Blowing Smoke: Smoking Cessation and Drug Safety

BLOOMBERG VIA GETTY IMAGES

via Journal of Clinical Psychiatry:

A Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Varenicline for Smoking Cessation in Patients With Schizophrenia or Schizoaffective Disorder

Jill M. Williams, MD; Robert M. Anthenelli, MD; Chad D. Morris, PhD; Joan Treadow, RN, BSN; John R. Thompson, PhD; Carla Yunis, MD, MPH; and Tony P. George, MD

J Clin Psychiatry 2012;73(5):654–660

10.4088/JCP.11m07522

Copyright 2012 Physicians Postgraduate Press, Inc.

Objective: Effective smoking cessation treatments are needed for patients with schizophrenia, who, compared with the general population, have high rates of cigarette smoking and more difficulty quitting. We evaluated the safety and efficacy of varenicline for smoking cessation in outpatients with stable schizophrenia or schizoaffective disorder.

Method: In this 12-week, randomized, double-blind, multicenter trial (May 8, 2008, to April 1, 2010), 127 smokers (≥ 15 cigarettes/d) with DSM-IV–confirmed schizophrenia or schizoaffective disorder received varenicline or placebo (2:1 ratio). The primary outcome was safety and tolerability of varenicline assessed by adverse events frequency and changes in ratings on the Positive and Negative Syndrome Scale and other psychiatric scales from baseline to 24 weeks. Abstinence was defined as no smoking 7 days prior to weeks 12 and 24, verified by carbon monoxide level.

Results: Eighty-four participants received varenicline; 43, placebo. At 12 weeks (end of treatment), 16/84 varenicline-treated patients (19.0%) met smoking cessation criteria versus 2/43 (4.7%) for placebo (P = .046). At 24 weeks, 10/84 (11.9%) varenicline-treated and 1/43 (2.3%) placebo-treated patients, respectively, met abstinence criteria (P = .090). Total adverse event rates were similar between groups, with no significant changes in symptoms of schizophrenia or in mood and anxiety ratings. Rates of suicidal ideation adverse events were 6.0% (varenicline) and 7.0% (placebo) (P = 1.0). There was 1 suicide attempt by a varenicline patient with a lifetime history of similar attempts and no completed suicides.

Conclusions: Varenicline was well tolerated, with no evidence of exacerbation of symptoms, and was associated with significantly higher smoking cessation rates versus placebo at 12 weeks. Our findings suggest varenicline is a suitable smoking cessation therapy for patients with schizophrenia or schizoaffective disorder.

Trial Registration: ClinicalTrials.gov identifier: NCT00644969

J Clin Psychiatry 2012;73(5):654–660

© Copyright 2012 Physicians Postgraduate Press, Inc.

Submitted: November 8, 2011; accepted February 28, 2012(doi:10.4088/JCP.11m07522).

Corresponding author: Jill M. Williams, MD, UMDNJ-Robert Wood Johnson Medical School, 317 George St, Ste 105, New Brunswick, NJ 08901 (williajm@umdnj.edu). here

I can't help but be suspicious of the conclusion offered in this article. "Varenicline was well tolerated, with no evidence of exacerbation of symptoms."  This conclusion definitely helps secure a place in the market for Chantix as a stop smoking aid for people with a diagnosis of schizophrenia or schizoaffective disorder. What is strange is the trial was conducted at nine different sites.  Why? There were only 128 participants...This article only mentions one suicide attempt; it does not mention any incidences of adverse effects commonly associated with Chantix.  The  trial was conducted by Pfizer, in it's own facilities, the primary outcome measure was safety, and no safety issues were identified in the study. 

This trial trial was conducted for the primary purpose of exploiting psychiatric patients as a means to an end, the end being increasing the market for Chantix, to fulfill Pfizer's marketing agenda... It's obvious from reading this, they expected to have serious safety problems; yet luckily for Pfizer's marketing department and for Pfizer it's stockholders, there was, the authors state, "no evidence of problems." Pfizer found no evidence that Chantix can cause and/or exacerbate psychosis, as is well-documented in the FDA AERS data.

According to the FDA Adverse Event Reporting System: CHANTIX had the highest number of adverse events reported to the FDA for psychiatric symptoms in the second quarter of 2010. The reason? Increased levels of hostility, aggression, and increased symptoms of psychosis... 

via The Institute For Safe Medication Practices:

QuarterWatch: 2010 Quarter 2

Monitoring MedWatch Reports

January 27, 2011

Signals for Varenicline, Levofloxacin and Fentanyl

Varenicline (CHANTIX) 

Safety Problems Continue

"Despite a prominent boxed warning, a mandatory Medication Guide for every patient and declining use, the stop-smoking drug varenicline (CHANTIX) continued to account for large numbers of reported serious psychiatric side effects. In the second quarter the drug was suspect in more possible cases of hostility-aggression, depression and psychosis than any other monitored drug." here

31 Prescription Drugs Are Linked to 387 Homicides 

and 1,527 acts of violence... 

via PLoS ONE:

Prescription Drugs Associated with Reports of Violence Towards Others
Moore TJ, Glenmullen J, Furberg CD (2010) Prescription Drugs Associated with Reports of Violence Towards Others. PLoS ONE 5(12): e15337. doi:10.1371/journal.pone.0015337
a couple of excerpts:
"These data provide new evidence that acts of violence towards others are a genuine and serious adverse drug event that is associated with a relatively small group of drugs. Varenicline, which increases the availability of dopamine, and serotonin reuptake inhibitors were the most strongly and consistently implicated drugs."

"This study, however, contains numerous features intended to minimize the limitations of adverse event data from postmarketing surveillance. The proportional reporting ratio takes into account two possibilities: a) that wider use or a higher reporting rate exposes a drug to a greater chance of having a violence case attributed, and b) that a higher number of reports might have occurred by chance. The varying results among drugs for smoking cessation and the mood stabilizers show it is unlikely that the violence events are attributed to existing problems in the patient populations treated. Also, the focus of this study was on specific event terms that unequivocally described a violent act or thought – such as homicide or physical assault. By excluding more general adverse event terms such as “aggression” or “anger” many thousands of less specific cases were eliminated under the study criteria. While this means that the study did not count many possible cases of violence towards others (a loss of sensitivity) the restrictive criteria increased specificity. However, given that violent thoughts or actions are not typically attributed to drug therapy or recorded in medical records, the reporting rate for violence cases could be very low. The selected violence cases do not provide a reliable estimate of how often they might occur."

The SSRIS with the most reports of adverse events between 2004 and September 2009 were Prozac with 72 reports for violence defined as homicide, homicidal ideation, physical assault, physical abuse or violence related symptoms; Paxil had 177. read here

picture found at Time Healthland

Quack Back: Determining Real Effects of Ducktors Quacking Out Loud

Ducktor Quack

Fredric Neuman, M.D. in Dollars for Docs here & here (free meals from Eli Lilly, maker of Prozac)

via Psychology Today:Fighting Fear
Confronting phobias and other fears.
"Determining the Real Side-Effects of Drugs."
Published on June 28, 2012 by Fredric Neuman, M.D.  

excerpts:

"There are many people who worry excessively about their health. They carry various diagnoses: hypochondriasis, somatization disorder, obsessive-compulsive disorder, and, often, depression. It turns out that these same people worry considerably about drugs and their side-effects, often to the point where they take untested, but “natural” substances, rather than drugs that the manufactures have spent hundreds of millions of dollars testing. I run groups treating these cases of “health anxiety.” There is an exercise I like to conduct in these classes. I take down a glossy pamphlet which is marked “Prozac” on the outside. I ask the group, “would you be willing to take a drug that has these side effects?” and I read to them out loud from the pamphlet:

"Headache—15.5% of all the patients taking this drug. Nervousness—8.5% Insomnia—7.1% Drowsiness—6.3% Anxiety –5.5% Nausea—10.1% Diarrhea—7.0% Dry Mouth—6.0%
Sweating—3.8%

"Usually, by the time I get half-way through this list, they are shaking their heads, “no.”

"Then I tell them that I have been reading from the list of side-effects in the placebo arm of the study! These are the side-effects patients get when they take a sugar pill that they think might be the real pill. Of course, my patients, who are especially suggestible, are still more likely to develop these placebo responses." (emphasis mine)

I started this post without reading the entire article; because I determined that I would write about the article because of my gut reaction to a tweet shared in my twitter feed this evening: "@psychfeed Determining the Real Side-Effects of Drugs.: There are many people who worry excessively about... bit.ly/N0aXtc (via @PsychToday)" I responded by tweeting back: "@psychfeed If the author is being honest, and this is how he has treated a patient; I would say he is unethical, and possibly sadistic..." Then I started this post, posted the links and the excerpts from the article above. THEN, I finished reading the article. NOW I have absolutely no doubt the author is sadistic; and unethical.

The cavalier attitude the author seems to have is troubling for a number of reasons, however, I will keep my critique to two of them. First, it seems that the author has an apparent lack of respect for his patients as people in distress who come to him for help in dealing with their problems. Second, if this article is representative of his 'expert knowledge' about Prozac, also known as fluoxetine, or Serafem, and SSRIs in general; he is ill-informed about the potential risks involved with taking Prozac.  I do not believe that 'side-effects' is an accurate term which describes the serious negative effects people can experience.   The term is only descriptive of the negative effects a person who also experiences a measurable benefit, i.e. by having a reduction in symptoms the drug was taken for.  When there is no appreciable benefit experienced by a patient taking an SSRI, or any other psychiatric drug, the effects which are unwanted, negative effects are not 'side-effects' and calling them 'side-effects' is dishonest; it is a gross mis-characterization of adverse effects that can be debilitating and fatal.

more excerpts from the article:
"So, that leaves the question, what are the real side-effects of Prozac? I read from a second list, the patients who were taking Prozac:

"Headache—20.3% about one third higher than the placebo-responders. Therefore, there is a tendency (slight) for Prozac to cause headaches.

"Nervousness—14.9% again, about one third higher than the placebo-responders. Therefore, there is a real tendency for the drug to cause nervousness. (Usually, this effect disappears in about 3 weeks.)

"Nausea—21.1% vs. 10.1 % for placebo responders. There is, therefore, a distinct tendency for nausea to come from taking Prozac. (This symptom, too. is likely to go away after three weeks.)

"Diarrhea—12.5% vs.7.0% for placebo responders, indicating a mild tendency for Prozac to cause diarrhea.

"Sweating-- 8.4% vs. 3.8% for placebo responders. A very mild tendency to cause sweating.

"All the other side effects for Prozac are close in range to the side-effects in the placebo groups, indicating that the drug does not cause these side-effects. (Any more than a sugar pill would.)

"What does all this mean? It means, first of all, that someone who develops these side-effects upon taking a new drug may not be reacting to the drug itself! They may be reacting to the idea of the drug. Yet, if a patient is told that the particular physical reaction they are having after taking the drug cannot be reasonably attributed to the effect of the drug itself, they often become offended." here

It ALSO means Dr. Neuman, that you seem to believe that it is acceptable for you invalidate your patients; and to minimize or dismiss altogether their complaints. Complaints that, you should be cognizant of having an ethical duty to pay careful attention to. Whether you believe the complaints to be valid or not; what is important or relevant to your patients, should merit more than your contempt and ridicule. The complaints ARE real to your patients doctor; and your patients should have your respect---you ARE working FOR them... Based on this article, it does not seem as if you have much respect for your patients. It is apparent from this article that it is acceptable to you to have less than a respectful, forthright, open and honest dialogue with your patients about the drugs you prescribe to them. One wonders, do you consider patients unworthy of your respect? I ask, because it seems that you have a callous attitude about your patients' need for reassurance, and a lackadaisical attitude about providing pertinent information to them...

This lackadaisical attitude is alarming. Your remarks evince far too casual an attitude about your ethical duty to your patients. Specifically, the ethical duty to provide accurate, appropriate and complete information to your patients so that they are able to give Informed Consent prior to actually follow your professional advice and treatment recommendations! So, I find it very strange that you ridicule your patients' need for reassurance. In light of the biased clinical trial research conducted; the ongoing fraudulent reporting of incomplete and/or biased trial data; and the fraud underlying the FDA-approval process as well as the illegal marketing of Prozac and the other SSRIs; your attitude is despicable.

Are you unaware or willfully blind?  Patients have experienced grievous irreparable harm caused by Prozac and other SSRIs; patients who often were misled about the safety and the efficacy of the drugs. Some people in fact come to mistrust psychiatric professionals and be called paranoid and for being downright suspicious.  Psychiatric patients are offered no commiseration, understanding or empathy from most professionals.  They are not respected, but are invalidated for having their suspicions; and feelings of mistrust grow.  Even though these suspicions, attitudes and feelings are a direct result from having been misinformed, disrespected, and sometimes, coerced and manipulated, they are treated as if they are 'a problem patient' who is simply being non-compliant because they 'lack insight.'  What a freaking racket...Whether the author is or is not aware of these realities faced by patients who have been harmed; and witnessed by those who love them, and are also labeled as lacking insight for supporting and validating the patient; the author's attitude is strange, and wholly inappropriate for a healer/doctor who is treating emotionally fragile people. I can assure the author, and every other professional, that the patients who have experienced lasting harm; the family members who grieve the loss of a loved one; and the family members who care for a loved one; find your cavalier attitude insulting. Your callous disregard for psychiatric patients whom you treat is morally reprehensible.

via PLoS ONE:
Prescription Drugs Associated with Reports of Violence Towards Others

Thomas J. Moore 1, Joseph Glenmullen 2, Curt D. Furberg 3
1 Institute for Safe Medication Practices, Alexandria, Virginia, United States of America, 2 Department of Psychiatry-Cambridge Hospital, Harvard Medical School, Cambridge, Massachusetts, United States of America, 3 Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America

The article's ABSTRACT in it's entirety:
Context
Violence towards others is a seldom-studied adverse drug event and an atypical one because the risk of injury extends to others.

Objective
To identify the primary suspects in adverse drug event reports describing thoughts or acts of violence towards others, and assess the strength of the association.

Methodology
From the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) data, we extracted all serious adverse event reports for drugs with 200 or more cases received from 2004 through September 2009. We identified any case report indicating homicide, homicidal ideation, physical assault, physical abuse or violence related symptoms.

Main Outcome Measures
Disproportionality in reporting was defined as a) 5 or more violence case reports, b) at least twice the number of reports expected given the volume of overall reports for that drug, c) a χ2 statistic indicating the violence cases were unlikely to have occurred by chance (p<0.01).

Results
"We identified 1527 cases of violence disproportionally reported for 31 drugs. Primary suspect drugs included varenicline (an aid to smoking cessation), 11 antidepressants, 6 sedative/hypnotics and 3 drugs for attention deficit hyperactivity disorder. The evidence of an association was weaker and mixed for antipsychotic drugs and absent for all but 1 anticonvulsant/mood stabilizer. Two or fewer violence cases were reported for 435/484 (84.7%) of all evaluable drugs suggesting that an association with this adverse event is unlikely for these drugs." (emphasis mine)

a couple of excerpts from the full article:
"The next drugs most often linked to unprovoked violent outbursts--some resulting in murder--are 11 of 13 SSRI antidepressants. These not so, "magic bullets," whose mode of action (reuptake inhibition) increases serotonin, were involved in 578 cases of violence."

"Two drugs within the SSRI class--Prozac and Paxil--have been linked to the greatest number of reported cases of violence toward others: Prozac ranks 10.9 in the PRR, with 72 reported cases of violence, and Paxil (Paroxetine) ranks 10.2 in PRR, with 177 reported cases of violence."
emphasis mine here

via numbdoc1:
"Dr. David Healy speaking at a Press Conference prior to the 2006 FDA Advisory Committee Public Hearing on the connection between antidepressants and suicidal thoughts and actions. The press conference was put together by the family of Woody Witczak. This clip is part 2 of 3. I shot this clip while in Washington DC working on my documentary, NUMB." www.numbdocumentary.com

via SSRI Stories:
Just a small sample of the cases listed at the link above:

School Shooting Prozac WITHDRAWAL 2008-02-15 Illinois ** 6 Dead: 15 Wounded: Perpetrator Was in Withdrawal from Med & Acting Erratically

School Shooting Prozac Antidepressant 2005-03-24 Minnesota **10 Dead: 7 Wounded: Dosage Increased One Week before Rampage

School Shooting Paxil [Seroxat] Antidepressant 2001-03-10 Pennsylvania **14 Year Old GIRL Shoots & Wounds Classmate at Catholic School

School Shooting Zoloft Antidepressant & ADHD Med 2011-07-11 Alabama **14 Year Old Kills Fellow Middle School Student

School Shooting Zoloft Antidepressant 1995-10-12 South Carolina **15 Year Old Shoots Two Teachers, Killing One: Then Kills Himself

School Shooting Med For Depression 2009-03-13 Germany **16 Dead Including Shooter: Antidepressant Use: Shooter in Treatment For Depression

School Hostage Situation Med For Depression 2010-12-15 France **17 Year Old with Sword Holds 20 Children & Teacher Hostage

School Shooting Plot Med For Depression WITHDRAWAL 2008-08-28 Texas **18 Year Old Plots a Columbine School Attack

School Shooting Anafranil Antidepressant 1988-05-20 Illinois **29 Year Old WOMAN Kills One Child: Wounds Five: Kills Self

School Shooting Luvox/Zoloft Antidepressants 1999-04-20 Colorado **COLUMBINE: 15 Dead: 24 Wounded

School Stabbings Antidepressants 2001-06-09 Japan **Eight Dead: 15 Wounded: Assailant Had Taken 10 Times his Normal Dose of Depression Med

School Shooting Prozac Antidepressant WITHDRAWAL 1998-05-21 Oregon **Four Dead: Twenty Injured

School Stabbing Med For Depression 2011-10-25 Washington **Girl, 15, Stabs Two Girls in School Restroom: 1 Is In Critical Condition

School Shooting Antidepressant 2006-09-30 Colorado **Man Assaults Girls: Kills One & Self

School Machete Attack Med for Depression 2001-09-26 Pennsylvania **Man Attacks 11 Children & 3 Teachers at Elementary School

School Shooting Related Luvox 1993-07-23 Florida **Man Commits Murder During Clinical Trial for Luvox: Same Drug as in COLUMBINE: Never Reported

School Hostage Situation Cymbalta Antidepressant WITHDRAWAL 2009-11-09 New York **Man With Gun Inside School Holds Principal Hostage

School Shooting Antidepressants 1992-09-20 Texas **Man, Angry Over Daughter's Report Card, Shoots 14 Rounds inside Elementary School

School Shooting SSRI 2010-02-19 Finland **On Sept. 23, 2008 a Finnish Student Shot & Killed 9 Students Before Killing Himself
 MANY MORE here

Every Parent Who Has a Child or Teenager Needs to Read This!

Leonie Fennel lost her son, Shane Clancy, to suicide in 2009.  She now spends her time working to inform other parents of the suicidal risk of SSRIs; a class of drugs used for depression.  She does this to honor her son's memory.  I can't help but be humbled to know that she is honoring her son's memory by trying to save strangers.  She lost her son and wasn't even aware that committing suicide is a well-known risk of the drug, Cipramil, or Celexa when Shane was prescribed the drug.  After Shane died, Leonie found out that the risk of the drug causing suicidal and homicidal behavior---particularly in young people---was well known to the drug's maker, Lundbeck.  This is a well known serious, negative effect of all SSRI and SSNRI antidepressants.

The Government drug safety regulators approve the drugs and work for the people in the U.S., in the UK, in Ireland and in New Zealand were aware of the fatal risks; and the drugs were approved in each country, with this risk known to the regulators.   Across the globe, regulatory authorities determined they had no duty to inform the general public, or the prescribing professionals, of fatal risks known to be inherent with this class of drug.

Here in the U.S., the FDA claims it hasd no duty to disclose that SSRI and SSNRI drugs can be fatal; it's a "trade secret."  How in the hell can a fatal risk be kept a secret from the people who are prescribed the drugs?  It is the FDA's job to determine whether the drugs are safe and efficacious treatments for the conditions the FDA approves them for.  No treatment is without risks, it is also the FDA's duty to ensure that risks are identified and fully disclosed---period.  How can the identified risks of FDA approved drugs be something that the FDA hides from the American people?  The FDA works for the people, not for the drug companies.  The FDA drug approval process is obviously corrupted by the drug industry negligent .  Time and again, the FDA has failed to protect the American people by approving drugs on insufficient and/or corrupt data. The FDA does not require prescribing professionals to report adverse events associated with FDA approved drugs.  The FDA does not actually require drug makers to do the 'required' after market drug trials on the drugs approved through the PDUFA process.  In effect, and in fact, the FDA has not been fulfilling it's protective or regulatory duties for decades; it continues to fail these duties, with seeming impunity.

Another mother, Maria Bradshaw, lives in New Zealand.  Maria's son, Toran Henry, committed suicide due to a toxic reaction from fluoxetine, also known as Prozac, and Serafem.  Maria, is the co-founder of 'CASPER' or, Community Action on Suicide Prevention Education and Research in New Zealand.  Maria stated, "I'm looking for an end to giving kids who are sad or distressed, drugs that double their risk of suicide. I'm looking for the appalling rate of child suicide in my country to be reduced. I want my son, my only child, to have a legacy and I need to feel I'm still his mother and promoting his best interests and this is the only way I know how to parent a dead child."  


I am humbled by these two mother's tremendous effort to inform other parents about what each of them has  learned after their sons were dead.  These mother's are driven, by the tremendous love they have for their children.  They know that love alone cannot prevent suicide, and they know that what we do not know about prescription drugs puts our children at risk, and can even kill them.   Leonie and Maria know that no parent should grieve the loss of a child because of not being fully informed about known risks.  What these mother's were not told about the drugs prescribed their sons prevented them from protecting their sons from the risk. 

Their sons, Toran Henry and Shane Clancy, will never be forgotten...We all owe Leonie and Maria a tremendous debt of gratitude.  These moms share their stories to warn other parents about drug dangers in hopes of sparing them and their children from experiencing what they have.  I am humbled to know of these remarkable women.  These mothers have experienced tremendous loss due to the betrayal of professionals who abdicated their primary ethical duty when researching, seeking regulatory approval and marketing SSRI drugs.  I am inspired by their tremendous effort for all of us.

Be sure and read the list Leonie has posted on "Lundbeck's Hall of Shame."

Far too many lives have already been lost...

via Leonie Fennel's Blog:

Lundbeck's Hall of Shame
"Since Shane died in 2009 we have tried, and will continue to try, to warn the public that antidepressants can cause suicide and/or homicide. We have Professor Healy’s expert report which states that, in his opinion, Cipramil caused the events of 2009 (It’s attached to the side-bar on the right if anyone needs any information). During the last 2 years and 5 months, we have had to contend with denials and rebuttals from Lundbeck (surprise, surprise) and Ireland’s Psychiatric body, the College of Psychiatry of Ireland; Statements such as this one from Prof. T. Dinan…"
read Leonnie's blog Lundbeck's Hall of Shame


via crookreport.co.uk

photo credit