat, a psychiatrist with a specialty in psychopharmacology, Wyeth first approached him in 2001, asking if he would be willing to give talks to primary care physicians about Effexor XR, a drug used in treating depression. Effexor XR was being marketed by Wyeth as a better alternative to antidepressants like Paxil, Prozac and Zoloft. Effexor XR works by increasing the brain's uptake of the neurotransmitters serotonin and norepinephrine, both of which effect mood. Traditional antidepressants like Paxil only increase serotonin uptake. Dr. Carlat was familiar with some positive studies involving Effexor XR, and had prescribed it to his patients. Wyeth's offer of a $500-$750 stipend for each Effexor XR talk he gave helped convince Dr. Carlat to take the company up on its offer.

Dr. Carlat and was first sent by Wyeth to a conference in New York City, where the doctor would receive "education" on Effexor XR. The drug company put Dr. Carlat and his wife up in a posh Manhattan hotel, provided the couple with tickets to a Broadway Show, and paid him $750 just for attending the conference. At the Effexor XR "education classes", prominent scientists - all paid by Wyeth --touted the drug as a big improvement over other medications. One researcher emphasized Effexor XR's remission rate - complete cure -which the company said was 10% better than other antidepressants. This bothered Dr. Carlat somewhat, as antidepressant effectiveness is usually measured by response rate, which is defined as a 50% improvement in symptoms. In his New York Times piece, Dr. Carlat admits that he wondered if Wyeth had chosen to emphasize remission in order to make Effexor XR look better than it truly was.

Another researcher spent much of his lecture downplaying Effexor XR's association with high blood pressure - a side effect not shared by other antidepressants. According to the speaker, Effexor XR only had a slight chance of elevating blood pressure. The conference also downplayed problems experienced by people who stopped taking the drug - including dizziness, mood changes, and even nervous breakdowns - that where more serious than those associated with other antidepressants.

At the end of the conference Dr. Carlat went home to begin with his new role as "Dr. Drug Rep." But as month's passed, he became increasing uneasy serving as an Effexor XR cheerleader. For one thing, Dr. Carlat kept up with Effexor XR developments, and as more research became available, it was clear that Effexor was not significantly better than other antidepressants. He also learned that some of the Wyeth studies cited at the Effexor XR conference had been conducted in a way that was beneficial to Effexor. Dr. Carlat also became aware of studies that showed Effexor XR's risk of hypertension was greater than previously thought.

Still, Dr. Carlat continued giving Effexor talks, downplaying risks and highlighting benefits. Finally, during one of his Effexor lectures, Dr. Carlat was challenged by a doctor over Wyeth's hypertension data. This bothered him enough that he altered his lectures from the approved Wyeth format, and decided to begin ending his Effexor talks with the caveat that the Effexor studies he cited were mainly short-term, and that there was a possibility that other antidepressants were just as effective as Effexor. The first lecture he gave with this warning resulted in Dr. Carlat receiving a visit from a Wyeth district manager, concerned that the doctor was not exhibiting enough "enthusiasm" in his talks. According to Dr. Carlat, he decided then and there to end his association with Wyeth.

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.

Wyeth revises Effexor label over overdose risk

Wed, 25 Oct 2006 00:00:00 -0700

Wyeth (WYE) said Wednesday it revised the label of its blockbuster Effexor drug to include the fact that overdose has been reported, occurring mostly in combination with alcohol and other drugs.

Effexor is indicated for treatment of major depressive disorder. The revision was also made to the extended-release version of Effexor, known as Effexor XR.

In a letter to health-care providers posted on the Food and Drug Administration Web site, the company said death has been reported from overdose of the drug.

The most commonly reported events included tachycardia, changes in levels of consciousness, ranging from somnolence to coma, seizures, and vomiting, it added.

Wyeth also urged health-care professionals to prescribe the smallest quantity of the drug "consistent with good patient management, in order to reduce the risk of overdose."

A company spokeswoman wasn't immediately available to comment.

Effexor Linked to Increased Risk for Death From Overdose

Wed, 25 Oct 2006 00:00:00 -0700

The US Food and Drug Administration (FDA) and Wyeth Pharmaceuticals Inc have notified healthcare professionals via letter regarding the potential increased risk for fatal outcome with an overdose of venlafaxine HCl (Effexor tablets and Effexor XR capsules) compared with that of other selective serotonin reuptake inhibitors (SSRI).

Data from published retrospective studies suggest that venlafaxine overdose may be linked to a risk for mortality that is higher than that for SSRIs but lower than that for tricyclic antidepressants, according to an alert sent today from MedWatch, the FDA's safety information and adverse event reporting program.

Also, epidemiologic data has shown that venlafaxine-treated patients may have a greater preexisting burden of suicide risk factors than those receiving other SSRIs.

In postmarketing reports, overdose with venlafaxine occurred predominantly in combination with alcohol and/or other drugs and most commonly presented as tachycardia, changes in level of consciousness that range from somnolence to coma, mydriasis, seizures, and vomiting.

Other adverse events have included electrocardiogram changes (eg, QT interval prolongation, bundle-branch block, and QRS prolongation), ventricular tachycardia, bradycardia, hypotension, rhabdomyolysis, vertigo, liver necrosis, serotonin syndrome, and death.

To reduce the risk for overdose, the FDA advises that venlafaxine prescriptions be written for the smallest quantity of capsules consistent with good patient management.

Additional information regarding this issue may be obtained by contacting the company's medical communications department at 1-800-934-5556. A related educational and support program ("Dialogues: Time-to-Talk") is available at http://www.mddpatientsupport.com.

Venlafaxine tablets are indicated for the treatment of major depressive disorder only; the capsules and extended-release capsules are also indicated for the treatment of generalized anxiety disorder, social anxiety disorder, and panic disorder.

Adverse events potentially related to venlafaxine therapy should be reported to Wyeth Global Safety Surveillance and Epidemiology and Labeling (GSSEL) by fax to 610-989-5544, or by mail to GSSEL, Wyeth Research, GSSEL-Triage-Dock E, 500 Arcola Road, Collegeville, PA 19426.

Alternatively, reports may be submitted to the FDA's MedWatch reporting program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.

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

Group warns of drug Yates took before deaths

Tue, 11 Jul 2006 00:00:00 -0700

An antidepressant that Andrea Yates had been taking before she drowned her five children in 2001 has recently been found to possibly increase the risk of homicidal thoughts, according to a medical watchdog group that says Effexor's manufacturer has not warned the public.

"Homicidal ideation" was added last year as one of the drug's rare adverse events on Effexor XR's label and on the Web site of its manufacturer, Wyeth.

The U.S. Food and Drug Administration defines rare as occurring in less than one in 1,000 people. In the U.S. alone, about 19.2 million prescriptions for Effexor were filled last year, but that does not reflect the number of people who take the drug because some of those are refills.

Dr. Moira Dolan, executive director of the Medical Accountability Network, said she discovered the labeling change about two weeks ago when she stumbled across the FDA's MedWatch newsletter from November. The Madison, N.J.-based drug company did not send letters to doctors or issue warning labels.

"People need to be warned that this is a possible side effect," Dolan, an Austin doctor who has reviewed Yates' medical records but is not involved in the case, said on Sunday.

Wyeth calls drug safe

Effexor is Wyeth's top-selling drug, with $3.46 billion in 2005 sales worldwide, more than twice the total for its No. 2 product and 18 percent of its total revenues for last year. "We believe there is no causal link between Effexor and homicidality," said Wyeth spokeswoman Gwen Fisher. "In our minds, we've taken every precaution."

She said that as Effexor was being studied for use in treating panic disorder, Wyeth found that only one person reported having homicidal thoughts in its clinical trial. Fisher said she did not know the trial date.

In approving Wyeth's application to use Effexor for that disorder, the FDA wanted homicidal ideation listed as a rare adverse event, defined as something not proven to be linked to the drug, Fisher said. That is different from an adverse reaction, she said.

Wyeth never notified doctors or issued warning labels because it found no causal link between its drug and homicidal thoughts, Fisher said. The current Web site label mentioning homicidal thoughts is appropriate, she said.

Linked to suicidal thinking

In 2004, the FDA ordered that all antidepressants carry "black box" warnings that they increase the risk of suicidal thinking and behavior in children. That action was driven by data that showed that, on average, 2 to 3 percent of children taking antidepressants have increased suicidal thoughts and actions. The link is stronger with Effexor than with other antidepressants in the same class of drugs.

But Fisher said the drug is safe and effective. Yates, who remains jailed, continues taking Effexor as well as an anti-psychotic drug to help stabilize her mental illness, said a psychiatrist testifying in Yates' retrial that started two weeks ago.

Yates, 42, has pleaded not guilty by reason of insanity in her second murder trial. Her 2002 capital murder conviction was overturned on appeal because some erroneous testimony may have influenced jurors.

Daily dose was high

Yates had been prescribed Effexor in varying doses since shortly after her first suicide attempt in 1999, said Dolan, who reviewed her medical records after Yates' first trial at the request of Yates' then-husband, Russell Yates. A month before the murders, her daily dose had increased to 450 milligrams, twice the recommended maximum dose, Dolan said.

Her lead attorney, has criticized the amount of medications Yates was prescribed before the children's bathtub drowning deaths. He said Wyeth should have publicized information about the possible connection between Effexor and thoughts of homicide, but he said that will not affect Yates' case.

"Obviously this is a severely mentally ill individual who was on a plethora of psychiatric meds," Parnham said.

"There's no question mental illness killed those children."

Drug's sales increased

Yates attorney claims client suffered from postpartum psychosis and drowned the children in the family bathtub while in a delusional state, which likely was exacerbated after she was suddenly taken off Haldol, a strong anti-psychotic drug.

Yates, being tried in only three of the deaths, will be sentenced to life in prison if convicted.

Effexor sales rose only 3.3 percent in 2005, compared with 2004, but jumped 8.8 percent in the first quarter of this year, to $945 million.

FDA sends Wyeth a warning letter

Tue, 30 May 2006 00:00:00 -0700

The Food and Drug Administration sent Wyeth a warning letter about violations of good manufacturing practices at a plant in Puerto Rico.

The letter, which regulators posted on the agency's Web site Tuesday, said there were problems in the manufacture of several drugs, including birth control pill Triphasil, hormone replacement Prempro, antidepressant Effexor and over-the-counter pain reliever Advil.

Among the violations noted in the May 3 letter from the FDA is the failure to clean and maintain packaging equipment to prevent contamination, plus not adequately inspecting packaging and labeling machines before use to insure all previous products had been removed.

FDA Warns of Suicide Risk for Paxil

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

SSRI Antidepressants Linked To Serious Lung Disorder in Newborns

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

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

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

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

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

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

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

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

America's Top-Selling Prescription Drugs – a Who's Who of Blockbusters

Sat, 04 Mar 2006 00:00:00 -0800

According to a recent article in Forbes.com (2/27/06) that was based on figures obtained from IMS Health, a healthcare information company, the top 20 prescription drugs in the U.S. in 2005, with combined sales of $64.6 billion, were as follow:

1.    LIPITOR – Pfizer – Treats high cholesterol: $8.4 billion

2.    ZOCOR – Merck –Treats high cholesterol: $4.4 billion

3.    NEXIUM – AstraZeneca – Treats heartburn: $4.4 billion

4.    PREVACID – Abbott & Takeda – Treats heartburn: $3.8 billion

5.    ADVAIR DISKUS – GlaxoSmithKline – Treats asthma: $3.6 billion

6.    PLAVIX – Bristol-Meyers Squibb & Sanofi-Aventis – Treats heart disease $3.5 billion

7.    ZOLOFT – Pfizer – Treats depression: $3.1 billion

8.    EPOGEN – Amgen – Treats anemia: $3.0 billion

9.    PROCRIT – Johnson & Johnson – Treats anemia: $3.0 billion

10.    ARANESP – Amgen – Treats anemia: $2.8 billion

11.    ENBREL – Amgen & Wyeth – Treats rheumatoid arthritis: $2.7 billion

12.    NORVASC – Pfizer – Treats high blood pressure: $2.6 billion

13.    SEROQUEL – AstraZeneca – Treats schizophrenia: $2.6 billion

14.    EFFEXOR XR – Wyeth – Treats depression: $2.6 billion

15.    ZYPREXA – Eli Lilly – Treats: schizophrenia: $2.5 billion

16.    SINGULAIR – Merck – Treats asthma and allergies: $2.5 billion

17.    PROTONIX – Wyeth – Treats heartburn: $2.4 billion

18.    RISPERDAL – Johnson & Johnson – Treats schizophrenia: $2.3 billion

19.    NEULASTA – Amgen – Treats chemotherapy side effects: $2.2 billion

20.    REMICADE – Johnson & Johnson – Treats rheumatoid arthritis: $2.2 billion

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.

Murdered teen's parents sue company that sold poison

Thu, 19 Jan 2006 00:00:00 -0800

The parents of a former Centennial High School student whose classmate murdered him in 2003 with potassium cyanide have filed a lawsuit seeking $2 million in damages from the Kentucky company that sold the killer the poison.

Walter Vassiliev and Karen Dale Barrett, the parents of Benjamin Vassiliev, filed suit Dec. 29 in Howard County Circuit Court against Antec Inc., of Louisville, Ky., the company that sold Ryan Furlough the potassium cyanide he used to murder the younger Vassiliev.

The suit also names Furlough's parents, Susan and Thomas Furlough, of Ellicott City, and Furlough's Ellicott City psychiatrist, Richard Bacharach, as defendants, and seeks an additional $2 million in damages from each.

As a result of Ben Vassiliev's murder, his parents have suffered "severe mental anguish and emotional pain," and been deprived of a relationship with their son, according to the suit.

"The main culprit here is Antec," said Paul Bekman, the Baltimore attorney who is representing Vassiliev's parents. "They are the ones who are shipping poison to minors in interstate commerce, without any verification, restriction or protocols. Your son or daughter, who is 14 years old, could call them up, use your credit card, and have them ship poison that can kill 20 people. I don't think that should be the case."

Walter Vassiliev referred questions on the suit to Bekman. Karen Dale Barrett could not be reached for comment.

Furlough sentenced to life

A Howard County jury convicted Furlough of first-degree murder in 2004 for fatally poisoning Vassiliev in 2003.

Judge Raymond Kane Jr. sentenced Furlough to life with the possibility of parole, because, he said, Furlough lacked a criminal record and deserved a chance to show that he might respond to rehabilitation.

Furlough, now 20, and Ben Vassiliev were best friends and classmates at Centennial High School.

At Furlough's May 2004 trial, prosecutors portrayed him as a cold-blooded killer who schemed to poison Vassiliev because he was jealous of Vassiliev's girlfriend.

Defense attorneys argued that crippling depression and high doses of the anti-depressant Effexor left Furlough incapable of reason Jan. 3, 2003, the day he put cyanide in a Vanilla Coke he offered to Vassiliev, who died from the poison five days later.

Negligence claimed in suit

The lawsuit seeks $2 million in damages from Antec Inc., alleging that the company was "negligent and careless" when it sold the potassium cyanide to Furlough.

The suit claims that Anetc failed to maintain detailed records of the sale, including the name of the buyer, the amount of poison sold, or the purpose for the purchase.

Antec "failed to exercise reasonable care in determining who the ultimate purchaser of said poison was to be and the purpose for which it was to be used," the suit states.

William Oesterriter, CEO of Antec Inc., said Jan. 13 that since his company had not yet received a copy of the lawsuit he could not respond to it.

The suit also claims that Bacharach, the psychiatrist who was treating Furlough for depression, is liable for Vassiliev's death because he failed to "disclose information regarding Ryan Furlough's dangerous propensity for violence against Benjamin Vassiliev ... ."

Bacharach did not return a phone call seeking comment.

Suit hurts Furlough family

Vassiliev's parents are suing the Furloughs because they failed to "control their minor child, Ryan Furlough, in his use of the Internet and of their credit card to purchase potassium cyanide knowing that he had previously misused their credit card," according to the suit.

Susan Furlough said her family was hurt by the lawsuit.

"I think it's very uncalled-for," she said. "I find it very upsetting. We've done nothing more than what most parents would do with their children. We've had a very hard three years. It never seems to stop and we've had more than our fair share of grief."

Furlough said she continues to blame the effects of Effexor for her son's behavior and hopes others will learn to avoid putting their children on the drug.

"Maybe people will start paying more attention to these drugs," she said. "Maybe some other families could be put through less grief."

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.

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.

Regulators Recommend Restricted Use of Drug

Mon, 06 Dec 2004 00:00:00 -0800

British regulators recommended on Monday that physicians restrict the use of the anti-depressant Efexor from drugmaker Wyeth because its use could have side effects for heart health and pose other potential risks that require more careful monitoring than other drugs in the class. Wyeth said it would challenge the decision, but its shares slipped 3 percent.

The United Kingdom's Medicines and Healthcare Products Regulatory Agency said the drug, which is marketed as Effexor in the United States, may cause irregular heart rhythms, withdrawal symptoms and have a higher rate of death from overdose than similar drugs.

The agency is recommending that only specialists should prescribe Efexor and that patients should be continually supervised. The drug should also not be prescribed to patients with heart problems, the agency said.

In a statement, Wyeth said it will challenge the agency's action and urged it to accept the company's previous recommendations for labeling, educational initiatives and new packaging to reduce the risk of suicide and overdose.

The anti-depressant is the Madison, N.J.-based pharmaceutical company's best-selling drug.

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.

Drug Firms, Doctors Sued Over Suicide

Wed, 06 Oct 2004 00:00:00 -0700

Parents of an 11-year-old boy who committed suicide after taking antidepressant medications has sued the two companies that make the drugs and three health professionals who oversaw the boy's care.

In a lawsuit filed Tuesday in Douglas County District Court, David and Debra Jackson contend that the Oct. 10, 2002, hanging death of their son, Jacob, was the result of side effects from the antidepressant drugs Zoloft and Effexor.

On Sept. 14, the Food and Drug Administration's medical advisory group decided that antidepressants should come with a warning that they can spur suicidal behavior in children and teenagers.

The lawsuit alleges that Pfizer Inc. "failed to adequately test, evaluate and otherwise study the pediatric effects of Zoloft before marketing it to the public."

Spokeswomen for Children's Hospital and Immanuel Medical Center said their hospitals' attorneys had not seen the lawsuit and they would not immediately comment. Officials at Pfizer did not return a telephone call Wednesday seeking comment.

A spokesman for Wyeth, Lowell Weiner, said the company had not seen the lawsuit. However, Weiner said, Effexor is not recommended for use with pediatric patients.

Also named as defendants are Sharon S. Cannon, Ph.D., and Dr. Michelle M. Cassidy of Children's Hospital; and Dr. Michael L. Coy of Alegent Health-Immanuel Medical Center.

None of the defendants warned that "Jacob should be watched closely for signs that his condition was getting worse," the lawsuit said.

The lawsuit, filed by attorney Andrew J. Hilger, said Jacob began taking Zoloft on Sept. 9, 2002, on Cannon's recommendation.

Jacob's behavior worsened to include intensified agitation and suicidal desires, the lawsuit said.

Jacob's Zoloft dosage was increased three times between Sept. 17 and Oct. 2 on the recommendations of Cannon, Cassidy and Coy, the lawsuit said. On or about Oct. 8, Cassidy advised gradual decrease of the Zoloft dosage and prescribed the drug Effexor, the lawsuit said.

Two days later, Jacob was found dead in his parents' basement.

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?

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.

Feds Warn on Children and Antidepressants

Mon, 13 Sep 2004 00:00:00 -0700

Tom Woodward's 17-year-old daughter Julie committed suicide by hanging herself. He blamed the antidepressant that the teen had been taking for seven days.

"We are certain that Zoloft killed our daughter," said Woodward, one of more than 70 speakers enveloping federal health advisers Monday in an outpouring of emotion, tears and anger.

Others witnesses, like Cynthia Wainscott, urged the Food and Drug Administration not to take away drugs that have reduced suicide rates among depressed youths.

Two FDA advisory panels are considering whether agency action including stronger warning labels is needed on antidepressants because they have been linked to suicidal tendencies among children who take them. The joint panel will weigh the benefits of nine drugs given to depressed children against the risk that the remedies may increase suicidal thoughts and actions.

"Drug companies have purposely deceived the public about the safety and efficacy of their drugs," Woodward said, calling for a strong, black warning on packaging for popular antidepressants.

Susan Bro, spokesman for Zoloft manufacturer Pfizer, would not comment on Woodward's allegations because of pending litigation. Zoloft, she said, is a "safe and effective drug when used as prescribed."

Wainscott showed panel members a photograph of her granddaughter Jessi, who she said began suffering from depression at age 11. Now 15 and on medication, Jessi has returned to her normal self, her grandmother said.

"Tell them not to do anything that will make people afraid to go for help," Wainscott said Jessi told her. Wainscott, chair of the National Mental Health Association, quoted her granddaughter as saying antidepressants meant "there are no invisible strings pulling me down."

Tarek Hammad, an FDA senior medical reviewer, told the panel an additional 2 percent to 3 percent of children are likely to incur increased suicidal thoughts from taking any antidepressant

He told reporters that looking at all the drug company studies created a complete picture. "Then, you can see significant findings," Hammad said.

Relative risks of suicidal behavior or thoughts were highest among youths taking Luvox, Effexor and Paxil and lower among youths taking Celexa, Zoloft and Prozac.

Untreated depression is a serious illness that threatens the children's lives, said Dr. Laurence Greenhill, speaking on behalf of the American Academy of Child and Adolescent Psychiatry, which represents 7,000 child psychiatrists. He said he found it reassuring that the FDA's detailed analysis did not find a single completed suicide among 4,440 depressed youth in drug company-sponsored clinical trials.

Parents whose children are locked up in prison, prematurely dead or survivors of attacks by rampaging teens on antidepressants wore T-shirts and pins and carried photographs of their lost loved ones.

"Where were you when I got shot?" demanded Mark Taylor, 21, who survived multiple gunshots fired by the Columbine High School attackers, including one teenage gunman who had been taking an antidepressant.

"As Americans, we should have the right to feel safe. And, if you were doing your jobs, we would be safe," Taylor said.

FDA epidemiologist Andrew Mosholder, who pushed for the closer look at suicidal behavior among children taking antidepressants, noted a clustering of serious events involving suicide within the first four days after youths discontinued Paxil treatment.

Mosholder was praised by grieving family members for requesting clarification last year from Paxil manufacturer GlaxoSmithKline. The data he received in May 2003 suggested a link between Paxil and increased suicidal acts among children taking it.

Dr. Robert Temple, director of the FDA's office of drug evaluation, told reporters he had no regrets delaying the testimony at a previous hearing because he still thinks Mosholder's data may be flawed.

Temple said it was "interesting and persuasive" that studies link all antidepressants to heightened suicidal thoughts and actions among youth. "They all lean the same way, including Prozac now," he said.

In about one-quarter of 200 studies on about 100 pharmaceutical products, the FDA changed the dosages for children, found new adverse reactions that occurred only among children or found the drugs didn't work in kids at all.

Strong Warnings Expected On Antidepressants For Kids

Wed, 08 Sep 2004 00:00:00 -0700

Scientific advisers to the Food and Drug Administration next week are expected to recommend tougher warning labels or other restrictions on antidepressants linked to suicidal behavior in children.

More than 1 million U.S. children take the pills. A re-analysis of studies, released last month, confirmed that those on antidepressants may be nearly twice as likely to become suicidal as kids given sugar pills, and some drugs appear to raise the risk much more than others.

There were no suicides in the 4,250 children studied, but experts think a "wait and see" approach isn't likely.

"They're going to have to do something," says Graham Emslie, child and adolescent psychiatrist at University of Texas Southwestern Medical Center in Dallas. "The horror stories have been just too horrible, and their advisory committee is going to be influenced."

Dozens of parents testified at a February FDA hearing that antidepressants had caused their children to kill themselves. Similar testimony is expected at the hearings in Bethesda, Md., starting Monday. The following day, the FDA's advisory panel may recommend new labeling. The agency usually, but not always, does what its scientific advisers suggest.

In March, the FDA put stronger warning labels on 10 antidepressants after its expert panel recommended the step. But critics 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.

Prozac is the only FDA-approved drug for childhood depression among a newer class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). Other SSRIs, such as Zoloft and Celexa, haven't been proven safe or effective in depressed kids. They are approved for adults and can still be legally prescribed, off-label, to children.

After March, there was a sharp drop in pediatric users of antidepressants, according to an analysis for USA TODAY by Medco, a large pharmaceutical benefit management firm. Records show a 10% decline in patients under 18 taking the drugs in the three months after the March warnings, says spokeswoman Jennifer Leone.

Still, "the data are not black and white" on whether the drugs can make kids more suicidal, says a memo sent last month to the FDA advisory panel by Thomas Laughren, the agency's team leader for psychiatric drugs. But risky signals have been raised for some drugs in some studies, Laughren says.

The FDA, like the British, could advise doctors to prescribe no antidepressants, with the exception of Prozac, for kids. That's possible, but viewed as unlikely. The agency also could put a "black box" warning on a few of the drugs, a much stronger warning than the agency called for in March. This step is seen as somewhat more likely.

Tougher label warnings might add the fact that "after clinical trials," all of the drugs (except Prozac) haven't been found to work for kids. Since most drugs haven't been studied in children, "pediatricians assume, in the absence of data, the drug just hasn't been studied. This would tell them it has, and hasn't been found to work," says University of Pennsylvania pediatrician Robert Nelson, an advisory panel member.

The FDA also might send out new "Dear Dr." letters confirming a suicidal risk the March advisory said no risk had been proven or require pharmacists to give sheets warning of possible suicidal behavior to every adult picking up a child's prescription.

Regulating the drug has been tricky because major depression increases the risk of childhood suicide about 12-fold. In studies of children who killed themselves, most weren't on medication, says psychiatrist Frederick Goodwin of George Washington University.

But in real-life medical practice, kids with minor adjustment problems too often get antidepressants, some psychiatrists say. And many doctors say the drugs occasionally trigger a frenzied, impulsive agitation that can lead to suicide.

There's rising concern about kids with undiagnosed bipolar disorder (manic-depression) on antidepressants because doctors think they have ordinary depression. Studies suggest up to half of teens with major depression symptoms are manic-depressives, and most with pre-puberty depression become bipolar, Goodwin says. In these kids, SSRIs can trigger suicidal mania. Goodwin thinks the FDA should warn doctors to ask about signs of future bipolar disease mood swings, impulsiveness, aggression before prescribing antidepressants.

Phyllis Day of Boca Raton, Fla., wishes her 9-year-old daughter, Hallie, hadn't been put on Zoloft a year and a half ago. "She became angrier, more openly violent and suicidal," Day says. One particularly scary time, the little girl struggled to pull her hand out of her mother's so that she could run into heavy traffic.

She was taken off the drug after several months and diagnosed as bipolar a few months later. Now on different medication, Hallie is much improved, Day says. "We're very unhappy that doctors are giving Zoloft to kids who are bipolar. It was a nightmare."

It's a serious challenge for the FDA to weigh the potential benefits of antidepressants for kids against risks because there is relatively little research on each drug, experts say, and emotions run so high. About all everyone can agree on is that the FDA is likely to be criticized no matter what it does.

Anti-Depressant Deaths Increase

Fri, 20 Aug 2004 00:00:00 -0700

Between 1993 and 2002, 118 people in England and Wales taking venlafaxine (Efexor) died, 17.6 deaths per million prescriptions.

Although the rate is still lower than that associated with old-generation tricyclic drugs, it is rising, while the rate for tricyclics is falling.

The figures were collected by the National Audit Office.

Overall, there were 4,767 antidepressant-related deaths in England and Wales in the decade studied.

Nearly eight out of every 10 of these were suicides.

Tricyclic antidepressants made up the bulk of the cases, linked to nearly 4,000 deaths, or 43.1 deaths for every million prescriptions.

But venlafaxine, from the selective noradrenaline reuptake inhibitor (SNRI) drug family, overtook another class of newer antidepressants that includes drugs like Prozac (fluoxetine) and Seroxat (paroxetine) the selective serotonin reuptake inhibitors (SSRIs).

SSRIs were linked to 310 deaths overall, but the rate was only 4.3 deaths per million prescriptions.

Since it was launched in 1995, prescriptions of venlafaxine have reached 3.2 million over the last 12 months, earning the manufacturer Wyeth 125 million per year.

A spokeswoman from Wyeth said the statistics did not compare like with like.

"They do not take into account the severity of the condition of people being treated, or the fact that patients being given Efexor have often failed on other antidepressants.

"The patients are often more seriously ill with depression and that is why the figures are higher," she said.

Monitoring

Sophie Corlett, director of policy at Mind said because Efexor was a relatively new antidepressant, reports of adverse side effects had only begun to emerge recently.

"Mind has been aware for some time of reports from mental health service users of quite debilitating side effects ranging from dizziness and nausea to severe headaches and dependency problems.

"Although, on the whole, Efexor has a better reputation than other antidepressants, in a recent survey almost half of respondents reported difficulties when coming off the drug or in reducing its dose.

She said questions remained over the links between certain antidepressants and possible increased suicidal feelings.

"It is therefore vital both that alternative non-drug therapies are explored for less serious cases of depression and that where drug treatment is the only realistic option, that those drugs are rigorously tested and regulated."

But she added: "Anyone taking antidepressants who has concerns should consult their doctor. On no account should they simply stop taking the medicine."

A spokeswoman from the Department of Health said the Committee on Safety of Medicines and its expert working group on SSRIs was reviewing the data relating to the safety and efficacy of venlafaxine as part of its ongoing work.

"SSRIs are known to be safer in overdose than the older tricyclic class of antidepressants," she said.

The National Institute for Clinical Excellence is also soon due to produce guidelines on the treatment of depression and anxiety in adults in October of this year.

Teen Suicide Risk Increased by Antidepressants

Wed, 18 Aug 2004 00:00:00 -0700

A new warning by the Food and Drug Administration says taking antidepressant drugs increases a teen's risk of suicide.

And this time, the FDA has come under fire for allegedly withholding information about the risks, from the American public.

The latest FDA study reveals that during the first month of antidepressant treatment, kids are almost twice as likely to have suicidal thoughts.

David Feinberg, M.D., UCLA Psychiatric Medical Director, said, "It's the first month or so of treatment where children taking this medication can have a new onset of suicidal ideation. So during that time, they need to be followed closely."

The Wall Street Journal estimates that roughly five million American children are now taking antidepressant drugs. And with doctors writing three times as many prescriptions as they did 10 years ago, and millions of kids on one of the nine popular antidepressants studied, parents have cause for concern.

Thomas Woodward's daughter took her life seven days after she started taking Zoloft. Woodward said, "We were told how mild and safe these drugs were, and essential to her getting better."

Jame Tierney took the antidepressant, Effexor to relieve her migraine headaches, and she developed suicidal tendencies.

"I had a lot of suicidal thoughts," Tierney said, "and I thought I wanted to die."

By last February, the FDA knew that antidepressants increase suicidal events in kids under 18.
But instead of publicizing the new information, the agency opted for drug warning labels and additional studies.

Now it faces two congressional investigations. And a growing list of angry parents.

Woodward said, "Our daughter would not have done this if it hadn't been for the drug, and I'm convinced about that."

Jame's mother, Jennifer Tierney, commented, "The FDA is not doing its job to protect our children. How pathetic is that?"

"I think it's been handled abominably,' remarked Dr. Joseph Glenmullen of Harvard Medical School. "The FDA has just dragged its feet and delayed this whole thing. It's an outrage."

Still, psychiatrists say some depressed youngsters benefit from the drugs. This leaves parents and care givers searching for the best way to safely treat the growing number of American children diagnosed with this potentially fatal disease.

Women Warned Over Antidepressants

Tue, 10 Aug 2004 00:00:00 -0700

Pregnant women should avoid taking a broad range of antidepressants and smoking-cessation medications because the drugs may cause their newborn babies to suffer serious side effects, ranging from respiratory problems to constant crying, Health Canada is warning.

In an advisory posted yesterday on its website, Health Canada said the danger is greatest when women take the drugs, in particular a newer class of antidepressants known as SSRIs, during the third trimester of pregnancy.

The regulatory agency said newborns whose mothers took the medications "can experience drug withdrawal symptoms or toxicity after delivery."

The effects are wide-ranging, though the most common symptoms include respiratory problems, trouble eating, seizures, body rigidity, irritability, jitteriness and constant crying. In some cases, Health Canada warned, newborns may require tube feeding or breathing support, but said the symptoms appear to be reversible.

According to U.S. research, 10 to 15 per cent of pregnant women suffer from depression, but it is unclear how many are treated with antidepressants.

In the advisory, eight drugs were singled out as being of concern: bupropion, which is sold under the brand names Wellbutrin and Zyban, is prescribed both as an antidepressant and a smoking-cessation treatment. Both are products of GlaxoSmithKline and marketed in Canada by Biovail Corp.; citalopram, sold under the brand name Celexa, marketed by Forest Laboratories;fluoxetine, which is better known as Prozac, a product of Eli Lilly; fluvoxamine, sold under the brand name Luvox by Solvay; mirtazapine, sold under the brand name Remeron, marketed by Akzo Nobel; paroxetine, which is commonly known as Paxil, a product of GlaxoSmithKline; sertraline, sold under the brand name Zoloft, marketed by Pfizer; venlafaxine, best known as the drug Effexor, a product of Wyeth-Ayerst Laboratories.

Several of the drugs are selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants that has been in the news a lot lately because of research suggesting they increase suicidal thoughts in children and adolescents, and reports that pharmaceutical companies withheld data showing the negative impact of these drugs.

In its advisory, Health Canada said: "If a woman is pregnant and is taking an SSRI, or other newer anti-depressant, she should discuss the risks and benefits of the various treatment options with her health-care professional. It is very important that patients do not stop taking these medications without first consulting with their doctor."

The health regulator said it will also ask manufacturers to provide stronger warnings on the labels of drugs.

Wende Wood, a psychiatric pharmacist at the Centre for Addiction and Mental Health in Toronto, said the warning has to be taken in context. "There is a risk from these drugs, but we have to balance that against not being treated for depression during pregnancy and for post-partum depression."

She said that women who are depressed eat poorly and tend to self-medicate with tobacco, alcohol and non-prescription drugs, all of which can cause far more severe damage to the fetus.

The new Health Canada advisory is similar to one issued in June by the U.S. Food and Drug Administration.

There, an expert panel studying the safety of SSRIs said it had received hundreds of reports of adverse effects in newborns. The scientists said they did not have enough data to understand precisely how the drugs affect newborns, but their use should be limited as a precautionary measure.

The expert panel cautioned, however, that depression itself in an expectant mother can have negative effects on the baby.

Since evidence arose about the effects of SSRIs on newborns, many physicians have had pregnant women slowly decrease the dose of antidepressant or stop completely to minimize drug withdrawal symptoms in the newborn baby.

Dr. Wood said that is not necessarily a sound approach. "We don't know if this is dose related," she said.

Earlier this year, the U.S. Food and Drug Administration ordered the manufacturers of 10 big-selling antidepressants to alter their labels to warn of a possible increase in suicidal thoughts and behaviours by people taking these prescription drugs.

Health Canada followed suit, issuing its own public health warning about seven SSRIs, excluding Prozac.

Drug Leads To Sons Suicide, Family Says

Tue, 10 Aug 2004 00:00:00 -0700

Had she known in May what she knows know, Wanda Custance said she might have been able to save the life of her scholar-athlete son.

Hoping to spare other families a tragedy like their own, Wanda and Gary Custance urge relatives to frequently check in with loved ones who are taking anti-depressants.

"People who are prescribed these drugs, they really have to be monitored closely," she said. "I felt I wasnt all that aware, other than I didnt like the idea of him taking it."

Perry Custance, a 22-year-old senior at Oregon Institute of Technology, had been a distance runner from South Medford High School, and held the schools records in the 1,500- and 3,000-meter run. He also was the all-American scholar-athlete honor at OIT in 2003.

Wanda said she knew her son was prescribed the anti-depressant Lexapro around the first of April after he sought treatment for a side ache and lower back pain. Perry took the medication until June.

"We think he stopped taking it probably around the third or fourth (of June)," his mother said. And then it was the weekend of June 12 that Perry died of an apparent self-inflicted gunshot wound near his family home outside Ruch.

"His friends had said hed gotten really, really down about a week before the suicide," she said, adding that his handwritten class notes were illegible during that time.

Because Perry was an adult, his medical records are not available to his parents. But as far as they knew, their son was not depressed.

Lexapro is approved for the treatment of anxiety and major depression, and no other medical uses are listed on the manufacturers Web site. The site warns that discontinuing the medication against a doctors advice might worsen depression or anxiety symptoms.

Newer anti-depressants such as Lexapro, known as selective serotonin reuptake inhibitors (SSRIs), have come under recent scrutiny.

In March, the Food and Drug Administration asked makers of SSRIs to include warnings that children and adults might become more depressed or suicidal while taking them, and close supervision particularly at the start of treatment is required.

The affected drugs include Prozac, Zoloft, Paxil, Luvox, Celexa, Lexapro, Wellbutrin, Effexor, Serzone and Remeron. More information is available at www.fda.gov on the Web.

Gary Custance wishes he had known about the warning.

"I would have liked to have seen a warning label on the bottle," he said.

Gary Custance said his sons May 12 prescription bottle had no such warning.

The warnings are included in the drugs package insert, according to an Oregon Health & Sciences University specialist.

James Hancey, assistant professor of psychiatry at OHSU, said upon hearing the familys story, he doesnt think the medication caused Perry to take his own life.

"Too often people will start to feel better, then decide they dont need their medications any more, and they stop them," he said. "Because he went off the medication, the depression returned."

Hancey said medical literature for Lexapro does not suggest any correlation between stopping the medication, time passing, and then a suicide occurring.

"It was more likely a return of the underlying major depressive symptoms," he said.

He said that by and large, the anti-depressants end up saving lives although theres no way to track the number of prevented suicides.

But Perrys father doesnt buy it.

Gary Custance doesnt believe his son would have ended his life had he never taken Lexapro, but once he was on it, he should have stayed on it.

"Theres a serious problem with coming down from this stuff," he said, adding that his son should have had more intensive medical supervision. "They didnt monitor it like they should have."

Wanda Custance said questions that remain unanswered make her sons death more painful.

"I dont want to see anybody go through this," she said.

Depression Drugs Linked To Suicides In Teens

Mon, 09 Aug 2004 00:00:00 -0700

At least five teenagers in Canada have died, four by suicide, while being treated with the most widely prescribed antidepressants in Canada and at least 100 other children as young as 18 months old have experienced adverse reactions to the pills, CanWest News Service has learned.

The most recent reported suicide involves a 14-year-old boy who killed himself after being on Paxil, one of the antidepressants known as selective serotonin reuptake inhibitors (SSRIs), for 25 days.

Health Canada was notified of the boy's suicide on July 22, 2003, nearly two weeks after the government and GlaxoSmithKline, the makers of Paxil, warned doctors not to prescribe the drug to children and teens because of a possible increased risk of suicidal thinking, suicide attempts or self-harm. Health Canada learned in October 1996 of a 17-year-old boy who committed suicide while he was being treated with Zoloft. A suicide involving an 18-year-old boy who had been taking Prozac was reported to the government in 1992.

In all three suicides, the antidepressants may have contributed to the deaths, according to adverse drug reaction reports contained in an edited, online Health Canada database. It's estimated only one to 10 per cent of all adverse drug reactions are reported to Health Canada.

But there's no proof of a cause-and-effect link between the antidepressants and any of the suicides, and it's not known from the reports whether any of the youth had a history of suicide attempts, or what they were being treated for.

"Health Canada did conduct an assessment to see whether the deaths were caused by SSRIs," said department spokeswoman Jirini Vlk. "There was no causal link established."

The fourth suicide involved an 18-year-old girl who overdosed on Effexor; her death was reported to Health Canada in December 1998. The fifth death involved a 16-year-old boy who died of cardiomyopathy, inflammation of the heart, after taking Celexa for 17 days. It is not known from the report, received in May 2003, how long the teen had cardiomyopathy. The youth had also been taking another antidepressant, and possibly an anti-psychotic drug when he died.

According to the doctor who filed the report, Celexa "may be contributory" to the death.

The antidepressants are at the centre of a growing storm over whether SSRIs, blockbuster drugs that have become among the most popular medicines in history, may cause some children to become suicidal or trigger other severe emotional or behavioural changes within weeks of treatment starting or a change in dose.

New York State Attorney General Eliot Spitzer last week launched a lawsuit against GlaxoSmithKline, alleging the drug giant "engaged in repeated and persistent fraud" by concealing critical scientific studies about the safety and efficacy of Paxil for depression in children and adolescents, a charge the company denies. "All pediatric studies have been made available to the FDA (U.S. Food and Drug Administration) and regulatory agencies worldwide. We have publicly communicated data from all pediatric studies," the company said.

Today, preschoolers make up the fastest growing segment of the SSRI market, studies show. Even infants under one are being prescribed the drugs for anxiety or sleeping problems.

Health Canada records reveal the government began receiving reports of agitation, hostility, aggression, hallucinations, psychotic states, impulsive behaviour, paranoid reactions and other suspected drug reactions in children on SSRIs at least five years ago.

Yet a public advisory warning parents to rigorously watch their children for signs of unusual or disturbing behaviour, including wanting to harm themselves or others, wasn't issued until last week. And while British authorities ordered doctors six months ago to stop prescribing the antidepressants to anyone under 18, Health Canada has decided against barring their use in children or restricting their use to trained doctors who have the time to do a proper assessment and follow-up, even though none of the drugs have ever been approved for use in children in Canada.

A recent analysis by Health Canada of all adverse reactions experienced by patients taking SSRIs found no direct link between the drugs and incidents of death.

Critics say the story of how SSRIs have become among the top drugs prescribed to children is a saga of biased reporting, bureaucratic breakdowns and flawed assumptions that what would work in adults would work in children, a "disaster," the world's top medical journal The Lancet says, that has led to spiralling prescriptions for SSRIs for toddlers, grade-schoolers and adolescents without any evidence most of them work much better than placebos, or fake pills.

Some parents swear the medications gave their children full, happy and functional lives. Medical groups such as the American Psychiatric Association fear the controversy will scare doctors away from prescribing the drugs or keep people who need help from getting treatment.

But critics, including some of Canada's leading child psychiatrists, worry the antidepressants are being handed out like candy, and that their soaring use reflects our busy society's growing intolerance for moodiness, shyness, anxiety and other normal life problems in children.

Suicide By Kids Sparks Hearing

Thu, 05 Aug 2004 00:00:00 -0700

Doctors told Dominique Slater's parents that their teenage daughter might become nauseated or gain weight from pills prescribed to battle depression.

But the 14-year-old Newman girl became irritable, hostile and aggressive side effects of anti-depressant drugs that her parents now say led to her suicide.

After Dominique's body was found April 14, 2003, in the Delta Mendota Canal in Patterson, her family was motivated to raise awareness about the potentially lethal link between anti-depressant drugs and teen suicide.

"Our obligation is to speak out so another family doesn't have to go through this nightmare," Lorraine Slater, Dominique's mother, said before a hearing Wednesday at the state Capitol.

She also testified before a federal Food and Drug Administration hearing in February. A month later, the FDA issued a warning that 10 anti-depressant drugs might worsen depression or suicidal tendencies. Dominique had taken three of the 10 drugs cited in the advisory.

Wednesday, as Dominique's brother Jonathan, 14, held framed family photos, her father, Robert, said anti-depressant drugs have not been proven safe for adolescents, who are being used as a "test market."

"I'm focusing on what we can do to avoid tragedies," said Sen. Tom Torlakson, D-Antioch, who called for the hearing before the Senate Health and Human Services Committee. His 21-year-old niece committed suicide earlier this year shortly after taking an anti-depressant drug.

"The FDA's warning came out a week after her suicide," Torlakson said.

Although England in December effectively banned six of the same drugs from use by children, no one on the panel Wednesday called for a similar ban, instead focusing efforts on more research to find out short-term and long-term effects of the drugs.

There also is a push to require patients to sign a waiver that explains the potential side effects, something already done for the drug Accutane, used to treat acne but linked to causing depression among teens.

"Family doctors now write 70 percent of prescriptions for anti-depressants and know little or nothing about this side effect," said Dr. Joseph Glenmullen, clinical instructor at Harvard Medical School and author of "Prozac Backlash," who spoke at the hearing.

He said doctors mistakenly think depression is getting worse and increase the dosage of the drug, possibly doing more damage.

Glenmullen added that drug companies have been dishonest about their research. He compared the industry with Big Tobacco, which he said spent years denying side effects, discrediting doctors, funding "junk science" by industry-friendly doctors and blocking needed research.

In June, New York Attorney General Elliot Spitzer filed a lawsuit against GlaxoSmithKline, maker of the anti-depressant Paxil, for concealing unpublished data.

The company had denied the charge.

In July, GlaxoSmithKline sent a letter to doctors advising that the drug not be used to treat children because of a "possible risk of suicide." In August, the maker of Effexor, Wyeth, sent a similar letter to physicians.

Drug company representatives were not included at Wednesday's hearing. But Carlo Michelotti, chief executive officer of the California Pharmacists' Association, told lawmakers that anti-depressant drugs are growing in popularity "because they work."

Child Advocates Fear Drug Perils

Sun, 20 Jun 2004 00:00:00 -0700

More information on Serzone side effects
More information on Paxil side effects

For years, attorneys who represent children, along with parents and some legislators, have said that too many juvenile offenders in the state's custody are prescribed potentially dangerous antidepressants and other mental health drugs.

Children's advocates say they fear some youths are medicated to make them more docile and easily controlled while in Department of Juvenile Justice programs.

Their concerns were heightened in March when the federal Food and Drug Administration asked manufacturers of Prozac, Zoloft, Paxil, Effexor, Serzone, Wellbutrin and other antidepressants to include a warning label stating that children taking the drugs should be watched closely for suicidal tendencies.

The Department of Juvenile Justice did not issue advisories to make their program operators, guards and medical professionals aware of the increased risk of suicide linked to the antidepressants, even though 80 children have attempted suicide within the department this year.

Department spokeswoman Catherine Arnold said the child's physician or the program's licensed medical provider is responsible for weighing FDA pronouncements.

But some critics contend that the department needs to take a greater role in evaluating whether children in its custody are properly diagnosed, treated and monitored for adverse side effects.

A strict policy proposed within the department in early 2003 to better regulate the administration of psychotropic drugs was never fully implemented. Records show that department leaders received complaints from program providers that the policy was too burdensome and costly.

On any given day, the Department of Juvenile Justice does not know how many of the roughly 8,500 children in the state's more than 150 detention and residential programs are on prescription drugs for mental illness, department spokesman Bob Finch said. That information, he said, is kept in each child's medical file but not reported to Tallahassee.

The only study that has been done indicates the number could be large. Nearly half of the 1,031 girls and 21 percent of the 5,278 boys in residential programs were taking some sort of mind-altering prescription between November 2002 and April 2003, the department reported in a federally funded review. It did not look at the state's detention centers.

Broward Juvenile Court Judge Larry Seidlin said some young offenders write to him, saying they don't want to be on psychotropic drugs. Seidlin said he sets up hearings to review their concerns. Some of the youths, he said, appear "sort of in a semi-coma."

Dr. Robert Wray, psychiatrist at the Arthur G. Dozier School for Boys and Jackson Juvenile Offender Correctional Center in Marianna west of Tallahassee, two Department of Juvenile Justice programs for 1,000 teenage boys, agrees that too many children within the department are put on psychotropics.

"Unlike many of the DJJ facilities I hear about, our facility here is very conservative," Wray said. "For literally 15 years, we've been, at first, routinely taking all boys off all psychotropics when they come in. Now we just have a philosophy of me seeing them first before we discontinue the medication. But we almost always discontinue."

Wray said most of the boys they observe were prescribed medications without a proper diagnosis. "As far as we're concerned, the use of psychotropics in the community is grossly abused," he said.

Among those calling for greater accountability is state Rep. Walter "Skip" Campbell, a Tamarac Democrat who has pushed the Department of Children & Families, which provides foster care, to address the same issue.

"It seems the same questions we have asked of DCF should be asked of DJJ," Campbell said. "Because you don't want to overmedicate these kids to the point they become zombies and to the point that they have suicidal events."

In November, DCF Secretary Jerry Regier told a Senate committee that one of every 10 children in DCF custody about 5,100 kids are on drugs to treat depression, schizophrenia and other mental illnesses. About 550 children age 5 and younger were prescribed potent medications such as Valium and Ritalin.

In response to the FDA warning, DCF sent an alert to its mental health and child welfare staff. The department also set up a "MedConsult" hotline through the University of Florida's College of Medicine to provide free advice on psychotropic medications to physicians, judges, caseworkers and foster parents.

Legislators this spring, however, turned down bills that would have authorized the University of Florida to create a Center for Juvenile Psychotropic Studies that would collect and track information on how many juvenile delinquents and foster children are prescribed psychotropics.

"All we were trying to do was gather what we considered was accurate information to be able to come up with good public policy," said Ocala Republican Rep. Larry Cretul, the legislation's sponsor in the House. A companion piece in the Senate also stalled.

Cretul said some legislators objected to amendments that prohibited school personnel from recommending psychotropics for children and DCF and DJJ officials worried that the bill would pose added costs to the agencies to collect the desired information.

Cretul said the Department of Juvenile Justice's lack of accountability from its contractors is "somewhat scary."

A strict policy for psychotropic drug use that the department considered implementing in the winter of 2003 would have required operators of detention centers and residential programs to monitor the dosage and side effects of drugs regularly, justify the use of one or more drugs in writing, obtain written permission from parent, and inform parents over the phone by a physician of the benefits and risks of the medication.

The potential side effects of psychotropic drugs, according to the aborted medication policy, include in part: depression, tremors, irritability, increased appetite, anxiety, slurred speech, drooling, vision problems, chest pain, crying and hallucinations.

Records available through the department's Web site show that the proposed regulations generated widespread complaints from some operators of the state's juvenile lockups. Among their objections: it would be too costly and cumbersome to force doctors to call parents.

"Our contracted medical professionals have already informed us that this responsibility is not a requirement and that they do not have the time to make all these calls (and in several instances have told us they won't do it)," Peter Plant, a vice president of Securicor New Century, a private juvenile corrections company that contracts with the state, wrote in response to the department's solicitation for public comments. "Even if they agreed, the additional costs would be considerable."

4 Antidepressants A Danger To Kids, British Study Says

Sat, 01 May 2004 00:00:00 -0700

Four popular antidepressants being used to treat thousands of depressed American children are unsafe, ineffective or both, according to the first careful scientific review to include all available studies, including negative data that has long been withheld from public scrutiny by the pharmaceutical industry.

It is especially dangerous to prescribe Paxil, Zoloft, Effexor and Celexa for children who are suicidal, said British researchers who conducted the analysis published in the journal the Lancet, because the data shows an increased of suicidal behavior among children taking the drugs and no benefit.

The study calls into question repeated assurances of the American psychiatric establishment, which has regularly encouraged use of the medicines in depressed children. It also contrasts sharply with the position of the U.S. Food and Drug Administration, which has had access to the data but has not identified such problems.

The analysis involved no new data, but it is the first scientific analysis of all available trials to be published in a peer-reviewed journal. As such, it puts the scientific debate over the medicines on a new footing and deepens the chasm between the predominantly positive American view of the drugs and a growing stream of negative reviews by Australian, Canadian and British psychiatrists. The Lancet analysis backs up the warning by British regulators last year not to prescribe the medicines to depressed children.

In a sharply worded editorial, the Lancet's editors said the trust of patients had been abused by doctors and the pharmaceutical industry and that safety had been compromised in the search for profits. The state of the research, the editorial concluded, is riddled with "confusion, manipulation and institutional failure."

"If I wanted to introduce a new drug for children who are suicidal and said this has very little proof of efficacy and it has an increased risk of suicide, people would say I was mad," said Tim Kendall, director of the National Collaborating Center for Mental Health in London and one of the authors of the new study.

Yet, Kendall said, that is precisely the situation with the four drugs. Kendall's analysis, which was funded by the British government, contrasted the largely positive results of studies published by drug manufacturers with negative data that the companies call proprietary and have not published. British regulators recently made the unpublished data available for study.

"In each of the published articles, the authors concluded the drug was either effective or safe or both," Kendall said. "When you look at the combined evidence, it is ineffective, unsafe or both."

The review found a positive risk-benefit ratio for only one medicine Prozac, which the researchers said did not carry an elevated risk of suicide and had been proven to benefit depressed children. The article said that while the other antidepressants should not be given to children with depression, it is possible that children with anxiety or other disorders might benefit from them. The number of American children being treated for depression in any year has surged in recent years; a majority are being treated with antidepressants.

The U.S. Food and Drug Administration said it was continuing to evaluate whether the antidepressant trials showed an increased risk of suicidal behavior. Although an internal FDA analysis found an increased risk of suicidal behavior among children taking the drugs, senior officials at the agency have said they do not have confidence in the conclusion.

The matter has been referred to a team at Columbia University for further evaluation.

"Some of the things called suicidal thinking or behavior are not," said Robert Temple, the FDA's associate director of medical policy, in a recent interview. "There is one child banging her head against the wall that is not suicide. There are quite a few children who did superficial cutting. That doesn't show intent to kill oneself."

FDA officials have consistently said that the large number of failed antidepressant trials do not prove that the drugs are worthless, a position in direct conflict with the authors of the Lancet study.

Mariann Caprino, a spokeswoman for Pfizer Inc., which makes Zoloft, categorically rejected the charge that the company had compromised the safety of children in the pursuit of profits.

"The use in children of our drug in particular, is a very, very, very small percentage of the overall total prescriptions of this product," she said. "To suggest that we are motivated by profiting off of children is ludicrous."

While Caprino said all the company's data had been disclosed, the Lancet article said a published study that combined two Zoloft trials omitted information that, when factored in, showed an "unfavorable risk-benefit balance."

Wayne Blackmon, a Washington psychiatrist who has long said that clinicians cannot rely on the integrity of the data they are being given, said Congress should force the FDA to take unpublished negative trials into account and force the companies to make all data available for public scrutiny.

FDA Was Urged To Limit Kids' Antidepressants

Fri, 16 Apr 2004 00:00:00 -0700

A medical reviewer at the Food and Drug Administration recommended earlier this year that the agency adopt a tough "risk management strategy" urging doctors to stop prescribing most antidepressants to children, but the FDA rejected his advice and instead asked drug companies only to warn patients and doctors about possible risks to young patients, The Chronicle has learned.

Dr. Andrew Mosholder, an epidemiologist in the FDA's Office of Drug Safety, analyzed 22 clinical trials of nine antidepressants and concluded that the drugs appeared to double the risk of suicidal behavior among children. A copy of his report, obtained by The Chronicle, shows that Mosholder recommended that the FDA adopt a "risk management strategy directed at discouraging off-label pediatric use of antidepressants" other than Prozac in the treatment of children with depression.

As reported by The Chronicle at the time, Mosholder's presentation to an FDA advisory committee in February was removed from the agenda by his superiors at the agency.

The FDA opted not to issue a recommendation to doctors that they stop prescribing the drugs to children, as British regulators did last year and as Mosholder had urged. Instead, the agency took a much milder step last month and called on drug companies to include warnings in the prescribing information provided to doctors about the risks of negative side effects among patients who start taking a drug or increase its dosage.

The agency also contracted with a group of doctors at Columbia University to reanalyze the clinical trial data provided by drug companies, the same data Mosholder reviewed, to see whether suicidal events were correctly classified. Agency officials have argued that the data from those trials are sometimes vague and that some behaviors such as a child slapping herself in the head may have been labeled wrongly as suicidal events by researchers conducting the drug company-funded studies.

Committees in both the House and Senate have opened investigations into the withholding of Mosholder's report and into efforts by the FDA's Office of Internal Affairs to identify the staff members who leaked information to The Chronicle.

One congressional source predicted that the investigation was likely to trigger congressional hearings. "I think eventually there will be some hearings," the source said. "There's no way to put a good face on this decision not to allow Dr. Mosholder to present his conclusions to the advisory committee."

Despite repeated requests, senior FDA officials declined to comment for this story.

However, in a letter sent Wednesday to House Energy and Commerce Committee Chairman Joe Barton, R-Texas, an agency representative defended the agency's decision to keep Mosholder from presenting his report. Agency officials "decided that having Dr. Mosholder present his conclusion to the Advisory Committee, with the appearance that it was an agency determination, would be potentially harmful to public health as it might lead patients who were actually benefiting from the use of these drugs to inappropriately discontinue therapy," wrote Amit Sachdev, acting associate commissioner for legislation.

Critics of the FDA's handling of the antidepressant ruling reacted to details of the Mosholder report with outrage. "It's astounding that FDA officials actively blocked vital, possibly life-saving information about the suicide risks to children" of these drugs, said Vera Sharav, president of the Alliance for Human Research Protection, an advocacy group. "Every day that doctors and parents are not informed about the risks, children are at risk of dying."

In arguing that the agency should take strong action rather than wait for the reanalysis by the Columbia University group, Mosholder made much the same point in his report.

"Given the strength of the association shown by the present data, the clinical importance of the apparent effect, and the fact that the additional analyses are likely to take several more months to complete while considerable numbers of pediatric patients are being exposed to these drugs, I favor an interim risk management plan," he wrote.

Mosholder's report found that 74 children out of 2,298 who took antidepressants engaged in a "suicide-related event," compared to 34 of the 1, 952 patients who took placebos, or fake pills. The drugs presenting the highest risk were Effexor and Paxil, which nearly tripled the risk of a suicidal event, and Zoloft, which more than doubled the risk, his research showed.

Prozac, which is now available in generic form, had the lowest risk among the major drugs, and is the only new-generation antidepressant specifically approved by the FDA for treating depressed children. For that reason, Mosholder recommended that Prozac alone continue to be prescribed to children.

But since drugs that have been cleared by the FDA for treatment of adults can be prescribed "off label" to children, other drugs including Paxil, Zoloft, Effexor, Luvox, Remeron, Celexa, Serzone and Wellbutrin are widely prescribed for children and teenagers. The FDA estimates that nearly 11 million antidepressant prescriptions were written for children in 2002, 2.7 million of them for children under 12.

Joseph Glenmullen, a clinical instructor in psychiatry at Harvard University, said the agency's withholding of the Mosholder report and its failure to take stronger action was an example of the FDA's failure to protect the public from the dangerous side effects of antidepressants.

"They have mishandled this issue for 15 years," he said. "They have not adequately protected American children."

FDA TO DRUGMAKERS: Suicide Warning Urged

Tue, 23 Mar 2004 00:00:00 -0800

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Federal regulators yesterday asked pharmaceutical companies to strengthen the wording on labels on 10 antidepressants to warn the drugs may heighten risk of suicide.

"We don't know yet if there is a link between antidepressant use and suicide," said Dr. Thomas Laughren, team leader of the Food and Drug Administration's psychopharmacology group. But yesterday's recommendation comes on the heels of an FDA advisory committee's recommendation last month to add the warning while the committee continues to investigate. Laughren said the warning is intended for all ages, not just children and teenagers.

"This is a good warning," said Dr. Harold Koplewicz, director of New York University's Child Study Center in Manhattan, and an expert on childhood depression. Koplewicz said 11 million prescriptions for antidepressants were written last year, most probably issued by primary care doctors.

"We have very effective medicines, but doctors need to know how to use them," Koplewicz said. Side effects, such as anxiety, generally occur in the first few months on the drugs. This period is a critical window for observing whether patients are improving on the prescribed drug and dosage.

Medicines for which the new warning is recommended are Prozac, Zoloft, Paxil, Luvox, Celexa, Lexapro, Wellbutrin, Effexor, Serzone and Remeron.

The only medicine tested and FDA- approved for teenage depression is Prozac. It and two other selective serotonin reuptake inhibitors, or SSRIs, Zoloft and Luvox, are approved for obsessive-compulsive disorder in young people.

But anecdotal reports of suicides among young people taking SSRIs have appeared in recent years, sparking a debate on the safety of these medicines. Last year, the drug regulatory agency in the United Kingdom banned Paxil for use in children. The FDA quickly put together an advisory committee to review the science.

Now, the FDA has asked psychiatrists specializing in teenage suicide to go case by case through 25 papers, clinical trials that represent more than 4,000 young people, some of whom were reported to have made some suicidal gesture during the studies.

Psychiatrists at Columbia University College of Physicians and Surgeons, as well as others nationwide, will re-evaluate each case. "While we are trying to figure this out, we are urging doctors to be more cautious," Laughren said.

Dr. David Fassler, a child psychiatrist at the University of Vermont, appreciates the new warning, but worries that the attention may frighten some parents and reduce the likelihood that they seek help for their children. "That would be a tragedy," said Fassler, who thinks medicine, in conjunction with some form of talk therapy, can be extremely helpful. "One of the biggest risks is not treating at all," he said.

The 10 Drugs

The Food and Drug Administration yestefday asked makers of these antidepressants to add labels urging that patients on the drugs be monitored for signs they are at risk of suicide.

Prozac (fluoxetine)

Zoloft (sertraline)

Paxil (paroxetine)

Luvox (fluvoxamine)

Celxa (citalopram)

Lexapro (escitalopram)

Wellbutrin (bupropion)

Effexor (venlafaxine)

Serzone (nefazodone)

Remeron (mirtazapine)

New Warning Urged On Antidepressants

Tue, 23 Mar 2004 00:00:00 -0800

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The Food and Drug Administration urged drugmakers yesterday to put new warning labels on popular antidepressant medications, including Paxil, Zoloft and Luvox, alerting doctors and consumers to watch for suicidal tendencies, hostility and agitation in patients taking the drugs.

The agency's action focuses on 10 antidepressant drugs in all and follows a warning by the British government last year advising physicians not to prescribe most widely used antidepressants to children. Last month, families of American adolescents who killed themselves while taking the medications implored the FDA to take comparable steps, and an expert advisory committee urged greater vigilance in the use of the medications in children with depression.

The agency said it does not know whether the medications which include several drugs known as selective serotonin reuptake inhibitors, or SSRIs are responsible for reported side effects such as inner restlessness, agitation and suicidal thoughts in some people. Officials said they are drawing greater attention to known cautionary information while a team of outside researchers completes a comprehensive analysis of the possible risks.

Patients taking the drugs who experience behavioral side effects should contact their physicians, said Russell Katz, director of neuropharmacological drug products at the FDA. If the symptoms are new or severe, he added, doctors should consider lowering the dose or stopping the drug.

Yesterday's move by the agency calls for warning-label changes for adults as well as children, and for patients who are depressed as well as those who use the drugs for unrelated problems.

"The advice applies across the board whether the drugs are used for any indication -- psychiatric or not," Katz said.

Critics of the medications called yesterday's move a victory and demanded that the FDA go further. Although Prozac is the only one of this class of drugs that has been specifically approved to treat depression in children, doctors are writing tens of thousands of prescriptions for many of the others, based on their clinical judgment that the drugs are safe and effective.

"Doctors are going to be on the line not to prescribe them as if they were pacifiers," said Vera Hassner Sharav, president of the Alliance for Human Research Protection, a patient advocacy group based in New York.

Many critics complain that a majority of studies of the drugs in children found that the medications did no better than dummy pills in treating depression, but that these studies have been hidden from doctors and the public. The companies say the studies are proprietary.

Sharav and other critics charge that the FDA and the American psychiatric establishment, which has broadly supported the efficacy of the drugs, have been unduly influenced by the pharmaceutical industry. Dozens of lawsuits against the medications have been filed around the country.

Many psychiatrists say the medications save lives and warn that discouraging patients from taking them could lead to greater numbers of suicides. They insist that suicidal tendencies or attempts among patients taking the drugs are the result of underlying disorders, not the medications.

Rates of suicide among adolescents have generally declined as antidepressant use has surged in recent years, said Thomas P. Laughren, FDA team leader for psychiatric drug products. While no one knows whether the two trends are linked, he said at a news conference yesterday, such data framed the context in which the FDA acted.

The drugs affected by yesterday's announcement are Prozac, Zoloft, Paxil, Luvox, Celexa, Lexapro, Wellbutrin, Effexor, Serzone and Remeron.

Suicide Caution Urged For Pills

Tue, 23 Mar 2004 00:00:00 -0800

Millions of Americans using antidepressants should be watched closely for suicidal tendencies and the popular medications should carry stronger warnings, the government told drug makers Monday.

The Food and Drug Administration's directive goes further than ever before in cautioning people about antidepressants, which some blame for an increased risk of suicide attempts.

The FDA stressed that such a link has not been proved, and doctors say the medications are helping millions cope with devastating depression. But the agency determined that it makes sense to add the warnings while it continues to examine the issue.

"We think this is good advice, whether the drugs increase the risk or not," said Dr. Robert Temple, the FDA's chief of medical policy. "There's a reason people are put on therapy their depression is worse or somebody's worried about it."

Because of that, it's impossible to say whether some people attempt suicide because of the medication or the underlying depression that caused them to take the drugs in the first place, he said.

"In either case, you really need to pay attention in the early days," Temple said.

An FDA advisory panel had suggested the change last month after an emotional hearing with testimony from the parents of children and teenagers who attempted suicide or took their own lives after starting antidepressants.

In accepting the recommendation, the FDA is asking for the added warnings on Prozac, Paxil, Zoloft, Effexor, Celexa, Lexapro, Luvox, Remeron, Serzone and Wellbutrin. Drug companies do not have to comply with the request but typically follow the FDA's suggestions, an agency spokeswoman said.

Many of the medications belong to a newer class of antidepressants called SSRIs or selective serotonin reuptake inhibitors credited with successfully treating depression in millions worldwide.

But concerns have been simmering about the use of the medications in young people, especially after a British study last year found a slight increase in suicide attempts among children taking antidepressants versus those taking sugar pills.

In this country, the FDA looked at 25 studies involving 4,000 children, but experts were unable to make a definitive assessment because different researchers used varying definitions for suicidal behavior.

For example, one researcher classified a child hitting herself on the head as a suicide attempt, while another considered it an accident when a child stabbed himself in the neck with a pencil. The FDA has asked a panel of experts to review the data again and reclassify each instance under uniform criteria. The agency hopes the work will be completed by this summer.

In the meantime, the expanded wordings on labels should advise health-care providers to "carefully monitor patients receiving antidepressants for possible worsening of depression or suicidality, especially at the beginning of therapy or when the dose either decreases or increases."

Some of the symptoms to watch for are anxiety, agitation, panic attacks and insomnia. Doctors who see these behaviors in patients should lower the dosage or stop the medication altogether, the FDA said.

While supportive of the additional labeling, some mental-health professionals said they fear it could scare people away from the medications and from seeking help at all.

"Depression is a deadly illness," said Cynthia Folcarelli, executive vice president of the National Mental Health Association in Virginia, a consumer-advocacy organization. "We have more suicides in this country every year than homicides, so it really is a serious problem. We want to make sure that a full range of treatment options are available to people."

The U.S. surgeon general estimates there are 30,000 suicides every year in the United States. According to researchers with Columbia University, 10 percent of all youth suffer from depression, and 1,883 children ages 10 to 19 years old killed themselves in 2001.

Some say one problem is that antidepressant medications increasingly are being prescribed by family physicians, pediatricians and other doctors who are not specialists in mental-health issues. They may not be as familiar with the potential side effects from psychiatric drugs as mental-health professionals.

"Antidepressants are not to be prescribed lightly," said Dr. Alan Keck, an Altamonte Springs psychologist. "If someone is depressed, they are naturally at higher risk for suicide. So anyone who does this kind of work is going to be looking for these symptoms anyway. That's common sense."

"Where you have problems is if someone is just getting medication," Keck said. "If that's the extent of the treatment, then you've been done a disservice. They should be getting some kind of psychotherapy, too."

Some psychiatrists also say the drugs are being unfairly connected to suicide attempts because the medications ease the lethargy that often accompanies depression.

After they start taking the drugs, people who were harboring suicide tendencies all along may suddenly find themselves with enough energy to act on them, said Dr. Segundo Imbert, an adult and child psychiatrist with Florida Hospital.

Imbert said he has been prescribing antidepressants for children for about 15 years and thinks the drugs can be beneficial.

Just as with any medication, he said, antidepressants could have side effects, but a conscientious physician will be watching for them.

"I do think they continue to be a safe group of medications," Imbert said. "The only thing we have to do is be a little more aware of how to use them so as not to harm patients in any way."

Caution Urged In Use of Drugs For Depression

Tue, 23 Mar 2004 00:00:00 -0800

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Millions of patients taking popular antidepressants need close watching for the warning signs of suicide or other serious mental health problems, especially when the powerful drugs are first started or their dosage is changed, federal health officials cautioned Monday.

The advisory from the Food and Drug Administration does not tell people to stop taking medications such as Prozac, Paxil, Wellbutrin and Zoloft. Nor does it say antidepressants can lead to suicide. Federal regulators are awaiting more research before reaching any conclusions on whether the drugs give rise to suicidal feelings or actions.

Instead, FDA officials urged patients, doctors and other caregivers to watch for any unusual reactions to the medications. Patients who show warning signs such as talking about suicide or abruptly withdrawing from activities and loved ones should get prompt medical help, even if they are already being treated for depression. Makers of the drugs are also being asked to step up suicide warnings on package labels.

The FDA warnings will affect millions of Americans of all ages. Newer types of antidepressants were the third most commonly prescribed class of drug in 2003, pulling in $10.9 billion for their makers. Their use is growing in adults and children alike.

The 10 medications covered by the warning include Prozac and its generic forms, Zoloft, Paxil, Luvox, Celexa, Lexapro, Wellbutrin, Effexor, Serzone and Remeron. They are most commonly prescribed for depression, but some may be used to treat other conditions such as panic or obsessive-compulsive disorders.

Almost 180 million prescriptions for antidepressants were handed out in 2001, according to drug research firm IMS Health. But popularity doesn't make a medicine risk-free.

The FDA's action comes as questions about a link between antidepressants and suicidal feelings have grown, particularly in children and teenagers. The FDA has been reviewing a growing body of research into antidepressants and pediatric suicide, and health officials in Great Britain last year declared some newer antidepressants to be unsuitable for young people.

Doctors said the FDA warning offers a good reminder that antidepressants are powerful and often unpredictable.

``I think the recommendation is very reasonable,'' said Dr. Glen Elliott, director of the children's division of Langley Porter Psychiatric Institute at the University of California-San Francisco. ``These are potent medications.''

Suicidal feelings often accompany the very depression that makes such drugs appealing. But the FDA urged doctors and patients to pay closer attention, regardless of possible cause. Signs of increased anxiety, hostility or other conditions should also be noted and reported to a physician.

Many people respond well to antidepressants. But some may not work in a particular person, or trigger a wide range of side effects.

``It's really a trial-and-error process,'' said Tom Rimel, who started taking antidepressants alongside other patients at a Silicon Valley care center for people shedding dependency on alcohol and drugs. ``Being around so many people taking the drugs, you could really see the range of side effects and how many of the drugs didn't work.''

Rimel, 47, was diagnosed with depression at the center run by Kaiser Permanente and started taking Paxil in December 2001. In addition to meetings and classes, he got regular checkups from doctors and case workers.

That kind of attention meant his use of antidepressants got careful monitoring, he said. Paxil worked well for him for about a year but after developing liver problems, Rimel switched antidepressants.

``You need to have follow-up with the doctor and be on top of your symptoms,'' Rimel said. ``If the drug is not working, you need to speak up.''

Doctors said the most intensive monitoring is needed when someone first starts the drugs or has the dosage or medication changed. Antidepressants often take two to four weeks to work fully.

Someone who has been immobilized by depression may start to have more energy as the drugs kick in. But they may also still have depressed or suicidal thoughts -- and suddenly more of an ability to act on them.

``Those are the dangerous times,'' Elliott said. ``Someone may actually find they have the energy to act on suicidal impulses. You can't stop monitoring patients.''

Patients who notice any unusual effects from the drugs or have questions about their use should not abruptly stop taking them, FDA officials stressed. Doing so can be dangerous, and patients should talk with their doctor.

``It's very good to be aware,'' said Dr. Tiffany Ho, medical director of the Santa Clara County Health Department. ``But people shouldn't be overly alarmed. These medications have helped millions of people.''

Effexor Suicide & Suicide Attempt Side Effects Lawyer

Tue, 23 Mar 2004 00:00:00 -0800

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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. On October 25, 2006 the FDA advised doctors to prescribe the popular antidepressant Effexor in the smallest possible amounts to decrease the risk of overdose. The FDA in conjunction with Wyeth, the manufacturer of Effexor had reports of overdoses occurring in some patients, mostly in combination with alcohol or other drugs, the agency said in a statement.

Wyeth said in a letter it sent to doctors and health care providers that the reported overdoses resulted in death or symptoms such as rapid heartbeat, coma, seizures, vomiting and vertigo. Additionally the letter did not reveal how many overdose cases had been reported. The letter urged doctors to report any adverse reactions to Effexor to the company or to the FDA.

The FDA approved Effexor (Generic: Venlafaxine), manufactured by Wyeth, on July 17, 2000. Effexor, which is still on the market, has been linked with suicide, suicidal ideation, suicidal behavior and suicide attempts. Effexor is a SNRI antidepressant (serotonin norepinephrine reuptake inhibitor) and is used to treat depression and associated anxiety symptoms.

On September 16, 2004, the FDA acknowledged that a small number of children and teenagers who use Effexor become suicidal or have suicidal thoughts. As a result, a scientific advisory committee voted 15-8 recommending 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.

In August 2003, Wyeth issued a warning to doctors about clinical trial evidence linking iEffexor to suicidal thoughts in young patients, and the company added that warning to the drug's label. In what is known as a "Dear Doctor" letter, Madison-based Wyeth told health professionals that clinical studies of the long-acting version, Effexor XR, found a higher incidence in children of "hostility and suicide-related adverse events, such as suicidal ideation and self-harm." No children in the tests committed suicide. "You should be alert to signs of suicidal ideation in children and adolescent patients prescribed Effexor or Effexor XR (and) reassess the benefit-risk balance," the Wyeth letter states.

The caution comes after U.S. and British regulators said no one under 18 should take GlaxoSmithKline's popular antidepressant Paxil because it could increase a child's risk of suicide attempts. Pediatric patients already taking Paxil were told to stop use gradually, under a doctor's supervision.

Effexor generated $2.1 billion in sales in 2004, making it Wyeth's biggest selling drug.

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