Let's Get Honest! Absolutely Uncommon Analysis of Family & Conciliation Courts' Operations, Practices, & History

Washington, DC:

Eli Lilly, Johnson & Johnson, and AstraZeneca, are all named defendants in a new lawsuit filed by the state of Pennsylvania on February 26, 2007, to recover money paid through public health care programs to purchase Zyprexa, Risperdal, and Seroquel, and the costs of medical care for the people injured by these drugs.

Pennsylvania is the 5th state to sue Lilly over its illegal marketing of Zyprexa. And according to SEC filings, Lilly was served with four Canadian lawsuits in 2005, with claims “similar to those in the litigation pending in the United States.”

So far, two states have sued Johnson & Johnson over Risperdal, but Pennsylvania is the first state to file a lawsuit against Seroquel-maker AstraZeneca.

The drugs belong to a class known as “atypical” antipsychotics, FDA approved only to treat adults with schizophrenia or bipolar disorder, and yet they are some of the most widely prescribed drugs in the world. In 2006, Zyprexa sales were $4.3 billion, Seroquel’s earned $3.4 billion, and Risperdal had sales of $4.1 billion, according to SEC filings.

A July 2006, report by Decision Resources, a leading advisory firm on healthcare issues, listed antipsychotics in 2005, as the fourth-highest-ranking class of drugs, and said two of the top ten drugs in worldwide sales were atypicals.

According to the lawsuit, the defendant drug makers concealed the risks of atypicals and exaggerated their benefits while persuading doctors to prescribe the drugs off-label for dementia, attention deficit disorders, and mood and behavior disorders.

When the FDA approves a drug it also approves the label, which lists the indications for which the drug can be prescribed, along with instructions for use and warnings about the risks associated with the drug. Once a drug is approved to treat one condition, doctors may prescribe it for others if they think it will be effective, but by law drug companies are not allowed to influence physicians to prescribe a drug for indications other than those listed on the label.

On March 1, 2007, four days after the Pennsylvania lawsuit was filed, two of the three drug companies became the target of another investigation, when Representative, Henry Waxman (D-Cal), the chairman of the House Oversight and Government Reform Committee, sent letters to Eli Lilly and AstraZeneca, requesting information related to the exact same charges alleged in lawsuits filed by individual states.

The letter sent to Lilly states in part, “Allegations have been raised that Eli Lilly misled physicians and inappropriately promoted off-label uses of Zyprexa,” and requests information relevant to these allegations.

The letter asks for a list of all Zyprexa trials, studies, or reports; all presentations given to employees who promoted Zyprexa; information shown to physicians; presentations related to physician prescribing patterns, continuing medical education, and off-label use; and all documents and correspondence related to funding for nonprofit professional organizations or consumer patient groups.

In addition, Rep Waxman wants Lilly to turn over all internal company documents that were kept under seal for years with a court order, but were provided to him by Attorney, James Gottstein, in December 2006, which Rep Waxman subsequently returned to Lilly on December 21, 2006, to honor the court order.

According to the New York Times, some of these documents reveal that Lilly knew about Zyprexa’s link to high blood sugar and extreme weight gain that often leads to diabetes, and others show the details of off-label marketing scheme called “Viva Zyprexa.”

Rep Waxman’s letter to AstraZeneca basically asks for the same documents requested from Lilly except that he requests more information related to the physicians and authors involved in company sponsored studies and writing the reports.

Late last year, the atypical makers also received subpoenas from the attorney general of California seeking much of the same information.

 

In pursuing the Pennsylvania lawsuit, Governor Edward Rendell, has hired private attorneys. According to the complaint, the defendants cost Pennsylvania millions of dollars “for non-medically accepted indications and non-medically necessary uses of Zyprexa, Seroquel and Risperdal,” as well as “significant sums of money for the care and treatment” of patients injured by the drugs.

{{See also comments near bottom of article, I think, stating that Rendell already knew about these things, but was concerned about political status when it was outed.}}

The Pennsylvania case comes on the heels of lawsuits by two Pennsylvania whistleblowers, Allen Jones and Stefan Kruszewski, who say, drug companies are making a fortune from the off-label sale of drugs to patients whose care is funded by Medicaid and Medicare.

{{OK below here in this pink-background box, it’s all quote unless enclosed in my brackets, regardless of indent level….}}

At the heart of the off-label scheme, they say, are the preferred drug lists, or medication formularies, maintained in many states. Once drugs are added to the list, they must be prescribed as a first line of treatment for all patients in state run institutions and patients in the general population who are covered by public health care programs.
In the summer of 2002, psychiatrist, Dr Kruszewski, was employed with the Pennsylvania Department of Public Welfare, {{“DPW”}} and charged with reviewing psychiatric care provided by state-funded agencies to identify waste, fraud, and abuse. He was also responsible for reviewing the deaths of individuals in state care who died under suspicious circumstances in facilities inside and outside of Pennsylvania.

Early in his investigation, Dr Kruszewski noticed that almost all of the patients under state care were on drug cocktails consisting of antipsychotics, antidepressants, and anticonvulsants. The populations he found drugged most often, he said, were children in state care, the disabled, people in state prisons, and children in the juvenile justice system.

For instance, he says, Neurontin was only approved for controlling seizures, but “was being prescribed for anxiety, social phobia, PTSD, oppositional defiant behavior, and attention deficit disorder {{“ADD”}} with no evidence to support these uses.”

When he informed his superiors about the high rate of off-label prescribing and warned about the risk of liability to the state of Pennsylvania if it continued, he was told, “it is none of your business.”

In June 2003, Dr Kruszewski inspected a facility in Oklahoma that housed children from Pennsylvania after an unexpected death of a child, and found children were being overmedicated and housed in deplorable living conditions, in addition to being sexually and physically abused by staff and kept in unnecessary restraints and seclusion.

In a report, Dr Kruszewski recommended removing the children from the facility, “in order to protect other innocent individuals from morbid and mortal consequences of severe over-medication, including chemical restraints; emotional, physical and sexual abuse; seclusion; and dirty and inadequate living conditions.”

A day later, Dr Kruszewski was accused of “trying to dig up dirt,” and was subsequently fired in July 2004, because he refused to keep quiet and accept that it was none of his business, he says.

A year later, Dr Kruszewski filed a whistleblower lawsuit alleging that patients under state care were being drugged for profit and prescribed as many as 5 psychiatric drugs at the same time, and that four children and one adult had died.

In his action, Dr Kruszewski alleged that his superiors violated his right to free speech by firing him because he made statements about the abuses in the state system, which were a matter of public concern.

Dr Kruszewski is represented by attorneys from Government Accountability Project, Thad Guyer, Stephania Ayers, Tom Devine, and Mark Cohen, in Federal Court in the Middle District of Pennsylvania with Chief Judge Yvette Kane presiding.

Defendant, Christopher Gorton, is the Chief Medical Officer for DPW, who fired Dr Kruszewski. He filed a motion for summary judgment to dismiss the First Amendment claim on the basis that the law does not protect whistleblowers if they are fired for making comments they would be expected to make in the context of their employment.

{{To repeat:  An underling reports some horrific abuses of vulnerable populations and is fired by the “CMO of the DPW, who then tries to get the whistleblower lawsuit dismissed on WHAT irrational basis?}}

In reading the Court’s March 2, 2007, Decision denying Mr Gorton’s motion, it appears that Mr Gorton tried to have it both ways. When Dr Kruszewski was employed and tried to report the harm to people under state care, he was told it was none of his business and to quit digging up dirt. Under oath in a deposition, Dr Kruszewski stated that he was told that the subjects of his statements were not part of his job duties.

However, in his motion, Mr Gorton now claims that Dr Kruszewski’s comments were made pursuant to his official employment duties. In her written opinion, Judge Kane, quoted relevant case law to describe comments that are protected:

“A public employee’s statement is protected activity when (1) in making it, the employee spoke as a citizen, (2) the statement involved a matter of public concern, and (3) the government employer did not have an adequate justification for treating the employee different from any other member of the general public as a result of the statement he made.”

“The statements in question can be categorized,” Judge Kane wrote, “as: (1) reports regarding poor quality of care, including abuse of patients by staff at treatment facilities; (2) complaints about the lack of qualifications of another private contract doctor; and (3) statements about use and costs of medications.”

In order to grant a motion for summary judgment, a judge has to find that there are no genuine disputes of material fact that would require a jury to resolve. In this case, Judge Kane found there were disputes regarding Dr Kruszewski’s job duties and whether his statements were substantial and motivating factors in his termination.

In his motion, Mr Gorton claims the statements were not protected speech, but then says, even if they were, they were not a factor in his decision to terminate Dr Kruszewski, because he was unaware of the statements when he decided to fire Dr Kruszewski.

However, Judge Kane found evidence in the record that, “if credited by a fact-finder,” she wrote, “would support Plaintiff’s claim that Gorton knew of at least some of Plaintiff’s protected statements.”

“Because there remain genuine disputes of material fact,” she states, “regarding Plaintiff’s job duties and whether Plaintiff’s statements were substantial and motivating factors in his termination, the Court cannot grant summary judgment for Defendant Gorton.”

According to Dr Kruszewski, apart from all the legal wrangling, his focus remains on trying to protect Pennsylvania citizens against unwarranted drugging, sexual and physical abuse, and unnecessary restraint and seclusion.

His original lawsuit alleges that drug companies used “political friendships, money, and other emoluments” to achieve “a level of influence with Pennsylvania’s state government” to promote “the use of their products.”

These charges echo those previously made by the other Pennsylvania whistleblower, Allen Jones, who was also a fraud investigator in the Pennsylvania Office of Inspector General, Bureau of Special Investigations, and was fired after he informed his superiors that drug companies were funneling money to state officials and policy makers in positions of influence over the state’s preferred drug formulary known as PennMap.

Last year, Mr Jones settled a whistleblower lawsuit in Pennsylvania, also with the assistance of the Government Accountability Project. While he did not agree to a gag order regarding his concerns, he did agree not to discuss the terms of the settlement.

During his investigation, Mr Jones found collusion between drug companies and several state officials and specifically, Steven Fiorello, Pennsylvania’s chief pharmacist, a valuable player because he monitored pharmacy operations at 9 state hospitals and served on the committee that determined which drugs would be prescribed to patients in state hospitals.

On November 21, 2006, Mr Fiorello was arraigned on two felony counts of conflict of interest and misdemeanor counts of accepting money and failing to disclose the income on his yearly financial interest statements.

A year and a half earlier, the Pennsylvania State Ethics Commission had determined that Mr Fiorello had repeatedly violated state ethic laws by using his position to earn money from drug companies. To settle the charges with the Ethics Commission, Mr Fiorello paid fines totaling $27,269, before the case was referred for criminal prosecution.

Down in Texas, another state official, Dr Steven Shon was fired from his job in October 2006, after the state’s attorney general, Greg Abbot, found J&J had improperly influenced Dr Shon to list Risperdal in a state formulary called the “Texas Medication Algorithm Project,” or TMAP, while receiving money from J&J.

In December 2006, Mr Abbott joined another whistleblower lawsuit filed by Mr Jones, against J&J, alleging in part, that the company misrepresented the safety and effectiveness of Risperdal and unduly influenced Dr Shon and others, to make it a drug of choice for persons covered by public health care programs in Texas.

TMAP required doctors to prescribe atypicals rather than the older, less expensive antipsychotics. “c.

The lawsuit says, J&J promoted Risperdal by influencing policymakers with trips, perks, travel expenses, speaking fees and other payments and that Risperdal was recommended as the drug of choice for children, even though it was not approved for use with children.

TMAP was highly successful in getting doctors to prescribe atypicals to kids. According to an investigation of psychiatric drug use by Texas children on Medicaid, ACS-Heritage, a medical consulting firm, found 19,404 teens were prescribed an antipsychotic in July or August of 2004, with nearly 98% being atypicals.

ACS also found that more than half of the doses were inappropriately high, almost half of the prescriptions did not appear to have diagnoses warranting their use, and one-third of the children were on two or more drugs.

The Texas lawsuit alleges that J&J concealed Risperdal’s link to hyperglycemia, stroke, and renal failure, to qualify for reimbursement under Medicaid, and that Texas seeks to recover money paid to purchase the drug for off-label uses and the cost of medical care for the people injured by Risperdal.

In 2005 alone, according to the Texas Health and Human Services Commission, Texas paid for approximately 308,000 Risperdal prescriptions at a cost of $73.5 million.

Critics say, the Governor of Pennsylvania is suing atypicals makers now to portray a hard stance against the pharmaceutical industry because he wants to run for higher office, when in reality, he has known about the PennMap off-label scheme for years.

The consensus is that Mr Rendell believes he missed a chance for national prominence by allowing the two whistleblowers to be fired and sweeping the results of their investigations under the rug. Critics point out that PennMap is still in place even though TMAP has been discredited in Texas and other states.

In November 2005, USA Today quoted FDA Drug Safety Officer, Dr David Graham’s estimate that 62,000 Americans die each year from the off-label prescribing of atypicals. According to Mr Jones, this translates into nearly 10,000 deaths occurring in Pennsylvania during Governor Rendell’s first term.

During a congressional hearing last month, Dr Graham testified that the off-label use of atypicals to sedate people in nursing home kills roughly 15,000 people a year. Based on this estimate, Mr Jones says, about 2,400 Pennsylvania senior citizens died in the Governor’s first term.

“During this time,” Mr Jones reports, “Pennsylvania citizens, insurers and taxpayers paid in the neighborhood of one billion dollars for drugs proven to be no more effective, and far more deadly, than the older antipsychotic medications.”

(essentially the whole article, to catch the flavor….)

Atypical antipsychotics are widely believed to be better tolerated in adults than first-generation, or typical antipsychotics, and more likely to be taken long-term. They are less likely to cause tremors and other serious movement disorders that affect users of typical antipsychotics.

In contrast to the earlier drugs, atypicals usually work onserotoninreceptors in addition to dopamine receptors. Drugs in this group include olanzapine (Zyprexa), clozapine (Clozaril), risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify) and paliperidone (Invega).

The drugs are prescribed for conditions such as schizophrenia and bipolar disorders and may also be given for agitation,anxiety, psychotic episodes and obsessive behaviors. Their off-label use is increasing, and the Food and Drug Administration has now approved Abilify for use in adults who do not respond to antidepressants alone.

The most common side effects include dry mouth, blurred vision and constipation, dizziness or lightheadedness, and weight gain. Sometimes atypical antipsychotics can cause problems sleeping, extreme tiredness and weakness.

With long-term use, atypical antipsychotics can also carry a risk of tardive dyskinesia, a condition involving repetitive, involuntary movements often of the mouth, tongue, facial muscles and upper limbs. Physicians aim to prevent its development by using the lowest effective dose of antipsychotics for the shortest time.

When possible the medication should be stopped, or reduced, if tardive dyskinesia is diagnosed. But the condition may remain for months, years, or even permanently. Its symptoms may be reduced with the drug tetrabenazine (Xenazine), but this drug has been linked with its own side effects, includingdepression, dizziness, drowsiness, insomnia, fatigue and nervousness.

Othermedicationsmay also help tardive dyskinesia, including ondansetron (Zofran) and several anti-Parkinsonian drugs. Benzodiazepines have been tried, but a 2006 review found this treatment “did not result in any clear changes” so routine clinical use is not recommended. Changing to a newer form of atypicalantipsychoticmight be beneficial.

Associate Professor Thomas Schwartz from the Department of Psychiatry at the State University of New York says that the lower-potency atypical antipsychotics, Seroquel, Abilify and Geodon, “are probably associated with the smallest risk for tardive dyskinesia.”

Another possible side effect of atypical antipsychotics is Parkinsonism, a neurological condition involving tremors, hypokinesia (decreased bodily movement), rigidity, and unsteadiness. The risk is lower on Abilify than Geodon, due to their mechanisms of action.

These drugs are also linked with a common neurological movement disorder called dystonia. It involves involuntary and uncontrollable muscle spasms which can force affected parts of the body into abnormal, sometimes painful, movements or postures. Dystonia can be generalized throughout the body, or occur in one place such as the neck muscles, the muscles around the eyes, the face, jaw or tongue, or the vocal cords.

There is currently no cure for dystonia, but there are several popular treatments depending on the type of dystonia and age of onset. As dystonia is a complex and personal condition, the effectiveness of treatment options can vary widely between patients.

One common treatment is regular injections of botulinum toxin, usually repeated every three months. Some oral drugs are also available, including anticholinergic drugs such as trihexyphenidyl which helps control muscle spasms and the tremor by blocking the effect of a chemical messenger in the brain called acetylcholine.

Benzodiazepines are frequently used in the treatment of dystonia. They work by boosting levels of a chemical which inhibits nerve signals in the brain, so act as muscle relaxants. They may trigger sleepiness and sedation if the medication is stopped too rapidly. The GABA agonist baclofen is another muscle relaxant which may ease the muscular spasms and cramps of dystonia, but may cause lethargy, upset stomach, dizziness and dry mouth.

Akathisia, another possible side effect of atypical antipsychotics, is often described as an “inner restlessness” that makes it difficult to sit still or remain motionless. Unfortunately it is often misunderstood and misdiagnosed, sometimes leading to patients reducing or stopping their medication without advice from the physician.

I had a friend with this.  Do you know what it’s called?  Restless Leg Syndrome.  She was also diabetic.  “Symptoms may be worse during stress or emotional upset.”

It may be reduced by decreasing the dose or by changing drugs, but this should always take place under medical supervision. Treatment may include beta-blockers such as propranolol or metoprolol, or benzodiazepines such as clonazepam.

A 2010 review concluded that, “Effective and well-tolerated treatment is a major unmet need in akathisia.” But author Michael Poyurovsky, of the Tirat Carmel Mental Health Center in Israel, added, “Accumulating evidence indicates that agents with marked serotonin-2A receptor antagonism may represent a new class of potential anti-akathisia treatment.” These drugs include cyproheptadine, ketanserin, mirtazapine, nefazodone, pizotifen and trazodone, although none are yet specifically indicated for akathisia.

Rarely {??}}, atypical antipsychotics may trigger diabetes. The cause seems to involve an increase in insulin resistance and changes to insulin secretion. Metabolic syndrome can also be produced by the drugs. The FDA requires all manufacturers of atypical antipsychotics to include a warning about the risks of diabetes and hyperglycemia (high blood pressure).

The risk appears to be highest with Zyprexa and Clozaril. Geodon and Abilify are thought to have the smallest risk. Experts from the Texas Tech University Health Sciences Center in Dallas, say that “periodic monitoring of glucose should be considered” for all patients on atypical antipsychotics.

References

Bhoopathi, P. S. S. and Soares-Weiser, K. Benzodiazepines for neuroleptic-induced tardive dyskinesia.Cochrane Database of Systematic Reviews2006, Issue 3. Art. No.: CD000205

Schwartz, T. and Raza, S. Aripiprazole (Abilify) and Tardive Dyskinesia.Pharmacy and Therapeutics, Vol. 33, January 2008, pp. 32-34.

http://en.wikipedia.org/wiki/Atypical_antipsychotic

www.dystonia.org.uk

Poyurovsky M. Acute antipsychotic-induced akathisia revisited.The British Journal of Psychiatry, Vol. 196, February 2010, pp. 89-91.

Mathys, M., Blaszczyk, A. and Busti, A. Incidence of abnormal metabolic parameters and weight gain induced by atypical antipsychotics in elderly patients with dementia.The Consultant Pharmacist, Vol. 24, March 2009, pp. 201-9.

Drugging the Vulnerable:  Atypical Antipsychotics in Children and the Elderly (May 2011):

What disturbs me — a LOT — about this prescription is that some of the effects they are prescribed for may be normal responses to severe family abuse:  molestation, violence, and seems related to trauma.  So kids come in with trauma, or unable to concentrate in school (ADHD carefully examined often relates to school situations) — and they are being drugged, instead of stopping whatever violence may have caused their distress to start with, thus (when it’s so), there is a profit to violence in the drug industry.   I wouldn’t say this, except I have been a teacher, and also had experience with long-term domestic violence, and stalking afterwards, and yes, it does result in PTSD, just as war often does.

In a presentation this week at an American Psychiatric Association meeting, Dr. John Goethe, director of the BurlingameCenter for Psychiatric Researchin Connecticut, reported that over the last 10 years, more than half of all children aged 5 to 12 in psychiatric hospitals were prescribed antipsychotics — and 95% of these prescriptions were for second-generation antipsychotics.

First of all, let’s look at that center, at least briefly:

http://www.harthosp.org/InstituteOfLiving/Research/BurlingameCenter/default.aspx

Investigational Therapies Service
This service, directed by Drs. John Goethe and Andrew Winokur, offers access to psychiatric medications that are currently in development but not yet approved for use in routine clinical care. These medications can only be administered to individuals who participate in a formal research study. Click here for information about current studies.

Mood Disorders Consultation Service
The Mood Disorders Consultation Service at The Institute of Living is designed to help people whose mood disorders have so far been resistant to therapy. The behavioral health community increasingly recognizes that recovery—not just response—must be the ultimate goal of therapy. Full recovery is the overarching goal of our program. We continue to work with each patient until we have identified the optimal treatment and outcome. (more)

(Back to the original article):

Many of these children didn’t have a condition for which the drugs have been shown to be helpful: 44% of youngsters with post-traumatic stress disorder (PTSD) and 45% of children with attention deficit hyperactivity disorder (ADHD) were treated with them. (More on TIME.com:SPECIAL: Kids and Mental Health)

Pharmacologically, the ADHD prescriptions make no sense: FDA-approved drugs for the condition raise levels of the neurotransmitter dopamine, while antipsychotics do the opposite, lowering them.

Goethe also noted another study that showed that the number of office visits by children and teens that included antipsychotic drug prescriptions rose 600% from 1993 to 2002. “The obvious second-generation bias is very apparent in these data, as is the irrational use of antipsychotics for indications such as PTSD and ADHD for which there is no controlled evidence whatsoever that these are safe or effective treatments,

Here’s a 2001 article from NYU School of Medicine (from PubMed) showing how they knew the atypicals lead to diabetes:

J Clin Psychiatry. 2001;62 Suppl 23:30-8.

Hyperglycemia associated with the use of atypical antipsychotics.

Lindenmayer JP, Nathan AM, Smith RC.

Source New York University School of Medicine, New York, USA.

Abstract

The available literature suggests that patients with schizophrenia are at risk for diabetes mellitus and taking antipsychotic medication further increases the chance of developing non-insulin-dependent hyperglycemia. {{HIGH BLOOD GLUCOSE; cf. DIABETES, potential risks if untreated, unmanaged: diabetic coma and death… }}

Case reports, chart reviews, and some results from clinical drug trials implicate a relationship between glucose levels and treatment with clozapine or olanzapine in patients with schizophrenia, although a few cases of hyperglycemia have also been reported in patients taking risperidone (RISPERDAL) and quetiapine (SEROQUEL). These studies indicate that hyperglycemia is not dose dependent, is reversible on cessation of treatment with clozapine or olanzapine, and reappears on reintroduction of these therapies