Off-Label Sales of SSRIs Leads To More Litigation

Off-label prescribing of prescription drugs overall is widespread in the US, but nowhere is it more prevalent than with the antidepressant drugs known as selective serotonin reuptake inhibitors. A study in the June 2005, Journal of Clinical Psychiatry, found that 75% of the prescriptions written for SSRIs were for treatments not approved by the FDA.

The study's lead author, Dr Hua Chen, an assistant professor at the University of Houston, said the findings reveal a significant gap in the US drug safety system and off-label prescribing regularly exposes consumers to drugs that are untested for their condition.

The FDA approves drugs for uses that have been tested and proven to be safe and effective. The term off-label means prescribing a drug for a use not approved or for a different patient population, such as children instead of adults, or at a different dose or duration than was determined by the FDA to have a favorable risk-benefit ratio.

While doctors may legally prescribe a drug for an off-label use, drug makers are barred from promoting a drug for unapproved uses, but it is a widely known that it occurs on a regular basis. For instance, SSRIs are still being prescribed off-label for a multitude of unapproved conditions to patient groups that includes children as young as toddlers, the elderly, and pregnant women.

Over the past 20 years, SSRIs have been prescribed off-label for everything from anxiety to pain, insomnia, shyness, menstrual discomfort, dementia, restless leg syndrome, and a host of other invented disorders sold to the public with the help of industry funded front groups and PR firms.

Possibly with the exception of Vioxx, in the end SSRIs will probably hold the title for not only the most side effects but also for the most lawsuits filed against SSRI makers due to their conduct of concealing studies that identified serous adverse events while at the same time overstating their efficacy, in the name of profits.

This class of drugs has now been found to be associated with suicidality, extreme violence and homicide, several life-threatening birth defects, abnormal uterine or gastrointestinal bleeding, a decrease in bone mineral density, fertility problems, sexual dysfunction, and a severe withdrawal syndrome.

In large part because the SSRI makers have been ripping off public health care programs by billing the government for the vast majority of off-label prescriptions, Federal and state law enforcement agencies are zeroing in on the drug companies and the doctors who are writing the off-label prescriptions as a result of kickbacks of some form or another.

The various illegal marketing schemes are taking their toll on public health care programs. According to the US Department of Health and Human Services, in 2005, Medicaid paid $41 billion for prescription drugs, well over 4 times the $8.9 billion spent in 1994.

Several Congressional Committees are currently investigating the off-label promotion of drugs by the pharmaceutical industry. While testifying at a US House Committee on Oversight and Government Reform on February 9, 2007, Lewis Morris, Chief Counsel at the Department of Health and Human Services’ Office of Inspector General, informed members of Congress about the adverse effects of prescribing drugs for unapproved uses.

"Off-label promotion," he said, "may lead physicians to prescribe a product for a non-approved use based on false, misleading, or erroneous information to the medical detriment of their patients."

"In addition," Mr Morris continued, "off-label promotion fundamentally circumvents the FDA drug approval process, on which Americans rely to evaluate the safety and efficacy of pharmaceutical products."

Mr Morris warned that physicians may be under the wrong impression that they can demand “kickbacks from drug companies with impunity,” because in the past prosecutors have focused on the drug makers paying the kickbacks.

But in cracking down on doctors, Mr Morris told the Committee that the OIG plans to use its authority to impose monetary penalties and the exclusion of doctors from public health care programs who are found to be accepting kickbacks.

Ronald Tenpas, associate deputy attorney general in the Department of Justice, testified about the harm caused by the corruption of doctors on the public as a whole. "By inducing physicians to prescribe for uses that have not been approved," he said, "either by promoting compromised “science” or offering financial incentives, manufacturers are subverting a healthcare system that necessarily relies on the objective medical judgment of practitioners, and their actions may also harm the public health."

"It is clear,” Mr Tenpas said, “from our experience that drug company violations of the law are causing government health-care programs to pay too much for prescription drugs.”

"We are not seeing isolated instances of misconduct,” he told the panel, “but repeated practices within the industry that have resulted in significant loses to federal health-care programs.”

The majority of lawsuits against drug companies alleging illegal marketing schemes aimed at public health care programs were filed under the provisions of the Federal False Claims Act, which allows persons who find evidence of fraud to bring suit on behalf of the government and collect a percentage of the amount recovered.

These whistleblower cases are first filed under seal until the DOJ investigates the charges and decides whether to intervene. Over the past six years, the government has recovered close to $4 billion in 16 cases involving Medicaid with Pfizer paying the highest penalty of $430 million for the off-label marketing of the epilepsy drug Neurontin.

The list of side effects associated with SSRIs that have surfaced over the past 2 decades continues to grow every year. But ironically, the drug companies have been so adept at keeping negative information about SSRIs hidden that most of the side effects only come to light as a result of litigation.

All SSRI makers have lawsuits pending involving a variety of adverse events. For example, in June 14, 2006, SEC filings, Lexapro and Celexa maker, Forest Laboratories says the company is a named defendant in approximately 25 active lawsuits, with most alleging that Lexapro or Celexa contributed to persons committing or attempting suicide.

In addition, Forest is under investigation by the US Attorney’s Office for the District of Massachusetts to determine whether Forest committed civil and criminal violations of the Anti-Kickback laws related to the off-label marketing of Celexa and Lexapro.

However, legal experts say drug companies view lawsuits as a minor problem and chock them up to the cost of doing business. For instance, what are 25 lawsuits to Forest, when Celexa and Lexapro, accounted for 68% of the company's sales last year. In fact, Lexapro revenues were 16% higher in the 4th quarter at $464,100,000, compared to $399,381,000 in the same quarter the year before.

Raymond Badyna has a Lexapro-induced suicide lawsuit pending in New Jersey filed on behalf of his deceased son, Ray Badyna's estate, by attorneys, Derek Braslow and Harris Pogust, of the Pogust & Braslow, LLC firm, in Conshohocken, Pennsylvania.

Ray’s suicide was totally unexpected. His friends and family members say there is no logical explanation for it other then the effect of Lexapro. On October 7, 2003, Ray received great news that for the second year in a row, his job performance for the year had qualified him to receive the, "Countrywide Circle of Excellence Award.”

And yet two days later at age 32, he committed suicide. "Had Ray or his physician known of the increased risk of suicide and suicidal ideation from Lexapro," the lawsuit states, "Ray would have never taken the drug."

Although Ray said nothing to his family that would indicate he planned to kill himself, after his death, it became known that Ray had expressed thoughts about harming himself to other people. In one conversation with a friend, Ray complained that Lexapro was making him "feel weird" and he "had very strange thoughts running through his mind."

Mr Braslow explains that SSRIs are designed to alter serotonin levels in the brain. "For years," he reports, "it has been known that serotonin functioning is directly related to aggression and violence, both directed at oneself and at others."

"Unfortunately," he states, "there is a vulnerable population of patients who are at an increased risk of violence and suicide as a result of taking Celexa, Lexapro and other SSRI drugs."

According to Attorney Pogust, the SSRI manufacturers have known about this population of high-risk patients for many years. "And, yet," he says, "these companies have failed to conduct any tests to determine the frequency of this phenomenon or to develop ways of identifying and protecting those patients who are in the high risk group."

As far back as November 1991, Dr John Mann, who now regularly serves as an expert witness for SSRI makers, coauthored an article titled, "The emergence of suicidal ideation and behavior during antidepressant pharmacotherapy," in the Archives of General Psychiatry in which he discussed the phenomenon of "iatrogenic suicide," also known as physician-induced suicide, and warned that there may be a "small vulnerable subpopulation" of patients for whom SSRIs pose a risk of suicide or violence.

In the paper, Dr Mann took it a step further and suggested protocols for studies that could be used to test this hypothesis and the drug companies deliberately did not conduct the research because they knew it would confirm Dr Mann‘s findings and a warning of such serious adverse events on the labels of SSRIs would have had a negative impact on sales.

"But worst of all," Mr Braslow says, "is that the SSRI manufacturers failed to warn prescribing physicians about the suicide risk or to instruct them on ways to reduce the risk."

Lexapro did not help Ray's condition and in 20/20 hindsight, his family recalls that after he began taking the drug, Ray immediately began to deteriorate. They maintain that had they been instructed to watch for signs of suicidality, Ray would still be alive.

Although it is largely unknown to the public, over the past 15 years, hundreds of SSRI-related lawsuits have been quietly settled out of court. The drug companies have gone to great lengths to avoid jury trials in order to keep the particulars of the lawsuits and the health risks associated with SSRIs hidden from public view.

However, in recent years, the filing of lawsuits has picked up speed as more people become aware of the link between SSRIs and serious side effects, usually as a result of media attention focused on information uncovered in litigation. More often than not, the information verifies that the drug companies intentionally concealed their own negative studies showing the health risks associated with SSRI and their lack of efficacy.

One FDA evaluation that surfaced as a result of litigation on the spontaneous post-marketing reports of "hostility" and "intentional injury" by people on Prozac, generated shortly before a 1991 FDA advisory committee meeting, compared SSRI suicidality to the antidepressant, trazodone, and found a 20-fold increase in reports of hostility and intentional injury in patients on Prozac.

The lawsuit filed on behalf of Ray Badyna, specifically cites an article published in 2000, on a study funded in part by Prozac maker Eli Lilly, and Paxil maker SmithKlineBeecham, that found the incident of deliberate self-harm by patients taking SSRIs to be 5.5 times higher than persons taking tricyclic antidepressants.

Recently a document became public that clearly shows the manipulation of study results in articles published on Pfizer’s Zoloft (sertraline), by the medical communications agency, Current Medical Directions in 1998.

The CMD published 6 articles on Zoloft use with children but all total, only 1 article mentions one suicidal act. However, according to Dr David Healy, one of the world's leading authorities on SSRIs, and author of "Let Them Eat Prozac," and "The Antidepressant Era," there were 6 suicidal acts.

He says, the rate of suicidality in children taking Zoloft was in fact 9%, but Pfizer got away with not publishing these negative findings by only reporting side effects that occurred at a rate of 10% or higher.

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

The kinds of suicides that experts say are SSRI-induced are extremely violent, totally unexpected and impulsive. Notes are seldom left and many suicide attempt survivors recall a strange out of body like experience.

For instance, 71-year-old Milton Cole, who was in good health and not depressed, went to a heart doctor with chest pains. After tests failed to reveal a heart problem, the doctor gave Mr Cole free samples of Prozac, supposedly to relieve the chest pain. Thirteen days later, his wife found him hanging from a beam in a back room of their shop, according to the November 3, 2003 Miami Herald.

Dr Joseph Glenmullen, author of "Prozac Backlash," and "The Antidepressant Solution," explains that the difference between ordinary suicidality and SSRI induced suicidality can be distinguished because an activation syndrome usually accompanies SSRI suicidality, which includes akathisia and mania.

Harvard trained psychiatrist, Dr Stefan Kruszewski, agrees and says, "Because the drugs cause predictable neurochemical changes in the central nervous system, SSRIs can also increase the risk of violence and aggressive acting out."

On March 22, 2004, the FDA issued an Advisory warning that symptoms such as akathisia, anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, hypomania, and mania had been reported in patients taking Prozac, Zoloft, Paxil, Luvox, Celexa, Lexapro, Wellbutrin, Effexor, Serzone and Remeron and recommended close observation of patients for worsening depression or emergence of suicidality.

According to Attorney Braslow, at the time of this warning it was revealed that Forest had added a suicide warning on Celexa sold in Europe years earlier, but in the US there was no such warning on Lexapro or Celexa.

"In addition," Mr Pogust reports, "the drug maker had previously conducted a number of European trials with both hospitalized and outpatient adolescents which showed Celexa to be no more effective than a placebo."

In May 2005, the FDA published the alarming suicide rate for children taking SSRIs in a Public Health Alert that stated “1 in 50" kids on SSRIs become suicidal or have increased suicidality “DUE TO DRUG.”

The next month, another FDA Advisory warned that adult patients "should be watched closely for worsening of depression and for increased suicidal thinking or behavior."

In addition to suicide, some of the most serious adverse events reported to be associated with SSRIs in recent years, are birth defects. Many studies have determined that SSRIs are harmful to the unborn fetus. In April 2006, a study in the American Journal of Obstetrics and Gynaecology, by Canadian researchers, found that SSRIs use during pregnancy doubled the mother’s risk of delivering a stillborn infant and increased the risk of premature delivery, underweight babies, and seizures.

These findings are important for doctors to know because according to a report by CDC researchers last year in Pediatrics, preterm birth is the leading cause of infant mortality in the US, accounting for at least a third of all deaths in 2002.

The harms to the fetus reported include a withdrawal syndrome, requiring prolonged hospital stays, respiratory support and tube feeding and a 6-fold increase in the life-threatening lung disorder, persistent pulmonary hypertension, as well as serious heart birth defects that require open heart surgery to correct.

In September 2005, studies conducted by Danish and US researchers found that the use of SSRIs in the first 3 months of pregnancy was linked to a 40% increased risk of birth defects such as cleft palate, and a 60% increase in cardiac defects. One study of 1,054 women who took SSRIs found they increased the risk of premature birth by 40%.

As a result of the rising number birth defects found to be associated with SSRIs, drug companies are facing a slew of lawsuits. They are reportedly especially worried about birth defect information becoming public because medical experts estimate that tens of thousands of infants in the US have SSRI-related birth defects, with the blame largely unknown to the parents.

Nearly 10 years ago, one of the harshest admonishments about the over-prescribing of SSRIs came in an Editorial in the October 20, 1997, issue of Time Magazine by Candace Pert, a professor at Georgetown University Medical Center at the time, as one of the two scientists who discovered the serotonin binding process, which stated in part:

I am alarmed at the monster that Johns Hopkins neuroscientist Solomon Snyder and I created when we discovered the simple binding assay for drug receptors 25 years ago.

Prozac and other antidepressant serotonin-receptor-active compounds may also cause cardiovascular problems in some susceptible people after long-term use, which has become common practice despite the lack of safety studies.

The public is being misinformed about the precision of these selective serotonin-uptake inhibitors when the medical profession oversimplifies their action in the brain and ignores the body as if it exists merely to carry the head around!

"In short," she warned, "these molecules of emotion regulate every aspect of our physiology."

Dr Healy says SSRIs continue to be over-prescribed even as researchers are finding more and more adverse events and doctors need to fully explain these side effects before prescribing the drugs so patients can make an informed choice about taking them.

Persons interested in more information on legal matters related to SSRIs can contact the Pogust & Braslow law firm at 610-941-4204, or http://www.pogustbraslow.com/

Evelyn Pringle

evelyn-pringle@sbcglobal.net

(Evelyn Pringle is a columnist for OpEd News and an investigative journalist focused on exposing corruption in government and corporate America)

(This article is part of a series covering litigation involving the pharmaceutical industry and is sponsored by the Pogust & Braslow, LLC law firm)

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