Weighing Benefits of SSRIs Against Suicide Risk

Evelyn Pringle December 8, 2006

Before the FDA’s Psychopharmacologic Drugs Advisory Committee begins the discussion at the December 13, 2006, public hearing on the suicide risks associated with selective serotonin inhibitor antidepressants, it should get honest with the audience and openly admit that the SSRIs do not even work.

Medical professionals maintain that in order to justify the use of a drug, its benefits are supposed to outweigh its risks and therefore, there should be a discussion of exactly what benefits result from the use of SSRIs, in any population, that would outweigh the suicide risks associated with this class of medications.

The most popular SSRIs sold in the US include Paxil, Prozac, Zoloft, Lexapro and Celexa.

As far as the benefits of the various SSRIs, an April 2002 study in the Journal of American Medical Association compared the effectiveness of Zoloft, St John’s Wort, and a placebo and found that the placebo treated patients had the highest rate of remission of symptoms at 31.9%, and Zoloft’s 24.8% was barely better than the rate of remission with St John’s Wort of 23.9%.

The FDA’s own records on Celexa (citalopram) show the agency knew the drug to be ineffective when it was approved, and the agency based its approval on 2 marginally positive studies out of a total of 17 conducted.

A March 26, 1998, memorandum by Thomas Laughren, of the FDA’s Psychiatric Drug Products, notes a total of 17 clinical trials on Celexa, including 2 uncontrolled trials, 6 active controlled trials showing no difference between treatments, and 2 placebo controlled trials that were too small to be considered studies.

Dr Laughren’s memo discusses 5 short-term trials (85A, 91206, 86141, 89303, and 89306) and 2 long-term studies (89304 and 89305). “In summary,” he wrote, “I consider studies 85A and 91206 positive support for the claim of short-term antidepressant efficacy for citalopram.”

“While 3 other placebo-controlled short-term trials (86141, 89303, and 89306) were negative, and not easily interpretable since there were no active control arms,” he stated, “I feel there were sufficient reasons to speculate about the negative outcomes and, therefore, not count these studies against citalopram.”

Dr Laughman also counted 2 relapse prevention trials as effective to support the drug’s approval. “Overall,” he wrote, “I consider these results sufficient to support claims of both short-term and long-term antidepressant effectiveness of citalopram.”

However, other FDA officials were not so eager to stretch the truth about the weak studies with medical professionals and consumers. For instance, a May 4, 1998 memo by Paul Leber, Director of the Division of Neuropharmacological Drug Projects, on the subject of “Approvable Action on Forrest Laboratories NDA 20-822 Celexa,” said the pubic had a right to know the truth about all the trials submitted to the FDA for the approval of Celexa.

He advised that the drug labeling should not only describe the trials that showed Celexa’s adequate effects; but should also describe the “well controlled clinical studies that failed to do so.”

Dr Leber specifically pointed out that Study 86141, Study 89303, and Study 89306, all failed to provide results confirming the positive findings of Studies 85 and 91206, the two clinical trials that Dr Laughman listed to support the approval of Celexa.

“I am aware that clinical studies often fail to document the efficacy of effective drugs,” Dr Leber wrote, “but I doubt the public, or even the majority of medical community, are aware of this fact,” he said.

“I believe that labeling,” he stated, “that selectively describes positive studies and excludes mention of negative ones can be viewed as being potentially “false and misleading.””

“I believe it is useful for the prescriber, patient, and 3rd party payer to know,” Dr Leber wrote, “without having to gain access to official FDA review documents, that citalopram’s antidepressants effects were not detected in every controlled clinical trial intended to demonstrate those effects.”

“I am persuaded,” he stated, “they not only have a right to know, but should know.”

When Forest Labs got Lexapro approved in 2002, it was nothing more than a chemically altered version of Celexa, and Forest Labs spent a fortune on persuading doctors to switch patients to Lexapro before its top selling drug Celexa lost its patent protection in 2004.

At the time, Forest could point to only one lone study, that the company itself paid to have published that claimed Lexapro was any better than Celexa. The paper, by Dr Jack Gorman, of the Mount Sinai School of Medicine, pooled the results of three studies and concluded that Lexapro “may have a faster onset” than Celexa, according to a report by Melody Peterson in the November 22, 2002 New York Times.

Dr Gorman’s paper was published in CNS Spectrums, a medical journal he edits, and Forest paid Medworks Media, a small medical marketing company that publishes the journal, to print the article in a special supplement.

Other researchers disagreed with the study results. “The Medical Letter, a nonprofit newsletter respected for its independence from the pharmaceutical industry,” Ms Petersen reports, “reviewed the same clinical trials as Dr. Gorman and concluded … that Lexapro had not been shown to be better than any other antidepressant, including Celexa.”

As for Paxil, in June 2004, New York State Attorney General, Eliot Spitzer, charged GlaxoSmithKline, with fraud for hiding studies that “not only failed to show any benefit for the drug in children but demonstrated that children taking Paxil were more likely to become suicidal than those taking a placebo.”

According to Mr Spitzer, Glaxo published only one of 5 studies it conducted, and even that one showed mixed results.

Prozac (fluoxetine) was also known to be ineffective before it was approved for use in the US. While serving as an expert witness in a lawsuit, psychiatrist and SSRI expert, Dr Peter Breggin, author of, “Talking Back to Prozac,” reviewed a July 1985 in-house analysis by its maker, Eli Lilly, that showed Prozac had failed to demonstrate efficacy in clinical trials with patients taking Prozac verses a placebo or a tricyclic antidepressant.

“When this potential economic disaster for Eli Lilly was discovered,” Dr Beggin reports, “the FDA allowed the company to include in its efficacy data those patients who had been illegally treated with concomitant benzodiazepine tranquilizers in order to calm their over stimulation.”

“Basically, Prozac was approved in combination with addictive benzodiazepines such as Ativan, Xanax, and Valium,” he says, “but neither the FDA nor the drug company revealed this information.”

“With these patients included,” he states, “statistical manipulations enabled the FDA to find the drug marginally approvable.”

An internal Lilly document dated March 29, 1985, says, “The benefits vs. risks considerations for fluoxetine currently does not fall clearly in favor of the benefits.”

Medwatch is the reporting system by which adverse events involving prescription drugs are reported to the FDA. Within one decade of Prozac’s arrival on the market, there were 39,000 adverse event reports submitted to Medwatch and that number is said to represent only about 1% of the actual number of adverse events, according to an April 22, 2006 report by the Citizens Commission on Human Rights.

Serious questions about the possible link between suicide and SSRIs began in 1990, when Martin Teicher, of McLean Hospital in Massachusetts, reported on 6 patients who he said experienced “intense, violent suicidal thoughts” after taking Prozac.

He offered three possible theories for the increased suicidality: (1) SSRIs gave patients more energy before lifting their depression, allowing them to act on a suicidal impulse; (2) the drugs worsened depression in a small subset of patients; or (3) SSRIs caused a state of agitation and restlessness.

In a February 10, 1990, report titled, “Emergence of Intense Suicidal Preoccupation During Fluoxetine Treatment,” Dr Teicher said, “The purpose of this report is to suggest the surprising possibility that fluoxetine may induce suicidal ideation in some patients.”

“In our experience,” he wrote, “this side effect has occurred in 3.5% of patients receiving fluoxetine.”

Throughout the 1990s, Eli Lilly publicly denied that Prozac was associated with suicide or violence, but by the year 2000, the company had quietly paid an estimated $50 million to settle over 30 lawsuits, according to an Indianapolis Star investigation.

When reviewing Lilly’s studies on Prozac, Dr Breggin found that there were 12 suicide attempts in the Prozac group verses only one in the placebo group and one in the tricyclic antidepressant group, but that many of the suicide attempts were hidden under false categories.

“Even after the company winnowed out six of the suicide attempts,” Dr Breggin says, “the remaining 6:1 ratio was alarming.”

He also reviewed a November 8, 1998, study titled, “Activation and Sedation in Fluoxetine Clinical Trials,” that showed a 38% rate of stimulation in the patients taking Prozac, even though, he says, many patients were sedated and many parameters of stimulation were not counted.

Another group of documents that he examined, contained a study conducted by the FDA on increased spontaneous post marketing reports of “hostility” and “intentional injury” by patients on Prozac. “These documents,” Dr Breggin says, “were generated shortly before the 1991 FDA PDAC meeting that evaluated antidepressant-induced suicidality.”

For this study, the FDA used the antidepressant, trazodone, as a control and found a 24-fold relative increase of reports of hostility and intentional injury per prescription of Prozac when compared to patients on trazodone.

“The spike in Prozac reports,” Dr Breggins says, “occurred even before any public controversy surrounding Prozac and violence.”

The documents he reviewed also contained graphs showing a 40-fold relative increase in reports of suicide attempts, overdose, and psychotic depression, in patients on Prozac compared to patients on trazodone.

“In one memo,” Dr Breggin reports, “a Lilly employee expresses shame and regret about hiding this data.”

In the case where Dr Breggin testified, Lilly was able to have the records sealed by the court where they remained hidden for roughly 10 years.

On April 10, 2004, the British Medical Journal, citing Jurendi et al, criticized the authors of studies on SSRIs for exaggerating benefits and downplaying their harm and noted a clinical trial of 93 children on Paxil that produced 11 serious adverse events, including 7 hospitalizations, compared to only two in children in the placebo group.

But the Paxil suicide risk does not only apply to children. An August 22, 2005, study by Norwegian researchers found that Paxil also increases suicide risk in adults. In the study of over 1,500 adults, 7 Paxil patients attempted suicide compared to only one attempt in the group of patients on a placebo. The researchers recommended that the warning not to prescribe Paxil to children should be extended to adults.

In Insight News, on October 4, 2002, investigative reporter, Kelly Patricia O’Meara, author of, “Psyched Out, How Psychiatry Sells Mental Illness and Pushes Pills That Kill (2006),” revealed a study conducted by Dr Arif Khan, medical director of the Northwest Clinical Research Center in Bellevue, Washington, that disclosed the number of suicides committed or attempted by patients in the clinical trials on SSRIs, that were kept hidden from doctors and consumers.

For the study, Dr Khan examined the official clinical drug-trial data for all SSRIs approved by the FDA between 1985 and 2000.

According to Ms O’Meara, the rate of suicides in the general public is 11 in 100,000, but the incidence rate for people participating in the SSRI trials was 718 for every 100,000. Dr Kahn’s research also revealed that nearly 4% of study participants attempted suicide within the following year.

As for weighing the benefits against the above risks, the British Medical Journal published a study on July 16, 2005, by Joanna Moncrieff, senior lecturer in psychiatry at University College London, that found SSRIs no more effective than a placebo in reducing depression.

The study also found that trials on SSRIs with negative results were less likely to be published than those with positive results, and that even in the published trials, negative outcomes were often not presented.

Dr Moncrieff said she found “no good evidence that these drugs work.”

Lexapro Legal Problems Mount Against Forest Laboratories

Evelyn Pringle November 15, 2006

According to Forest Laboratories’ Annual Report, for the year ending March 31, 2006, Celexa and Lexapro, accounted for 68% of the company’s sales.

The drugs belong to the class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs).

Sales of Lexapro, the filing notes, increased 16% in the 4th quarter to $464,100,000, compared to $399,381,000 in the same quarter a year ago.

However, the Report filed with the SEC on June 14, 2006, also says that Forest Labs is currently a named defendant in approximately 25 active SSRI related lawsuits, with most of the cases claiming that Celexa or Lexapro caused or contributed to persons committing or attempting suicide.

On November 7, 2005, Forest moved to consolidate all of the cases pending in Federal courts into a multidistrict proceeding, and on February 6, 2006, its motion was granted and multidistrict litigation was established with the cases then pending transferred to Judge Rodney Sippel in the US District Court for the Eastern District of Missouri.

But the company’s legal troubles by far are not limited to a few civil lawsuits. The US Attorney’s Office for the District of Massachusetts is investigating whether Forest has committed not only civil violations but also criminal violations of the Federal Anti-Kickback laws with “off-label” promotional activities in the marketing of Lexapro and other products.

As part of the investigation, Forest first received a subpoena from the Office of Inspector General of the Federal Office of Personnel Management requesting documents relating to Celexa, but the company has since received another subpoena from the US Attorney’s Office related to Lexapro and other products.

The subpoenas request documents relating to a broad range of the company’s marketing and promotional activities dating back to January 1, 1997, all the way up to the present.

The truth is, right along with all the other SSRI makers, Forest has been marketing Lexapro for the off-label treatment of a wide variety of ailments in part, by promoting the notion that every uncomfortable feeling is caused by a “chemical imbalance.” However, according to Dr David Healy, “none of the SSRI manufacturers can tell us what constitutes a proper chemical balance of serotonin in the brain.”

“Thus,” he says, “the truth is that Lexapro and its serotonergic cousins lie somewhere on the continuum between “magic bullets and snake oil.”

Dr Healy is one of the world’s leading authorities on SSRIs and the author of, “The Antidepressant Era,” and “The Creation of Psychopharmacology.”

To expand the market for SSRIs, the drug companies have transformed everyday sadness, stress, and worry into mental disorders that demand one cure: drugs. Strong emotions felt after the death of a loved one, or a divorce, or job loss are now irrational and symptoms of mental illness.

In fact, over the past 15 years Big Pharma has managed to cultivate the development of a whole new batch of mental illnesses, with names like generalized anxiety disorder, social anxiety disorder, panic disorder, and premenstrual dysphoric disorder, by simply greasing the palms of the so-called psychiatric “experts” who determine the criteria for the inclusion of a disorder in the Diagnostic and Statistical Manual for Mental Disorders (DSM).

Other more recent additions to the DSM, intended to further widen the customer recruitment net to specifically target children, have names like reading disorder, mathematics disorder, disorder of written expression, and oppositional defiant disorder.

And with the inclusion in the DSM, comes the guaranteed payment for the drugs to treat the disorder from public and private health insurance programs. The first edition of the DSM had a little over 100 disorders; the latest edition lists close to 375.

The mass marketing of mental illness has led many people experiencing minimal symptoms of distress to believe they need drugs to exist. And because most doctors are not trained on the side effects of SSRIs, patients can exhibit a wide range of actions or behaviors that appear to be symptoms of another “disorder,” and are then prescribed more drugs to counter the unrecognized adverse reactions to the first.

Even the medical education courses that doctors must take each year to maintain their professional license are most of the time sponsored by drug companies which means the courses are intended to increase the sale of specific drugs, and to educate doctors on their adverse effects would defeat the whole purpose of the seminar.

In fact, experts say the drug makers continue to ignore and discount all of the adverse effects associated with SSRIs. For instance, sexual dysfunction, such as lack of libido or interest, orgasmic dysfunction in women, and delayed ejaculation in men, are extremely common but seldom mentioned. Studies have shown that as high as 70% of patients on SSRIs experience sexual side effects.

According to WebMD, on July 2005, these side effects cause significant problems of their own. “For both men and women, this means being unable to initiate, participate fully in, or enjoy sex,” the article states, “and that can lead to a crippling loss of self-confidence that can, in turn, undermine depression recovery.”

But then not to worry, because a study in the January 1, 2003, Journal of the American Medical Association says that people experiencing SSRI related sexual dysfunction may be helped by simply taking another pill, Viagra.

And, although the FDA has not approved Viagra for women, some “experts” recommend that women experiencing SSRI related sexual problems should give it a shot anyways.

Whenever possible, patients are convinced that they need to take SSRIs for life. It would be interesting to see the results of a survey that asked patients if they would be willing to begin a life-long drug treatment if it meant waving good-by to a normal healthy sex life.

As a follow-up, a survey should also be conducted on the partners of SSRI patients to find out how long they will be willing to remain in what often becomes a sexless relationship.

The drug companies have also tried for years to discount the many studies showing an increased risk of suicide in patients taking SSRIs, when compared to patients taking a placebo, by claiming that suicide is a side effect of depression.

This claim is an insult to the intelligence of consumers. If that assertion were true, there would be more suicides by people taking placebos, not the other way around.

An FDA patient information sheet for Lexapro now says: “Persons taking Lexapro may be more likely to think about killing themselves or actually try to do so, especially when Lexapro is first started or the dose is changed.”

“People close to persons taking Lexapro can help by paying attention to changes in user’s moods or actions,” the paper says. “Contact your health-care professional right away,” it warns, “if someone using Lexapro talks about or shows signs of killing him or herself.”

“If you are taking Lexapro yourself and you start thinking about killing yourself,” it instructs patients, “tell your health-care professional about this side effect right away.”

That simple warning, critics say, added to the doctor and patent information sheet for SSRIs when the problem was first discovered could have saved tens of thousand of lives.

One of the Lexapro-induced suicide lawsuits mentioned in Forest’s Annual Report, was filed by Raymond Badyna, as the administer of his deceased son, Ray Badyna’s estate.

The action was filed in the US District Court for the District of New Jersey on September 25, 2005, by attorneys, Derek Braslow and Harris Pobust, of the Pogust & Braslow, LLC law firm in Conshohocken, Pennsylvania.

On September 30, 2003, Ray was prescribed Lexapro by his primary care physician who noted that Ray was experiencing anxiety, depression and was having problems relaxing and sleeping at night.

Ray’s doctor said that he prescribed Lexapro because he believed the drug was effective in treating depression and anxiety based on research that was distributed by Forest Labs.

However, the drug did not help and Ray’s condition immediately began to deteriorate. Friends and co-workers spoke with Ray concerning his use of Lexapro and they recall that Ray said that he was not feeling himself and feeling very strange.

At his sister’s birthday party on October 4, 2003, the family observed Ray as appearing extremely withdrawn, tired and isolated. His sister noticed that he was pacing back and forth throughout the house, looked uneasy, and that his hands were shaking.

His sister became convinced that something was seriously wrong with Ray and she was right. Unbeknownst to his family, Ray was suffering from suicidal ideation and had expressed thoughts about harming himself to others.

In a conversation with his friend, Ray complained that Lexapro was making him “feel weird” and said that he “had very strange thoughts running through his mind.”

On October 7, 2003, while at work, Ray got what should have been great news when he was notified that his year to date performance had qualified him to receive the, “Countrywide Circle of Excellence Award,” for the second consecutive year in a row.

Two days later, on October 9, 2003, Ray, age 32, committed suicide by overdosing and cutting his wrists. An autopsy showed the presence of Lexapro in his bloodstream.

Ray’s death was senseless. He life was a model for the all-American success story. He was popular, outgoing and sociable and had a loving close relationship with his family.

Ray had a college education, and a good career in real estate and owned his own home, as well as four other investment properties, and even a boat.

Family members, friends and co-workers alike, all say Ray was outgoing, had a great sense of humor, enjoyed life and seemed to everything to live for, prior to being prescribed Lexapro. If Ray’s family members had been told to watch for the warning signs that Ray was exhibiting, they would have intervened, and he would be alive today.

The family’s lawsuit alleges that in “the last decade there has been a host of peer-reviewed scientific literature linking the SSRI drugs, of which Lexapro is one, to violence – both self-directed and directed towards others.”

Among others, the complaint specifically cites a peer reviewed article published in 2000, on an epidemiological study, funded in part by Eli Lilly and SmithKlineBeecham, that reports that the incident of deliberate self-harm of people on SSRI medications is 5.5 times higher than that of people on the more traditional tricyclic antidepressants.

“Had Ray or his physician known of the increased risk of suicide and suicidal ideation from Lexapro,” the family’s lawsuit states, “Ray would have never taken the drug.”

Next year’s annual report will have new additions to the list of lawsuits against Forest. For instance, in July 2006, Mark Bibbee, filed a lawsuit after losing his only 2 sons to Lexapro-induced suicides. The family’s attorney, Charles E Grisi, filed the action in Summit County Ohio Common Pleas Court.

David Bibbee was only 27 when he killed himself on February 23, 2003 at his fathers home, and Brian Bibbee was only 24, when he committed suicide 17 months later at his mother’s home on July 24, 2004.

The lawsuit charges that Forest Labs knew of the increased risk of suicide, yet failed to conduct tests to see how often the problem occurred and failed to properly warn doctors, pharmacists and patients of the risk, or provide ways to reduce the risk.

The lawsuit points out that a link between SSRIs and suicide was first noted in 1990, even though the FDA did not issue a public health advisory until March 2004, more than a year after David’s death and about four months prior to Brian’s death.

“Strong warnings and instructions, coupled with reasonable effort to ‘get the word out’ could still have saved Brian Bibbee’s life,” the lawsuit states.

“Unfortunately,” the complaint charges, “Forest took the path of least resistance and greatest profits by doing only the minimum amount that the FDA urged it to do.”

“Therefore,” the lawsuits states, “this warning was ‘too little, too late’ for David and Brian Bibbee.”

These three cases of unexpected suicides by young people taking Lexapro are not isolated incidents. Jo Ann Kelly has been trying to raise awareness about the increased risk of suicide associated with SSRIs since her son, David died of a self inflicted gun shot wound after he was prescribed Lexapro for an anxiety disorder.

A few days before his death, Jo Ann noticed a dryness of skin and an increased agitation in David, and her son-in-law noticed a yellowish appearance in David’s eyes.

Jo Ann became frantic and feared that her son might not be metabolizing the Lexapro correctly so she called to schedule a doctor’s appointment but could not get in for 2 days.

The day of the appointment came too late; David had already shot himself.

Over the past several years, studies have shown that SSRIs are associated with serious birth defects in babies born to women who use the drugs during pregnancy. Within the last year, the FDA has added warnings to the labels on SSRIs about the risks of heart birth defects and a life-threatening lung disorder.

As a result of the new revelations about birth defects, lawsuits are now being filed against the SSRI makers on behalf of injured infants.

Medical professionals say the value of any drug must be determined by weighing its benefits against its risks. In the case of SSRIs, the benefits, if any, are a topic of great controversy. An analysis of studies submitted to the FDA between 1987 and 1999, on the six most popular SSRIs, found that approximately 80% of the positive responses to the drugs were the same in patients participating in the placebo groups.

Simply put, with all the known harms identified over the past 20 years associated with SSRIs, they do not even work.

More Adverse Effects Linked to SSRI Celexa

Evelyn Pringle November 14, 2006

According to testimony at an inquest into the deaths of Roxanne Richardson, 30, and her children, Luke, 3, and Grace, 20 months, an autopsy revealed that at the time of their murders, husband and father-turned-killer, Michael Richardson, had Celexa in his system higher than prescribed which may have caused him to become agitated and irritable.

When he arrived at the Richardson home on July 12, 2004, Detective Sergeant Fox said the four bodies lay side by side on a bed. The medical evidence was that Mrs Richardson had been stabbed in the chest and then suffocated, the children had been suffocated, and Mr Richardson had died from a gunshot wound, according to the November 1, 2006 Sidney Morning Herald.

A far cry from alleviating his depression, on the day of the tragedy, while pumped full of Celexa, Mr Richardson wrote in his diary: “I’m hurting so much, nothing matters to me any more except my family and they are getting taken away from me.”

Over the past 15 years, there have been a growing number of criminal cases where people have claimed that their aggression and violence was caused by the use of antidepressants like Celexa, a class of drugs known as selective serotonin reuptake inhibitors (SSRIs).

Psychiatrist, Dr Peter Breggin, author of 20 books including, “Toxic Psychiatry,” has been researching psychiatric drugs and serving as an expert witness and consultant in civil and criminal cases involving drug companies for more than 25 years.

In 1972, he founded The International Center for the Study of Psychiatry and Psychology (ICSPP), a non-profit research and educational network, focused on the impact of mental health theory and practices upon patient well-being, personal freedom, and family and community values. He also founded the journal, Ethical Human Sciences and Services.

According to Dr Breggin, all SSRIs can produce stimulation or activation with the potential for increased agitation, disinhibition, irritability, aggression, hostility, mania, and crashing into depression and suicide.

“They can also cause a flattening of emotional responses,” he notes, “including a loss of caring, that can unleash dangerous actions.”

“Beginning with the widespread use of Prozac in the early 1990s,” he says, “the struggle to gain public and professional recognition of antidepressant-induced suicide and violence has a long and stormy history. “

The debate peaked in 1994 when Dr Breggin testified against Eli Lilly in a case of Prozac-induced suicide and mass murder by a postal worker in Kentucky.

“My testimony, in effect,” Dr Beggin recalls, “was that the perpetrator, Joseph Wesbecker, hadn’t gone “postal,” he’d gone “Prozacal.”

After the drug company won a split jury decision at the end of the trial, the judge figured out that the trial had been fixed. “The plaintiffs,” Dr Breggin says, “had been paid off by the drug company to conduct a fake trial that was rigged to end in favor of the drug company.”

In the end, when the judge realized what happened, he was outraged and voided the verdict.

According to Dr Breggin, while the FDA and antidepressant makers continue to deny that SSRIs cause violence, many lives continue to come to tragic ends.

It wasn’t until late 2004, that the FDA finally made drug companies add a black box warning to the labels of SSRIs about the increased risk of suicide among patients taking the drugs, even though Dr John Abramson MD, author of, “Overdosed America,” and a clinical instructor at Harvard Medical School, says the FDA knew about the increased suicide risk since before the drugs were approved.

The findings from a study published in the Archives of General Psychiatry in 2000, he says, evaluating the findings from the “pivotal studies” submitted to the FDA on the 7 new antidepressants approved between 1987 and 1997, including Prozac, Zoloft, Paxil, Effexor, Serzone, Remeron, and Wellbutrin SR, went largely ignored.

In studies that included depressed but not suicidal patients, the completed suicide rate for those taking one of the new antidepressants was 842 in 100,000 per year, or 0.84%, while the rate of suicide for patients taking a placebo was less than half at 360 in 100,000, or 0.36%.

“In other words,” Dr Abramson explains, “the pre-approval studies considered by the FDA to be highest quality and most important for these 7 new and supposedly safer and more effective antidepressants showed that treating 1000 depressed non-suicidal patients for one year with the new drugs led to about 5 more successful suicides than if the same group of 1000 patients had been treated with a sugar pill.”

“This is an enormously high death rate,” he points out.

And although the incidence of violent behavior is not included in the above report on antidepressants, Dr Abramson says, “it certainly seems logical that when the risk of violent actions against self are more than doubled, that the incidence of violent actions against others might be similarly affected.”

At the very least, he notes, this possibility should have been studied.

Critics say, getting the FDA to issue warnings about the increased suicide risk with SSRIs was like pulling teeth. According to investigative journalist and author of, “Psyched Out: How Psychiatry Sells Mental Illness and Pushes Pills That Kill,” Kelly Patricia O’Meara, “based on the evidence that twice as many children in clinical trials showed a greater risk of suicidality taking the antidepressants, coupled with the evidence that the antidepressants in the majority of the clinical trials were no more effective than sugar pills, the FDA had little choice but to “request” the pharmaceutical companies add the black-box warnings.”

Also in 2004, what would become a steady stream of studies showing harm to infants born to mothers taking SSRIs began to emerge.

In February 2004, the study, “Maternal Selective Serotonin Reuptake Inhibitor,” by Philip Zeskind PhD and Laura Stephens, in the journal Pediatrics, reported that “first-trimester use of SSRIs has been associated with higher rates minor physical anomalies and miscarriages, thus suggesting possible early effects of SSRI exposure on embryonic development.”

The study also reported that third-trimester use off SSRIs had been associated with lower gestational age, low birth weight, higher rates of neonatal intensive care unit admissions.

In June 2004, a French study published in the journal Prescrire International, reported that newborns exposed to SSRI during pregnancy showed signs of agitation, altered muscle tone, and breathing and suction problems.

The following month, in July 2004, the FDA changed the labeling for all SSRIs, warning that some newborns exposed to SSRIs had developed problems requiring respiratory support, tube feeding and prolonged hospitalizations.

But as it turns out, the FDA had received hundreds of reports of adverse effects in infants born to mothers taking SSRIs over the past decade, according to WebMd. The most common adverse events reported included irritability, trouble eating, body rigidity, and respiratory problems, said Kathleen Phelan, a safety evaluator in the division of drug risk evaluation, to WebMD.

A February 2005 study in the journal, Lancet, screened the World Health Organization’s database on SSRI adverse reactions in cases of neonatal convulsions and withdrawal syndrome, and found that by November 2003, there was a total of 93 case reports of maternal SSRI use in babies born with convulsions or withdrawal syndrome.

An analysis of the reports showed 64 cases were associated with Paxil, 14 with Prozac, 9 with Zoloft, and 7 were associated with Celexa.

Research released earlier this year linked SSRI use by mothers during pregnancy to infants born with the life-threatening persistent pulmonary hypertension (PPHN) lung disorder. According to a study by researchers at the University of California, San Diego School of Medicine, in collaboration with Boston University’s Slone Epidemiology Center, in the February 9, 2006 New England Journal of Medicine, babies born to women who took SSRIs in the second half of pregnancy, had a 6 times greater risk of developing the lung disorder.

In September 2005, studies conducted by Danish and US researcher determined that SSRI use in the first trimester of pregnancy was linked to a 40% increased risk of birth defects such as cleft palate and that cardiac defects in newborns also appeared to be 60% more likely with women who used SSRIs.

In February 2006, a study conducted in Israel found that one out of 3 infants exposed to SSRIs in the womb showed signs of drug withdrawal at birth, including high-pitched crying, tremors, and a disturbed sleep pattern.

On April 7, 2006, the BBC reported a Canadian study of almost 5,000 pregnant women that found mothers on SSRIs were twice as likely to have a premature birth and also nearly twice as likely to have low birth weight infants and stillbirths.

Less than 3 months later, in July 2006, the FDA issued an advisory that warned against taking SSRIs together with triptans, drugs used to treat migraine headaches, because a life-threatening condition called serotonin syndrome may occur. The condition, the FDA said, causes serious changes in how the brain, muscles and digestive system work due to high levels of serotonin in the body.

Last month, doctors at the Cornell Medical Center, in New York, who were treating the two men for infertility, including one who was on Celexa, found that when the men stopped taking the SSRIs, their fertility problems disappeared, only to resume again when they went back on SSRIs.

The problem is believed to be caused by an adverse effect of SSRIs on both the concentration and swimming ability of sperm. The men were tested over a 2-year period

Dr Peter Schlegel, who presented the research at the American Society for Reproductive Medicine conference, in New Orleans, explained that:

“The patients had normal sperm counts and motility before medication. On the medication they have severe deterioration of both. The same patients going on and off medication had the same pattern. It shows a strong association.”

Impotence and delayed ejaculation are well-known side-effects of SSRIs, and now Dr Schlegel says he believes that the drugs may be preventing sperm from getting into semen.

“These were men with normal sperm counts that went to nearly zero when they were on these antidepressants but returned to normal when they were off them. It’s a dramatic effect and it’s never been described before,” said Professor Schelgel in the Guardian on October 24, 2006.

“We believe that while it’s had a profound effect on these two men,” he said, “it could be having a significant but more subtle effect on many more men.”

But no matter how many adverse events are found to be associated with SSRIs, there seems to be no way to curtail the over-selling of these drugs to all populations. For the year ending March 31, 2006, Forest Laboratories top selling drugs were the SSRIs, Celexa and Lexapro, which when combined, accounted for 68% of the drug maker’s sales.

However, there may be a few dents in the company’s profit margin for SSRIs in the coming years because according to Forest Lab’s Annual Report filed with the SEC on June 14, 2006, the company is a named defendant in approximately 25 active product liability lawsuits, with most alleging that Celexa or Lexapro caused or contributed to persons committing or attempting suicide.

In addition, Forest Labs may not know it yet, but the company will soon be hit with the first Celexa-related birth defect lawsuit alleging that the company engaged in “repeated and persistent fraud” by misrepresenting, concealing and otherwise failing to disclose, information concerning the safety and effectiveness of Celexa in treating pregnant women.

Named plaintiffs in the case will be Lacee Shore, who was prescribed Celexa during her first trimester of pregnancy and her baby Gavin Shore, who was born with heart birth defects. Attorney, Robert Kwok, of the Houston, Texas lawfirm Robert Kwok & Associates, LLP, is handling the case.

To cover lawsuits, according to Forest’s Annual Report, the company maintains $140 million of product liability insurance coverage per “occurrence” and in the aggregate.

However, in conclusion the Report points out that, “litigation is subject to many factors which are difficult to predict and there can be no assurance that we will not incur material costs in the resolution of these matters.”