Remember Dan Markingson and his mother, Mary Weiss

Today is the 9th anniversary of Dan Markingson's death. My thoughts are with his mother, Mary Weiss. 

A mother's love for her child is like nothing else in the world. It knows no law, no pity, it dares all things and crushes down remorselessly all that stands in its path.

Agatha Christie

via The Star Tribune:

Dan Markingson's Mother Replies to University of Minnesota VP Mulcahy

Posted by: Bill Gleason under Society, Crime, Violence, Disasters, Education and literacy, Continuing education,Government, Politics Updated: March 3, 2011 - 8:19 AM

 

Weeping Angel 

Part of mausoleum of canon Guilain Lucas  (1628)

Photo credit: Wikimedia Commons

Dr. Mulcahy's original letter appeared in the Minnesota Daily.  I'd encourage interested readers to read it as well as my own comments at the end of the article. With the permission of Mary Weiss, I here reprint her letter. It should receive widespread attention in the community.  Steps should be taken, including an independent investigation, to assure that such incidents do not occur in the future.  To argue that what happened is not illegal is a far cry from the Hippocratic Oath: First do no harm.

Mary Weiss writes in today's Daily:

I am Mary Weiss, mother of Dan Markingson, who died while in a University of Minnesota clinical drug study.

In a Feb. 24 letter to the editor published in the Minnesota Daily, “The Markingson case deserves better from the Daily,” R. Timothy Mulcahy, vice president for research at the University, states, among other things, that the University did not profit from the study in which Dan died.

So, this study was revenue neutral? Does the University not profit from their clinical drug research? Who would possibly believe this?

Mulcahy states non-University psychiatrists found no wrongdoing. Of course they found no wrongdoing: These psychiatrists were paid to find no wrongdoing by virtue of the fact that they were “expert witnesses” for the University. Other medial professionals have since disagreed with this
assessment.

Dr. Harrison G. Pope, Jr., professor of psychiatry at Harvard Medical School, said about the study, “There is virtually no evidence that this vulnerable, severely psychotic and mentally incompetent patient was capable of understanding the study to which he was consenting.”

Or take the statement of James I. Hudson, also a professor of psychiatry at Harvard, who summed up his professional opinion of the doctor who conducted the study, saying, “Dr. [Stephen] Olson’s errors, omissions, improper acts and failures were to a reasonable degree of medical certainty, a substantial contributing factor and a proximate cause of Mr. Markingson’s death.”

Dr. Keith A. Horton, licensed psychiatrist in the state of Minnesota, said in his expert testimony, “It is my opinion that this case represents a violation of biomedical standards upon which there is a widespread consensus for informed consent and human subjects’ protection.”

Mulcahy states also in his article, “The University is steadfast in its commitment to the protection of all research subjects.”

If this had been the case, “Dan’s Law” — which was passed unanimously in both the Minnesota House and Senate in 2009 — would have been entirely unnecessary.

This law now prevents anyone on a stay of civil commitment from entering a psychiatric clinical drug study and also prohibits any doctor from putting his or her own patients into his or her own clinical drug study.

Also, Mulcahy states that “proper care was provided” to Dan. I don’t think many people would consider it “proper care” when on April 9, 2004, Easter Sunday — less than a month before he died — Dan was psychotic, and I, his distraught mother, left voice messages for Olson and also Jeanne Kenney, the study’s coordinator.

I said, “Do we have to wait for him to kill himself or someone else before anyone does anything?” thinking for sure someone would call me  back in the morning and re-hospitalize Dan.

Unbelievably, no one responded — though Kenney did write my message verbatim in her study file. Evidently, the outcome of the study was more important than making a patient well or keeping him alive.

Also, Mulcahy states that no laws were violated by the University. In fact, the University was given immunity by a Hennepin County judge who cited the Minnesota law which states “[Minnesota] and its employees are not liable for … a loss caused by the performance or failure to perform a discretionary duty.”

Horton also said, “It is my opinion that no university or medical center should tolerate or condone the improper, coercive, unethical practices documented in the case of Dan Markingson. Correction measures should be instituted to prevent future injuries to vulnerable patients.”

But no correction measures have been taken. And the University still tolerates and condones improper, coercive, unethical practices.

What is it going to take for them to change? I really don’t know. Hopefully not the death of another parent’s precious child.

No laws have been broken? And the angels wept. 

MindFreedom International endorses petition asking the governor of Minnesota, Mark Dayton, to investigate research misconduct!

Dan Markingson and his mother, Mary Weiss
photo via MotherJones

via MindFreedom International:

Forced experimentation on psychiatrically labeled people – think it can’t happen here in the US?  Sadly, evidence indicates it has happened, and that it played a part in at least one death.   MindFreedom International is now endorsing a petition, asking the governor of Minnesota, Mark Dayton, to investigate!

The petition concerns the case of Dan Markingson, a young man labeled and involuntarily committed, who was coerced into an industry-sponsored antipsychotic study at the University of Minnesota in 2003.  A “stay of commitment” order compelled him to obey the recommendations of his psychiatrist, who was conducting the antipsychotic study; his mother attempted to speak up for him, warning that he was doing poorly in the study and was in danger of killing himself, but University of Minnesota researchers ignored her warnings.  On May 8, 2004, Markingson committed suicide. 

Although the case has been highly controversial since it became public in 2008, University of Minnesota officials have repeatedly claimed that the university bears no responsibility for Markingson’s death.  A lawsuit against the university was dismissed on grounds of “sovereign immunity. “  Afterwards, attorneys for the university filed an action against Dan’s mother demanding payment of $57,000 in legal costs.

 Seriously, the university filed a legal action against the mother, rather than look into what went wrong!  They have continued to deny responsibility despite the fact that in 2010, AstraZeneca, the sponsor of the study in which Dan died, settled federal fraud charges for $520 million, and a University of Minnesota psychiatrist appeared to be involved.  Last year, the Minnesota Board of Social Work found serious wrongdoing by the study coordinator for the research study in which Dan died.  It is possible that other research subjects have died or suffered serious injuries, or that they have been mistreated in other ways.

After many unsuccessful attempts to have the case investigated by an external research oversight body, Dan’s mother Mary Weiss and her friend, Mike Howard, have petitioned the governor to appoint an external panel to look into the death and other possible research misconduct in the Department of Psychiatry.   Early supporters of the petition include James Gottstein, the director of PsychRights; Marcia Angell, Arnold Relman and Jerome Kassirer, all former editors of New England Journal of Medicine; Michael Carome of Public Citizen and a former official with the federal Office of Research Protection; and Susan Reverby, the historian who uncovered the US-led syphilis experiments in Guatemala, which led to a presidential apology in 2010. 
The petition has also been signed by over 150 experts in medical ethics, law and health professions. 

Sign the petition at this link:
https://www.change.org/petitions/governor-mark-dayton-of-minnesota-investigate-psychiatric-research-misconduct-at-the-university-of-minnesota-2

To take further action in support for the petition, contact:
Eric Kaler
President, University of Minnesota
202 Morrill Hall 100 Church Street S.E. University of Minnesota ?Minneapolis, MN 554
Email: ekaler@umn.edu
Phone: 612-626-1616 Fax: 612-625-3875

Mark Dayton
Office of the Governor 130 State Capitol 75 Rev. Dr. Martin Luther King Jr. Blvd. ?St. Paul, MN 55155 
Telephone: 651-201-3400 Toll Free: 800-657-3717 
Email: mark.dayton@state.mn.us

For more information on the controversy:
Carl Elliott, “Making a Killing,” Mother Jones
http://www.scribd.com/doc/36883035/Making-a-Killing-by-Carl-Elliott

For more information on MindFreedom’s role in stopping involuntary electroconvulsive therapy on Ray Sandford, a Minnesota resident, see  www.mindfreedom.org/shield/ray-sandford

See also:
Jeremy Olson and Paul Tosto, “Dan Markingson had Delusions,” St. Paul Pioneer Press. http://www.twincities.com/ci_9292549


Andy Mannix, “Charles Schulz under Scrutiny for Seroquel Study Suicide,” City Pages, http://www.citypages.com/2011-02-02/news/charles-schulz-under-scrutiny-for-seroquel-study-suicide/


Media contact for petition: Carl Elliott, ellio023@gmail.com

Please help Mary Weiss find the justice she seeks

He is a poor son whose sonship does not make him 

desire to serve all men's mothers. 

~ Harry Emerson Fosdick

Mothers are the necessity of invention.

~ Bill Watterson

Mary Weiss with her son, Dan Markingson

I have another petition up in the upper right hand corner, the same picture of Mary Weiss and her son Dan Markingson as above--the text of the petition is below... 

Carl Elliott, a bioethics professor at the University of Minnesota, has done a tremendous amount of work attempting to get regulatory authorites to perfom their ethical and legal duties, to investigate and hold accountable the unethical professionals who failed Dan Markingson.  read his post about the petition here

my comment: The ethical failures and medical negligence of doctors Schultz and Olsen are the proximate cause, i.e. an act or failure to act which  resulted in Dan Markingson's death. These two doctors were  unethical, careless and medically negligent.  Why has there been no homicide investigation for what is clearly criminally negligent manslaughter? Plainly, these psychiatrists were aware of the risks, yet they failed to perform essential duties they owed to Dan.  When a patient dies because an unethical doctor is willfully negligent and fails to provide adequate medical care to a vulnerable adult whom the doctor owes both an ethical and legal duty of care to; it is homicide. In my opinion, Dan Markingson is the victim of iatrogenic homicide. 

via Change.org:

Petition by Mike Howard

In November 2003, psychiatrists at the University of Minnesota used the threat of involuntary commitment to force a mentally ill young man named Dan Markingson into a very profitable, industry-funded study of antipsychotic drugs. Dan was enrolled in the study over the objections of his mother, Mary Weiss. For months Mary tried desperately to get him out of the study, warning the psychiatrists that Dan’s condition was deteriorating and that he was in danger of killing himself. The psychiatrists refused to listen to her. On May 8, 2004, Dan committed suicide, and Mary lost her only child.

I feel privileged and humbled to have called Dan my friend. Because of a very unique situation I had a front row seat watching Dan’s resilience as he attempted to overcome not only his original mental and emotional crisis, but also the trauma that occurred when he was betrayed by those who were charged and licensed to provide care, healing and protection. For the past nine years Mary and I have tried unsuccessfully to have the University of Minnesota and its psychiatrists held accountable for Dan’s death. But Mary’s lawsuit against the university was dismissed on a technicality in 2009, and the university used legal threats to force her to give up her right of appeal.

Even so, Mary has refused to back down. In 2009, the Minnesota state legislature passed “Dan’s Law,” which prohibits researchers from recruiting a patient under an involuntary commitment order into a psychiatric drug study. Media outlets such as Mother Jones, the St. Paul Pioneer Press, City Pages and Scientific American have published accounts of Dan’s story. His story was also featured in the documentary film, Off Label. In 2010, AstraZeneca, the sponsor of the study in which Dan died, settled federal fraud charges for $520 million, and a University of Minnesota psychiatrist was implicated. Last year, the Minnesota Board of Social Work found serious wrongdoing by the study coordinator for the research study in which Dan died.

More recently, evidence of fraud and serious privacy violations in psychiatric studies at the university have emerged. It is possible that other research subjects have died or suffered serious injuries, or that they have been mistreated in other ways. Bioethicists at the University of Minnesota itself have called for an external investigation, yet the university still refuses.

I cannot tell anyone else what way of speaking out is most aligned with his or her own personal principles. However, I believe those of us who are personally affected by these issues must break the silence about the human rights violations inherent in coerced participation in psychiatric research. While University of Minnesota researchers used many unethical methods to force Dan to participate in this research study, the most egregious of them was fear. Dan was afraid that there was no alternative to taking part in the study, and that he would face a complete loss of liberty if he did not participate.

Given the repeated failure of university officials to act in good faith, I believe that the Governor of Minnesota, Mark Dayton, should appoint an external panel of experts to investigate ethical wrongdoing in psychiatric research at the University of Minnesota, including the circumstances surrounding Dan’s death. The panel should be given latitude to investigate the University of Minnesota human subject protection program, the Department of Psychiatry, the Office of the General Counsel, and any other university officials involved in the oversight of human research.

Let me finish by allowing Mary Weiss, Dan’s mother, to speak for herself.

Dan and I were very close. I have experienced more anguish than I thought humanly possible since Dan’s death. He had dreams, like everyone. He had a talent for creative writing, and he had hoped one day to write for The New Yorker magazine. Unfortunately, his unfinished life robbed him of this dream. In fact, his short time on earth took many dreams from him, and also from me. The things he wished for, I wanted him to realize. Please demand an investigation into the circumstances surrounding Dan’s death, and help ensure no other family ever suffers such a loss from unregulated and improperly supervised clinical trials. Please sign the petition below. Help us find justice, not vengeance.

Text of the Letter to

To:
Mark Dayton, Governor of Minnesota 

Dear Governor Dayton,

I just signed a petition asking you to investigate possible research misconduct in the Department of Psychiatry at the University of Minnesota.

I am disturbed by the refusal of university officials to investigate the suicide of Dan Markingson in an industry-sponsored research study in 2004. I am also concerned by the university’s refusal to look into the possibility of misconduct in other psychiatric research studies. As a public institution, the University of Minnesota has a responsibility to answer legitimate questions about its research activities and to protect the rights and welfare of research subjects.

I urge you to appoint an impartial, external panel of experts in research ethics and regulation to investigate.

Thank you for your consideration.

Sincerely,
[Your name]

Suicide triggers lawsuit against Veterans Administration

Kelli Marie Grese

via Air Force Times:
Sister’s suicide triggers lawsuit against VA

By Patricia Kime - Staff writer
Posted : Thursday Dec 6, 2012 18:38:38 EST

a few excerpts:

On Veterans Day 2010, former Navy corpsman Kelli Marie Grese, 37, swallowed an unknown quantity of the antipsychotic Seroquel — her fourth suicide attempt in eight months using the same drug.

That time, she succeeded. She never regained consciousness.

Her death is the subject of a $5 million lawsuit filed against the Veterans Affairs Department in the U.S. District Court in Newport News, Va., alleging VA physicians failed to monitor her medications and prescribed them excessively.

Her twin sister, Darla Grese, also a former Navy corpsman, filed the suit, saying physicians at Hampton VA Medical Center, Va., ignored her pleas to quit doling out prescriptions to her sister, a known addict deemed at “moderate risk for suicide.”

“I’m hoping better attention will be placed on how many pills are being written and quantities,” said Darla Grese.

Darla Grese said she filed the lawsuit because she would like to see VA doctors communicate better and pay closer attention to their own patients’ records.

“I don’t understand how a physician can write a prescription for 450 pills and two months later write another prescription for 450,” she said. “Something’s broken. The system is broken.”

Sister’s suicide triggers lawsuit against VA - Air Force News 

hat tip: Carl Elliot

A Seeding Trial: Side Effects of Newer Antipsychotics in Older Adults updated

Trust me I'm a Ducktor

Updated on 12-5-2012

This is a comment that I left on the Mad in America website:

Being unethical doesn’t mean it does not happen. It does. In my opinion, off label prescriptions of psychotropic drugs, particularly prescriptions which are not based on clinical trial evidence, or even minimally supported by data about the drugs’ safety and effectiveness, (which is more common than not, in psychiatry) is Human Experimentation. Calling it “Off Label” instead of calling it what it is, is deceptive; and I believe it is done to deceive. This off label prescribing is theoretically supposed to be based on actual evidence of safety and efficacy, even if it is not from drug trials; the drugs have been in use for a very long time and STILL there is not the evidence available that what is being done in Standard Clinical practice is supported by EVIDENCE. So how the hell did this become a STANDARD PRACTICE? By a using a quasi-democratic process of collaboration and consensus of a few followed by the vote of a few more.  A group of people in effect have determined that voting on their own educated opinions and reaching a consensus is how to develop an "Evidence Base" for psychopharmacology.  Consensus is evidence of agreetment, it is not a substitute for the empirical data required to ethically justify implementing any medical care standard.  It is a dishonest and not at all ethical to use a collection of subjective opinions and observations AS IF they become scientific evidence by virtue of the number or "importance" of the individuals offering them.  Subjective observation is used to SUPPORT objective information NOT replace it... What are the Standards of Care in psychiatry, ie. practice parameters, treatment algorithms, etc. if they are not science-based ethical medical standards?  What the Standards of Care in psychiatry are is an affirmative defense for allegations of medical malpractice. In effect, and in fact, Human Experimentation without the knowledge or the consent of the human participants is standard practice it's "psycho" pharmacology!  

beginning of original blog post

Recently the disappointing outcome of a study using 4 neuroleptic drugs, called "atypical antipsychotics," was reported by UC San Diego and published in the online Journal of Clinical Psychiatry.  When I first read about this study at 1 Boring Old Man's blog, something seemed seriously wrong; but I couldn't put my finger on it right away. After doing a little digging, I realized what was bothering me. It appears the study was a seeding trial, conducted in an (unsucessful) attempt to "legitimize" gain FDA approval for what is being done in standard practice, the off-label prescription use of the drugs known to be ineffective for treating PTSD, Alzheimer's Disease, and Dementia.  All four drugs have an FDA Block Box Warning for increased mortality when used to treat dementia; i.e. dementia is not an FDA approved indication for the drugs used in this trial. Another condition mentioned by the UC San Diego press release is PTSD; PTSD is not an FDA approved indication for the drugs either. In fact, PTSD is not even mentioned among the three conditions listed for intervention with this drug study at ClinicalTrials.gov.

via UC San Diego Health System:

Four Common Antipsychotic Drugs Found to Lack Safety and Effectiveness in Older Adults

some excerpts:

"In older adults, antipsychotic drugs are commonly prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications – schizophrenia and bipolar disorder. The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia, some of which carry FDA warnings on prescription information for these drugs." (emhasis mine) 

The study looked at four atypical antipsychotics (AAPs) – aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal) – in 332 patients over the age of 40 diagnosed with psychosis associated with schizophrenia, mood disorders, PTSD, or dementia. (emphasis mine) 

“Our study suggests that off-label use of these drugs in older people should be short-term, and undertaken with caution,” said Dilip V. Jeste, MD, Estelle and Edgar Levi Chair in Aging, Distinguished Professor of Psychiatry and Neurosciences, and director of the Stein Institute for Research on Aging at UC San Diego.

"Results of the five-year study led by Jeste, who is also current president of the American Psychiatric Association (which was not involved in this research), showed that within one year of treatment, one-third of the patients enrolled in the study developed metabolic syndrome (medical disorders that can increase the risk of cardiovascular disease or diabetes). Within two years, nearly a quarter of the patients developed serious adverse effects and just over half developed non-serious adverse effects." here

The FDA approved indications for the 4 drugs used in this study are here

All of the drugs used in this drug trial have black box warnings from the FDA for causing increased mortality for elderly with dementia. The UC San Diego article states, some of the drugs, "carry FDA warnings."  The actual number of participants enrolled in the trial was 406, according to the ClinicalTrials.gov website; why would the the UC San Diego announcement state there were only 332?  PTSD and mood disorders are not listed with the conditions participants were to be treated for on the Clinical Trials website; schizophrenia, Alzheimer's Disease, and dementia are the conditions listed. The only one that is an FDA approved condition is schizophrenia.  The end points were safety and efficacy, which is standard for an "investigational" drug trial, Clinical Trials.gov states this was an investigational Phase 1 trial for the first few years of the trial.  

On October 18, 2012 "Active Control" was deleted from the list of  design characteristics for this study. The responsible party, Dilip V. Jeste, and UCSD was changed to "sponsor" on the same  date.  On April 11, 2009 the Seroquel arm was discontinued, and the answer for the  "accepts healthy volunteers" question was changed from "NO" to "Yes."  A Data Monitoring Committee was also added at the same time.  On February 29, 2008 the classification for this trial was changed from a Phase 1 drug trial to a Phase 4 drug trial; The lead sponsor was changed from being listed as the NIMH to being listed as UCSD; and Dilip V. Jeste, at UCSD, was listed as now being the responsible party, usually the responsible party the lead investigator, would also be the lead author, but in this case Dilip V. Jeste, the President of the American Psychiatric Association, is said to be the lead investigator but is not the lead author.  This study started with The Veterans Medical Research Foundation as the lead sponsor, then the lead sponsor was the NIMH, and upon the study's conclusion, the VMRF is once again listed as the lead sponsor and the NIMH is listed as a collaborator. 

"The bottom line is no solid evidence-based treatment exists for psychosis or agitation in dementia. Atypical antipsychotics carry a black-box warning for increased risk of death and cerebrovascular events in dementia, although typical antipsychotics appear no safer." Thomas W. Meeks, M.D. and Dilip V. Jeste, M.D. in Beyond the Black Box: What is The Role for Antipsychotics in Dementia? 2008

via Physicians Postgraduate Press:
Use of Clinical Markers to Identify Metabolic Syndrome in Antipsychotic-Treated Patients

Hua Jin, MD; Jonathan Meyer, MD; Sunder Mudaliar, MD; Robert Henry, MD; Srikrishna Khandrika, PhD; Danielle K. Glorioso, MSW; Helena Kraemer, PhD; and Dilip Jeste, MD

J Clin Psychiatry 2010;71(10):1273–1278

10.4088/JCP.09m05414yel

Copyright 2010 Physicians Postgraduate Press, Inc.

Objective: Metabolic syndrome (MetS) is prevalent among antipsychotic-treated patients; however, in psychiatric clinics, scarce resources often limit the feasibility of monitoring all 5 criteria that are necessary for diagnosing MetS. As one goal of the MetS definition is to facilitate the clinical identification of insulin-resistant individuals, other biomarkers of insulin resistance have been explored. However, there are relatively few data from antipsychotic-treated patients, especially on the association between these markers and the clinical MetS diagnosis.

Method: We analyzed data from 196 psychiatric patients over age 40 years enrolled in an ongoing study of antipsychotic-related metabolic effects that began in August 2005. here

Black Box Warning from The U.S. Department of Health and Human Services FDA

Public Health Advisory: Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances

4/11/2005

The Food and Drug Administration has determined that the treatment of behavioral disorders in elderly patients with dementia with atypical (second generation) antipsychotic medications is associated with increased mortality. Of a total of seventeen placebo controlled trials performed with olanzapine (Zyprexa), aripiprazole (Abilify), risperidone (Risperdal), or quetiapine (Seroquel) in elderly demented patients with behavioral disorders, fifteen showed numerical increases in mortality in the drug-treated group compared to the placebo-treated patients. These studies enrolled a total of 5106 patients, and several analyses have demonstrated an approximately 1.6-1.7 fold increase in mortality in these studies. Examination of the specific causes of these deaths revealed that most were either due to heart related events (e.g., heart failure, sudden death) or infections (mostly pneumonia). read the rest here

 via Physician's Post Graduate Press:

Comparison of Longer-Term Safety and Effectiveness of 4 Atypical Antipsychotics in Patients Over Age 40: A Trial Using Equipoise-Stratified Randomization

Hua Jin, MD; Pei-an Betty Shih, PhD; Shahrokh Golshan, PhD; Sunder Mudaliar, MD; Robert Henry, MD; Danielle K. Glorioso, MSW; Stephan Arndt, PhD; Helena C. Kraemer, PhD; and Dilip V. Jeste, MD

J Clin Psychiatry

10.4088/JCP.12m08001

Copyright 2012 Physicians Postgraduate Press, Inc.

Objective: To compare longer-term safety and effectiveness of the 4 most commonly used atypical antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone) in 332 patients, aged > 40 years, having psychosis associated with schizophrenia, mood disorders, posttraumatic stress disorder, or dementia, diagnosed using DSM-IV-TR criteria.

Method: We used equipoise-stratified randomization (a hybrid of complete randomization and clinician’s choice methods) that allowed patients or their treating psychiatrists to exclude 1 or 2 of the study atypical antipsychotics due to past experience or anticipated risk. Patients were followed for up to 2 years, with assessments at baseline, 6 weeks, 12 weeks, and every 12 weeks thereafter. Medications were administered employing open-label design and flexible dosages, but with blind raters. The study was conducted from October 2005 to October 2010.

Outcome Measures: Primary metabolic markers (body mass index, blood pressure, fasting blood glucose, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), percentage of patients who stay on the randomly assigned atypical antipsychotic for at least 6 months, psychopathology, percentage of patients who develop metabolic syndrome, and percentage of patients who develop serious and nonserious adverse events.

Results: Because of a high incidence of serious adverse events, quetiapine was discontinued midway through the trial. There were significant differences among patients willing to be randomized to different atypical antipsychotics (P < .01), suggesting that treating clinicians tended to exclude olanzapine and prefer aripiprazole as one of the possible choices in patients with metabolic problems. Yet, the atypical antipsychotic groups did not differ in longitudinal changes in metabolic parameters or on most other outcome measures. Overall results suggested a high discontinuation rate (median duration 26 weeks prior to discontinuation), lack of significant improvement in psychopathology, and high cumulative incidence of metabolic syndrome (36.5% in 1 year) and of serious (23.7%) and nonserious (50.8%) adverse events for all atypical antipsychotics in the study.

Conclusions: Employing a study design that closely mimicked clinical practice, we found a lack of effectiveness and a high incidence of side effects with 4 commonly prescribed atypical antipsychotics across diagnostic groups in patients over age 40, with relatively few differences among the drugs. Caution in the use of these drugs is warranted in middle-aged and older patients.    here

via ClinicalTrials.gov:

Side Effects of Newer Antipsychotics in Older Adults

Purpose

This study will compare four atypical antipsychotic medications in terms of the risk of specific side effects each of them presents in middle-aged and elderly individuals.

Condition                                                Intervention                                                   Phase
Schizophrenia                                         Drug: Aripiprazole                                         Phase 4
Alzheimer's Disease                                Drug: Olanzapine
Dementia                                                Drug: Risperidone


Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Metabolic Effects of Newer Antipsychotics in Older Patients

Detailed Description:

Atypical antipsychotic medications introduced within the last decade have been used increasingly for the treatment of several types of psychotic disorders and severe behavioral disturbances in older individuals. This trend is primarily due to a decrease in side effects caused by the new medications, as compared to conventional neuroleptic medications. There is a lower risk for developing tardive dyskinesia and extrapyramidal symptoms, both of which are movement abnormalities, with new antipsychotic medications. However, there has been a growing concern that the newer medications can cause a different set of potentially serious adverse side effects. Specifically, they may cause long-term metabolic, cardiovascular, and cerebrovascular effects, which may result in weight gain, diabetes, or stroke. This study will compare four atypical antipsychotic medications in terms of the risk of metabolic, cardiovascular, and cerebrovascular side effects that each presents in middle-aged and elderly individuals.

Participants in this open-label study will be randomly assigned to receive one of three atypical antipsychotic medications: aripiprazole; olanzapine; or risperidone. Although assignment is random, a technique that may reflect the participant's own interests or the researcher's knowledge of relevant participant characteristics will be used to assign the participant to a medication. Dosing will be determined by each participant's psychiatrist. Participants will be followed for up to 5 years to assess the side effects of the study medications, with study visits at baseline, Week 6, and every 3 months thereafter.

Ages Eligible for Study: 40 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: Yes

Criteria
Inclusion Criteria:
DSM-IV diagnosis of a disease or disorder that requires treatment with an atypical antipsychotic medication

Exclusion Criteria:
N/A here

photo credit Just Ducks

The Drugging of U.S. Troops

Broken Warriors is an ongoing series on mental health issues in the military.

via NextGov:

ARMY WARNS DOCTORS AGAINST USING CERTAIN DRUGS IN PTSD TREATMENT

By Bob Brewin April 25, 2012
Flickr user deanslife 

The Army Surgeon General's office is backing away from its long-standing endorsement of prescribing troops multiple highly addictive psychotropic drugs for the treatment of post-traumatic stress disorder and early this month warned regional medical commanders against using tranquilizers such as Xanax and Valium to treat PTSD.

An April 10 policy memo that the Army Medical Command released regarding the diagnosis and treatment of PTSD said a class of drugs known as benzodiazepines, which include Xanax and Valium, could intensify rather than reduce combat stress symptoms and lead to addiction.

The memo, signed by Herbert Coley, civilian chief of staff of the Army Medical Command, also cautioned service clinicians against prescribing second-generation antipsychotic drugs, such as Seroquel and Risperidone, to combat PTSD. The drugs originally were developed to treat severe mental conditions such as schizophrenia and bipolar disorder. The memo questioned the efficacy of this drug class in PTSD treatment and cautioned against their use due to potential long-term health effects, which include heart disorders, muscle spasms and weight gain.

Throughout more than a decade of war in Afghanistan and Iraq, the military services have relied heavily on prescription drugs to help troops deal with their mental health problems during and after deployment. In a June 2010 report, the Defense Department's Pharmacoeconomic Center said 213,972, or 20 percent of the 1.1 million active-duty troops surveyed, were taking some form of psychotropic drug -- antidepressants, antipsychotics, sedative hypnotics or other controlled substances.

The Army, in a July 2010 report on suicide prevention, said one-third of all active-duty military suicides involved prescription drugs.

The FDA approval of Seroquel and Zyprexa for America's Children

TO APPROVE THE NEUROLEPTICS 

ZYPREXA AND GEODON 
HERE IS HOW THE FDA ADVISORY COMMITTEE VOTED: 

FDA Psychopharmacologic Drugs Advisory Committee Hearings

June 9 – 10, 2009

Prepared by S. Fleisher

On June 9 - 10, the FDA Psychopharmacologic Drugs Advisory Committee reviewed the requests from three pharmaceutical companies for medication approval for the treatment of schizophrenia and/or acute mania bipolar in pediatric populations. 

AstraZeneca Pharmaceuticals, LP, requested Seroquel (quetiapine fumarate) be granted FDA indication approval for the treatment of schizophrenia in adolescents ages 13 – 17 and acute treatment of bipolar mania in children and adolescents ages 10-17. 

Pfizer, Inc. requested Geodon (ziprasidone hydrochloride) be granted FDA indication approval for the acute treatment of bipolar mania in children and adolescents ages 10 – 17 years. 

Eli Lilly and Company requested Zyprexa (olanzapine) be granted FDA indication approval for the treatment of schizophrenia in adolescents ages 13 – 17 years of age and acute treatment of bipolar mania in adolescents ages 13 – 17.

On Wednesday, June 10, the Committee members reconvened. The morning began with a presentation by Kenneth Towbin, M.D., AACAP member and Chief, Clinical Child and Adolescent Psychiatry Mood and Anxiety Disorder Program of the NIMH. Dr. Towbin provided the Committee with an overview of the controversial diagnosis of bipolar disorder and the varying characterization of symptoms used to diagnose the disorder. Dr. Towbin stressed the fact that bipolar disorder is real and can be diagnosed in the pediatric population. He also indicated bipolar disorder is very rare in children and adolescents and that more children and adolescents suffer from severe mood dysregulation. The Committee thanked Dr. Towbin for his presentation and assistance in helping them understand the pediatric bipolar disorder diagnosis controversy. The Committee then continued their discussions and questioning of the data presented on Tuesday.

After thorough discussion, the Committee held the following votes. The Committee found that Seroquel had been shown to be effective (17 – Yes, 1-No) and acceptably safe (16 – Yes, 2 – Abstain) for the treatment of schizophrenia; and they found that Seroquel had been shown to be effective (17 – Yes, 1 – Abstain) and acceptably safe (13 – Yes, 5 – Abstain) for the acute treatment of bipolar mania. The Committee was concerned about the metabolic and cardiac side effects of this medication, specifically the increased weight gain, heart rate and blood pressure. The Committee additionally recommended labeling clarifications regarding the use of this medication only for the narrowly defined mania aspects of bipolar disorder and clear indication that this medication not be used for severe mood dysregulation such as chronic irritability, oppositional defiance and hyperactivity. (emphasis mine)

The Committee found that Geodon had been shown to be effective (12 – Yes, 4 – Abstain, 2 – No) for the acute treatment of bipolar mania but no conclusion was delivered regarding the safety of this medication (9 – Abstain, 8 – Yes, 1 – No). The Committee members that abstained were concerned about the lack of long-term data, high QTc prolongation intervals, higher rate of side effects in children ages 10 – 14, and unusual number of trial subjects that were lost in the follow-up phase. 

The Committee found that Zyprexa had been shown to be effective (11 – Yes, 5 – No, 2 – Abstain) and acceptably safe (10 – Yes, 4 – No, 4 – Abstain) for the treatment of schizophrenia; and they found that Zyprexa had been shown to be effective (17 – Yes, 1 –  Abstain) and acceptably safe (11 – Yes, 4 – No, 3 Abstain) for the acute treatment of bipolar mania. The Committee recommended the approval as a second line treatment and recommended labeling clarifications regarding the use of this medication for the narrowly defined mania aspects of bipolar disorder and clear indication that this medication not be used for severe mood dysregulation. The Committee was concerned about the high level of metabolic and cardiac side effects of this medication, specifically the increased weight gain. (emphasis mine)

AACAP members serving on the Committee included Rochelle Caplan, M.D., Semel Institute for Neuroscience and Human Behavior, UCLA; Masha Rappley, M.D., Michigan State University; Kenneth Towbin, M.D., National Institute of Mental Health; and Benedetto Vitiello, M.D., National Institute of Mental Health.

To view copies of the data and presentations provided during the hearing, please visit the FDA website. (the FDA website no longer has any of this information posted.)

The testimony that is referred to above:

***FINAL***

June 9, 2009

Psychopharmacologic Drugs Advisory Committee Meeting

Food and Drug Administration

5600 Fishers Lane

Rockville, MD 20857

Good afternoon, my name is Larry Greenhill, M.D., and I am President-elect of the American Academy of Child and Adolescent Psychiatry. Over the past 24 months, I have received research support or have worked on a consultant basis with Otsuka, Johnson & Johnson, Forest, Pfizer, and NIMH. I have both practiced child psychiatry, been federally supported to study long-term adverse events associated with psychotropic medication use, and been a member of AACAP for 30 years. AACAP is a professional medical association of 8,000 child and adolescent psychiatrists established in 1953. 

AACAP is the leading national medical association dedicated to treating and improving the quality of life for the estimated 7 - 12 million American youth under 18 years of age who are affected by emotional, behavioral, developmental and mental disorders. Bipolar and Schizophrenia are severe psychiatric illnesses which first appear in childhood and adolescence. No one treatment option works for all children and adolescents with these disorders so we support a wide array of treatment options being available.

Although a few clinical trials have suggested that these antipsychotic medications can be effective in pediatric populations, the lack of systematically collected safety data when youth are exposed for long periods of time, that may affect development strongly, indicates that large scale Phase IV studies need to be carried out. 

We ask the FDA Advisory Committee to carefully consider whether the number and scope of the clinical trials as well as the duration of the safety trials to date involving children and adolescents justifies the labeling changes being requested today. While these medications may be helpful and even life saving for some children and adolescents suffering with these disorders, there are significant metabolic and cardiac adverse events associated with their use. We advise the FDA not to approve the request for indications in these medications unless they are also requiring that children treated be entered into a registry. These registries can take advantage of large group-practice HMO settings where electronic health records and pharmacological prescription data can be aggregated and compared. The resulting systematically collected information on the risks and benefits of these medications as well as specific methods for effective monitoring of their associated side effects must be made available to the public before direct-to-consumer marketing should be permitted to occur.  (emphasis mine) 

We thank the FDA for the opportunity for the American Academy of Child and Adolescent Psychiatry to provide this testimony. 

via National Injury Board News article FDA Considers Psychiatric Drugs For Kids June 2009

on the AACAP website

source of medical monkeys 

Seeding Trials planned in an effort to validate current clinical practice

On April 27th I wrote about the Army's Surgeon General, warning against the use of neuroleptic and other psychotropic drugs to treat the symptoms of PTSD. Today, I see a link to Army launches study of PTSD Meds on the Mad in America site---I can't help but think this is a response to the Army Surgeon General's office backing away from it's long standing endorsement of using psychotropic drugs to treat PTSD. Herbert Coley, civilian chief of staff of the Army's Medical Command issued a memo citing lack of efficacy and the serious risks of using neuroleptic and other addictive neurotoxins as the reason for issuing a warning against using psychiatric drugs to treat PTSD. This current announcement was made initially at the American Psychiatric Association's meeting in Philadelphia on May 5th by Army Maj. Gary Wynn of the Walter Reed Army Institute of Research and Col. David Benedik, associate director for the Center for the Study of Traumatic Stress at the Uniformed Services University of the Health Sciences, and reported in Air Force Times appears to be announcing a plan to conduct 'seeding trials.' Seeding Trials are drug trials conducted with the primary goal of validating 'off-label' prescribing practices, gaining FDA approval to use a drug for a different symptom, and EXPAND THE DRUG MARKET. Obviously, this is unethical, This decision announced at the APA convention should be recognized as a decision to continue serving the profit interests of the drug industry, it cannot be a decision made with the well-being and recovery of Veterans experiencing PTSD as the primary focus. I wonder if Veteran's recovery was considered at all...

I cannot help but be amazed at how openly it is being acknowledged that the drugs used 'off-label' to treat PTSD without any definitive evidence to support using the drugs this way; is in fact a Standard Practice.  Using psychiatric drugs 'off-label' is not a decision  based on objective scientific data or ethical medical standards; it is based on Standard Practices and practice parameters which were adopted in the absence of objective, empirical evidence to support or validate them; ignoring fundamental, ethical medical principles.  Specifically, the principle that treatments used in Standard Practice are supposed to be derived from valid evidence of efficacy...including a risk profile which is justified by the actual benefits achieved.  The article in the Air Force Times makes it crystal clear that the treatment of PTSD for Veterans with neurotoxic psychiatric drugs is not now, and has never been based on Scientific Evidence or sound medical judgement.  

It is Human Experimentation to use drugs or other  treatments without valid evidence of effectiveness  and safety... This means that ethical medical principles are not being used when psychiatric drugs are prescribed 'off-label.'   Psychiatric treatment using drugs "off-label" that is not based on any valid or relevant evidence ignores sound medical reasoning altogether.  Small wonder the  bio-disease paradigm is an abject failure in terms of providing ethical, effective patient-centered care. Ethical clinical care requires that treatment decisions be based on ethical medical principles.  Fundamental principles of providing ethical clinical care require a clinician's primary focus be the individual patient's best interest.  This requires an honest dialogue which is respectful and honest. A professional has a duty to fully inform the patient about the diagnosis and the treatment options, which includes doing nothing; i.e. no treatment.  Informed Consent must be obtained without coercion or fraudulent claims and informing the patient about the potential risks and the possible benefits truthfully; and includes supporting the person who makes the decision to consult others of their own choosing.  Informed Consent is obtained prior to treatment starting, and is it is not a final decision; but is supposed to be an ongoing dialogue. Consent can be withdrawn without fear of or threat of punitive action, coercion or abuse of authority.

Three sentences in the article in particular indicate that treatment of PTSD with psychiatric drugs is without scientific validity; making it experimental treatment:

1. "But little data exists on which “off-label” medications work and which don’t."  

2. "Physicians still assess their patients and treat their symptoms based on their own medical experience as well as patient history and treatment preferences." 

3. “We’re trying to advance the science to catch up with clinical practice,” Wynn said. “This effort will seek to provide clinicians with a higher level of evidence when choosing a drug.” 

Theoretically, treatments used in Standard Practice are derived from scientific evidence, e.g. BASED on empirical evidence that a drug is safe and efficacious treatment for the condition it is being prescribed for; with the data supported by subjective observation and opinion.  In the biomedical paradigm of psychiatric care, standard treatment recommendations are overly reliant upon and sometimes entirely derived from subjective opinions.  A consensus of even well-educated opinions is no substitute for scientific evidence, and pretending that it is is ethically and morally reprehensible.   Clinical treatment "standard practices" are often not supported by the evidence; in some cases, the treatment is contraindicated by the clinical trial data making it unethical and unnecessarily risky. 

Psychiatry is using a bio-medical paradigm not grounded in valid research findings

or based on ethical medical principles.

  

via Air Force Times: 

By Patricia Kime - Staff writer
Posted : Tuesday May 8, 2012 16:21:49 EDT

Military and Veterans Affairs Department physicians often prescribe medication to ease the symptoms of combat-related post-traumatic stress disorder, even though only two antidepressants — Paxil and Zoloft — are approved specifically by the Food and Drug Administration to treat the disorder.

But little data exists on which “off-label” medications work and which don’t. 

The Army is hoping to change this, launching a major research initiative next year on the effectiveness of commonly prescribed medications for PTSD.

Speaking at the American Psychiatric Association meeting in Philadelphia on Monday, Army Maj. Gary Wynn of the Walter Reed Army Institute of Research and Col. David Benedik, associate director for the Center for the Study of Traumatic Stress at the Uniformed Services University of the Health Sciences, said the service will start clinical trials next year to evaluate commonly prescribed PTSD medications such as the antidepressant Cymbalta, mirtazapine, prazosin, and atypical antipsychotics like Seroquel.

VA and the Defense Department published joint guidelines in 2010 to provide doctors with assessments of the known research on many psychiatric medications used for PTSD.

But the guidance, which recommends strongly against the use of benzodiazapines like Valium and Xanax and several other medications, is not absolute. Physicians still assess their patients and treat their symptoms based on their own medical experience as well as patient history and treatment preferences.

Often this means prescribing medications developed to treat other mental conditions.

The Army research will test commonly prescribed medications over the next several years at multiple sites with hundreds of service members and veterans.

“We’re trying to advance the science to catch up with clinical practice,” Wynn said. “This effort will seek to provide clinicians with a higher level of evidence when choosing a drug.”

Wynn and Benedik hope their efforts will lead to better treatments for PTSD in both combat veterans and civilians.

“For pharmaceuticals that show benefits in treating combat-related PTSD, the Department of Defense may work toward a new indication or change in labeling,” Wynn said.

Published results from the first trial are expected by 2016.

First-Line Pharmacological Treatment For PTSD: Developed From Insufficient Evidence

Do neuroleptics like Seroquel and Risperdal, have a valid medical purpose used "off-label"?

Champions of Change? God Bless America and Protect Her Defenders...

FYI: