Zoloft SSRI Antidepressant Destroyed my Life

It’s now August of 2009, just past a year after being discharged from the psychiatric hospital.  I’ve been off Zoloft since March 2009 and am finally feeling like a human being again.  Fortunately, I don’t seem to have any neurological damage, memory impairment, concentration troubles or other lasting symptoms.

I’m 48 years old and my introduction to Zoloft began when I was 34. I’ve since learned that the symptoms of fatigue and difficulty sleeping and concentrating that I was having at that time were due to over-work and adrenal exhaustion. That doctor had me fill out a questionnaire and then spent maybe 10 minutes with me before giving me free samples of Zoloft.   Had I known then, what I know now?… And I must forgive the past and not dwell on it in order to heal.

In June of 2008, my nutritionist who was treating me with amino acid therapy took me off Zoloft abruptly.  This caused me to go into a manic state, which I had never experienced before.  It also brought up a lot of anger.  After about a ten days, my wife and I figured out it was the discontinuation of Zoloft that was causing all these problems, so I went back on it.

Because of all my weird behavior, I had left the house and was staying at a hotel.  My wife got my sister involved and she stayed with me for a couple of days but didn’t bring along her bi-polar medications.  I remember distinctly the night of July 13th:  I slept from about 9pm to 5am, went for a work out and did my meditation.  I was definitely stabilizing.

Then my sister took me into town, my wife and I had another fight and, in my anger and frustration, I broke the rear view mirror off my sister’s car.  This caused her to freak out.  We had picked up her meds and agreed to go back to the hotel and take a nap.  I later learned that she had already called the police.

When we arrived at the hotel, the cops came to my door (hands on their holstered guns) and ordered me out of the car.  They hand cuffed me, searched me and put me in the squad car.  Then, as I later learned, my sister and wife had a discussion about “wether or not to tell the police that I had threatened her.”  My sister told the police a lie, that I had threatened her with a gun and I was hauled off to the ER where I was doped up with an injection.

Later I was taken to the psychiatric hospital where I was asked to sign a bunch of forms and “releases.”  How absurd!  I was only semi-consicouss at the time.

At the hospital I was taken off the Zoloft and diagnosed as bi-polar.  Of course, this through me into another withdrawal episode and made me manic and aggressive again.

I want to point out that I have no history of violence, have never been in any sort of brawl, have never been arrested, have never before been put in handcuffs, no DUI tickets and even a clean driving record.

The hospital changed my drugs every few days.  Zyprexa, Lithium, Depakote, Abilify, etc.  After 20 days, I was discharged. The insurance and family money was expended, so I was well, right?

Far from it:  My wife filed for divorce.  I lost access to my home, which was also my office.  She cleaned out the company bank account, etc.

Eventually, I lost pretty much everything and got saddled with all our debt and received none of the assets due to a waiver of “appearance” I signed 3 days out of the hospital.  We had agreed on a negotiated, one lawyer divorce, but I ended up getting totally screwed.

Over the past 12 months, I’ve lived in 5 states.  I’ve had a couple of “room and board” jobs and stayed with friends.  Fortunately, my mother has been able to give me some financial support, so I haven’t been without the basic necessities of life.  Through a friend, I found Ann Blake-Tracy and she helped me understand what happened to me and gave me phone support while I finished the detox from the Zoloft these past few months.

Now, I’m well enough that I’m looking for  a job again so I can restart my life.

I’m certainly not bipolar.  What a bunch of total bullshit.  All I’m taking right now is 0.5 mg of Klonopin (Clonazepam) twice a day to help with anxiety and sleep.

I used to have a pretty normal life.  I made a six figure income.  My wife (18 years of marriage) didn’t have to work. We had a nice house and the swimming pool I had wanted since I was a child.  Now, all that’s gone.  All because of a stupid little pill and all the people that don’t know what the hell their doing with all these powerful drugs.

During the 13 years I was on SSRI Antidepressants, I saw several different psychiatrists and doctors.  They experimented on me with many different drugs: Effexor, Celexa, Abilify, Alprazolam, Clonazepam (Klonopin), Depakote, Lunesta, Trazodone, Xanax, Zyprexa and of course Zoloft (Sertraline).

Of all the drugs, Lamictal was the worst.  Once the doctor increased the dose from 50 mg a day to 200 mg a day (I’ve since found out that is NOT an increase in accordance with the manufacturers instructions) I had horrible, disgusting nightmares every single night and became highly suicidal.  This happened in October of 2008, and freaked me out so much that I went back on Zoloft and some other drugs so that I could get my sleep.

During all these crazy times, I have survived because of my spiritual faith, the generosity of my mother and some good friends and Divine Grace.  Also, because of the various nutritionists I’ve had over the years, I’ve learned how to eat well and take the right supplements.  Cenitol by metagenics is magnesium supplement that has been especially helpful with relaxing me and helping me sleep.  I order that online at:  http://www.janethumphrey.meta-ehealth.com.

Lastly, I would like to mention that none of these doctors I saw gave me any sort of what I would call informed consent.  I was never informed about all the adverse reactions and side-effects that I’ve now learned were well known back then.  None of the doctors explained that, according to their view of brain chemical imbalance, I would need to stay on these SSRI Antidepressants for the rest of my life.  None of the doctors EVER explained discontinuation syndrome etc, etc, etc.

These drugs manufactures and the doctors that push these drugs are all involved in a horrible scam, the tragic consequences of which yet to become fully manifest.

My intense gratitude to Ann Blake-Tracy and the good work she is doing!

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List of SSRI Antidepressants and Common Psychiatric Drugs

A
Abilify, Adapin, Adderall, Alepam, Alertec, Aloperidin, Alplax, Alprax, Alprazolam, Alviz, Alzolam, Amantadine, Ambien, Amisulpride, Amitriptyline, Amoxapine, Anafranil, Anatensol, Ansial, Ansiced, Antabus, Antabuse, Antideprin, Anxiron, Apo-Alpraz, Apo-Primidone, Apo-Sertral, Aponal, Apozepam, Aripiprazole, Aropax, Artane, Asendin, Asendis, Asentra, Ativan, Atomoxetine, Aurorix, Aventyl, Axoren

B
Beneficat, Bimaran, Bioperidolo, Biston, Brotopon, Bespar, Bupropion, Buspar, Buspimen, Buspinol, Buspirone, Buspisal

C
Calepsin, Calcium carbonate, Calcium carbimide, Calmax, Carbamazepine, Carbatrol, Carbolith, Celexa, Chlordiazepoxide, Chlorpromazine, Cibalith-S, Cipralex, Citalopram, Clomipramine, Clonazepam, Clozapine, Clozaril, Concerta, Constan, Convulex, Cylert

D
Dalmane, Dapotum, Defanyl, Demolox, Depakene, Depakote, Deprax, Deprilept, Deroxat, Desipramine, Desirel, Desoxyn, Desyrel, Dexedrine, Dextroamphetamine, Dextrostat, Diapam, Diazepam, Dilantin, Disulfiram, Divalproex, Dogmatil, Doxepin, Dozic, Duralith

E
Edronax, Efectin, Effexor (Efexor), Eglonyl, Einalon S, Elavil, Endep, Epanutin, Epitol, Equetro, Escitalopram, Eskalith, Eskazinyl, Eskazine, Etrafon, Eukystol

F
Faverin, Fazaclo, Fevarin, Finlepsin, Fludecate, Flunanthate, Fluoxetine, Fluphenazine, Flurazepam, Fluvoxamine, Focalin

G
Geodon, Gladem

H
Halcion, Halomonth, Haldol, Haloperidol, Halosten

I
Imipramine, Imovane

J
Janimine, Jatroneural

K
Kalma, Keselan, Klonopin

L
Lamotrigine, Largactil, Levomepromazine, Levoprome, Leponex, Lexapro, Libritabs, Librium, Linton, Liskantin, Lithane, Lithium, Lithizine, Lithobid, Lithonate, Lithotabs, Lorazepam, Loxapac, Loxapine, Loxitane, Ludiomil, Lunesta, Lustral, Luvox, Lyogen, Lecital

M
Manegan, Manerix, Maprotiline, Mellaril, Melleretten, Melleril, Meresa, Mesoridazine, Metadate, Methamphetamine, Methotrimeprazine, Methylin, Methylphenidate, Minitran, Moclobemide, Modafinil, Modalina, Modecate, Moditen, Molipaxin, Moxadil, Murelax, Myidone, Mylepsinum, Mysoline

N
Nardil, Narol, Navane, Nefazodone, Neoperidol, Norebox, Normison, Norpramine, Nortriptyline, Novodorm

O
Olanzapine, Omca, Orap, Oxazepam

P
Pamelor, Parnate, Paroxetine, Paxil, Peluces, Pemoline, Permitil, Perphenazine, Pertofrane, Phenelzine, Phenytoin, Pimozide, Piportil, Pipotiazine, Pragmarel, Primidone, Prolift, Prolixin, Protriptyline, Provigil, Prozac, Prysoline, Psymion

Q
Quetiapine

R
Ralozam, Reboxetine, Resimatil, Restoril, Restyl, Rhotrimine, Risperdal, Risperidone, Rispolept, Ritalin, Rivotril, Rubifen, Rozerem

S
Sediten, Seduxen, Selecten, Serax, Serenace, Serepax, Serenase, Serentil, Seresta, Serlain, Serlift, Seroquel, Seroxat, Sertan, Sertraline, Serzone, Sevinol, Sideril, Sigaperidol, Sinequan, Sinqualone, Sinquan, Sirtal, Solanax, Solian, Solvex, Songar, Stazepin, Stelazine, Stilnox, Stimuloton, Strattera, Sulpiride, Sulpiride Ratiopharm, Sulpiride Neurazpharm, Surmontil, Symbyax, Symmetrel

T
Tafil, Tavor, Taxagon, Tegretol, Telesmin, Temazepam, Temesta, Temposil, Terfluzine, Thioridazine, Thiothixene, Thombran, Thorazine, Timonil, Tofranil, Trancin, Tranax, Trankimazin, Tranquinal, Tranylcypromine, Trazalon, Trazodone, Trazonil, Trialodine, Triazolam, Trifluoperazine, Trihexane, Trihexyphenidyl, Trilafon, Trimipramine, Triptil, Trittico, Tryptanol

U
V
Valium, Valproate, Valproic acid, Valrelease, Venlafaxine, Vestra, Vigicer, Vivactil

W
Wellbutrin

X
Xanax, Xanor, Xydep

Z
Zamhexal, Zeldox, Zimovane, Zispin, Ziprasidone, Zolarem, Zoldac, Zoloft, Zolpidem, Zonalon, Zopiclone, Zydis, Zyprexa

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Experts: Women are drinking more, DUIs are up 28.8% from 1998-2007

Note from Ann Blake-Tracy: After researching and warning for two decades that this crisis with alcohol consumption would come, I can tell you the reason so many women are now drinking is because they are the main ones taking antidepressants which in turn cause overwhelming cravings for alcohol. And it has long been known that women suffer more adverse reactions to antidepressants than men do.

But why cravings for alcohol? These drugs drop the blood sugar causing cravings for sugar and/or alcohol and NutraSweet. Sugar and alcohol initially bring the blood sugar up quickly causing one to instinctively reach for them in a “self medicating” way because they quickly address the low blood sugar level. The problem with doing this is that both substances then drop the sugar levels even lower than before thus producing a vicious cycle of craving more and more sugar and/or alcohol. (To read the science behind this go to www.drugawareness.org)
Another aspect to this increased use in alcohol being tied to antidepressant use is the fact that antidepressants produce mania or Bipolar Disorder so frequently. (See the research article we posted earlier this week showing that 81% of those diagnosed with Bipolar Disorder have been found to have previously taken antidepressants or Ritalin.)
Initially doctors refused to prescribe the first SSRI, Prozac, because of its strong potential to chemically induce mania. There are several types of mania that are recognized. Many have never even heard of these types of mania. And most do not think of these various types of mania when they hear the term Bipolar. Let’s list just a few to shed some additional light on this drinking problem women, who have always taken more antidepressants than men, have developed since these drugs have become so widespread in use.

Pyromania: A compulsion to start fires
Kleptomania: A compulsion to embezzle, shoplift, commit robberies
Dipsomania: An uncontrollable urge to drink alcohol
Nymphomania and erotomania: Sexual compulsions – a pathologic preoccupation with sexual fantasies or activities

So there it is in black and white plain as day – one of the forms of mania, dipsomania, is described as an “uncontrollable urge to drink alcohol.” Could it be any clearer?

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And look at one of the comments from the article below:
“Younger women feel more empowered, more equal to men, and have been beginning to exhibit the same uninhibited behaviors as men,” said Chris Cochran of the California Office of Traffic Safety.
Does that not describe manic behavior – “empowered” or all powerful with grandiose thoughts of one’s self and “uninhibited”? Those have always been earmarks warning of mania.
Hopefully this news about women and drinking will FINALLY wake America up to what first caught my attention with the use of antidepressants – the OVERWHELMING out-of-character cravings for alcohol that is produced by these drugs. (Find much more additional information on this subject at www.drugawareness.org)
Ann Blake Tracy, Ph.D., Executive Director,
International Coalition For Drug Awareness
Website:
www.drugawareness.org & www.ssristories.drugawareness.org
Author: Prozac: Panacea or Pandora? – Our Serotonin Nightmare
& CD or audio tape on safe withdrawal: “Help! I Can’t Get
Off My Antidepressant!”
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Experts: Women are drinking more, DUIs are up

http://us.rd.yahoo.com/dailynews/ap/brand/SIG=br2v03/*http://www.ap.org

AP – Graphic shows driving under the influence arrests for men and women for 1998 and 2007; includes alcohol-impaired …
By LISA A. FLAM, Associated Press Writer Lisa A. Flam, Associated Press Writer 10 mins ago

NEW YORK – It seemed too horrendous even to imagine. But the case of the mother who caused a deadly wrong-way crash while drunk and stoned is part of a disturbing trend: Women in the U.S. are drinking more, and drunken-driving arrests among women are rising rapidly while falling among men.

And some of those women, as in the New York case, are getting behind the wheel with kids in the back.

Men still drink more than women and are responsible for more drunken-driving cases. But the gap is narrowing, and among the reasons cited are that women are feeling greater pressures at work and home, they are driving more, and they are behaving more recklessly.

“Younger women feel more empowered, more equal to men, and have been beginning to exhibit the same uninhibited behaviors as men,” said Chris Cochran of the California Office of Traffic Safety.

Another possible reason cited for the rising arrests: Police are less likely to let women off the hook these days.

Nationwide, the number of women arrested for driving under the influence of alcohol or drugs was 28.8 percent higher in 2007 than it was in 1998, while the number of men arrested was 7.5 percent lower, according to FBI figures that cover about 56 percent of the country. (Despite the incomplete sample, Alfred Blumstein, a Carnegie Mellon University criminologist, said the trend probably holds true for the country as a whole.)

“Women are picking up some of the dangerously bad habits of men,” said Chuck Hurley, CEO of Mothers Against Drunk Driving.

In New York’s Westchester County, where Diane Schuler’s crash killed her and seven other people last month, the number of women arrested for drunken driving is up 2 percent this year, and officers said they are noticing more women with children in the back seat.

“We realized for the last two to three years, the pattern of more female drivers, particularly mothers with kids in their cars, getting arrested for drunk driving,” said Tom Meier, director of Drug Prevention and Stop DWI for the county.

In one case there, a woman out clubbing with her teenage daughter was sent to prison for causing a wrong-way crash that killed her daughter’s friend.

Another woman was charged with driving drunk after witnesses said she had been drinking all day before going to pick up her children at school. Authorities said the children were scared during the ride, and once they got home, they jumped out of the car, ran to a neighbor’s house and told an adult, who called police. The mother lay passed out in the car, and police said her blood alcohol level was 0.27 percent — more than three times the legal limit.

In California, based on the same FBI figures, women accounted for 18.8 percent of all DUI arrests in 2007, up from 13.5 percent in 1998, according to the California Office of Traffic Safety.

Nearly 250 youngsters were killed in alcohol-related crashes in the U.S. in 2007, and most of them were passengers in the car with the impaired driver, according to the National Highway Safety Administration.

“Drunk drivers often carry their kids with them,” said MADD’s Hurley. “It’s the ultimate form of child abuse.”

Arrests of drunken mothers with children in the car remain rare, but police officers can generally list a few.

In the Chicago suburb of Wheaton, Supreme Court Justice Antonin Scalia‘s daughter was stopped by police after she pulled away from a McDonald’s with three of her kids in the car. She pleaded guilty to drunken driving and was sentenced to 18 months of court supervision.

Sgt. Glen Williams of the Creve Coeur, Mo., police department recalls stopping a suspected drunken driver on her way to pick up two preschoolers.

Sometime later, “she told me it actually changed her life, getting arrested,” he said. “She was forced to get help and realized she’d had a problem.”

The increase in arrests comes as women are drinking excessively more than in the past.

One federal study found that the number of women who reported abusing alcohol (having at least four drinks in a day) rose from 1.5 percent to 2.6 percent over the 10-year period that ended in 2002. For women ages 30 to 44, Schuler’s age group, the number more than doubled, from 1.5 percent to 3.3 percent.

The problem has caught the attention of the federal government. The Transportation Department’s annual crackdown on drunken driving, which begins later this month, will focus on women.

“There’s the impression out there that drunk driving is strictly a male issue, and it is certainly not the case,” said Rae Tyson, spokesman for the National Highway Traffic Safety Administration. “There are a number of parts of the country where, in fact, the majority of impaired drivers involved in fatal crashes are female.”

Schuler’s relatives have denied she was an alcoholic and said they were shocked to learn of her drug and alcohol use before the July 26 crash. The wreck, about 35 miles north of New York City, killed Schuler, her 2-year-old daughter, her three nieces and three men in an oncoming SUV she hit with her minivan. Schuler’s 5-year-old son survived his injuries.

Schuler, a cable company executive, could have had a drinking problem that her family didn’t know about, said Elaine Ducharme, a psychologist in Connecticut who has seen more excessive drinking, overeating, smoking and drug abuse during the recession.

Unlike men, women tend to drink at home and alone, which allows them to conceal a problem more easily.

Because of this, they seek treatment less often than men, and when they do, it is at a later stage, often when something catastrophic has already happened, said Dr. Petros Levounis, director of the Addiction Institute of New York at St. Luke’s-Roosevelt Hospital Center.

“Our society has taught us that women have an extra burden to be the perfect mothers and perfect wives and perfect daughters and perfect everything,” Levounis said. “They tend to go to great lengths to keep everything intact from an external viewpoint while internally, they are in ruins.”

In the current recession, women’s incomes have become more important because so many men have lost their jobs, experts say. Men are helping out more at home, but working mothers still have the bulk of the child rearing responsibilities.

“Because of that, they have a bigger burden then most men do,” said clinical psychologist Carol Goldman. “We have to look at the pressures on women these days. They have to be the supermom.”

And just becoming a parent doesn’t mean people will stop using drugs or alcohol, Ducharme said: “If you have a real addictive personality, just having a child isn’t going to make the difference.”

___

Associated Press writers Solvej Schou in Los Angeles, Mark Tarm in Chicago and Betsy Taylor in St. Louis contributed to this report.


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Kauffman Study – (SSRI) Drugs: More Risks Than Benefits?

Journal of American Physicians and Surgeons Volume 14 Number 1 Spring 2009

SSRI Bombshell by Joel M. Kauffman, Ph.D. Tuesday, March 31st, 2009

Selective Serotonin Reuptake Inhibitor (SSRI) Drugs: More Risks Than Benefits?

Joel M. Kauffman, Ph.D.

ABSTRACT

Anecdotal reports have suggested that selective serotonin reuptake inhibitors (SSRIs) may cause suicidal or violent behavior in some patients. Because of the publicity surrounding certain events, and the numerous lawsuits that have been filed, a review of benefits and risks is needed.

At most 30% of patients receive a benefit from SSRIs beyond the large placebo effect in certain mental conditions, especially depression, according to a recent meta-analysis of published trials. An equally recent meta-analysis of all SSRI trials submitted to the FDA showed a small benefit for the severely depressed patients only. Many early unpublished trials did not show any benefit. Adverse effects are common, occurring in up to 75% of subjects.

Severe adverse effects may be underreported.

Meta- analyses of controlled trials did not include any actual suicides or murders, but only suicidality, some finding, in 1991 and 2007, no evidence even of suicidality.

Other meta-analyses using many of the same trials found that suicidality doubled to 1 in 500 on SSRIs compared with placebo or non-SSRI antidepressants, but did not include any actual suicides or murders. The trial designs were devised by SSRI makers to prevent reports of suicides, by eliminating subjects with the slightest trace of suicidal tendencies. Retrospective studies by others showed actual suicides on SSRIs with a relative risk (RR) of 2–3 compared with non-SSRI antidepressants, with an increased incidence of 123/100,000. Lower doses than the smallest available ones were found to maintain benefits in a majority of patients while reducing risks.

table_03_zoloftbusted1

[PLEASE NOTE THAT THE SSRISTORIES DATABASE REFERRED TO BY DR. KAUFFMAN IN THIS STUDY IS NO LONGER POSTED AT THE URL LISTED ABOVE BUT HAS BEEN MOVED TO THE URL www.ssristories.NET ]

No causal connection between SSRIs and suicide and/or violence has been proved; neither has it been ruled out. Physicians need to be vigilant, and aware of legal precedents that may subject them to enhanced liability when prescribing these drugs. The Genesis of SSRIs Fluoxetine (Prozac in the U.S., see Table 1), introduced in 1988 to combat depression, was the fourth selective serotonin reuptake inhibitor (SSRI) on the U.S. market, after being seriously considered by Eli Lilly as an antihypertensive drug. Unlike the earlier “tricyclics” (amitripyline, clomipramine, dothiepin, imipramine, etc.) and other drug classes, SSRIs acted on the brain to raise levels of the neurotransmitter serotonin without raising the levels of norepinephrine. This was thought to be a benefit in treatment of depression, and later anxiety, panic, social phobia, obsessive- compulsive disorder (OCD) , and many other conditions. The SSRIs listed in Table 1 are among the most frequently prescribed in the U.S., and compete with the five non- SSRIs shown, and others.

ssri-drug-table1

Benefits of SSRIs

A prominent recent meta-analysis of Bridge et al. included 27 trials of SSRIs for three defined mental conditions: major depressive disorder (MDD), OCD, and non-OCD anxiety disorders. Benefits, compared with placebo, were found to be highly statistically significant. For MDD, data from 13 trials showed benefit in 61% vs. 50% on placebo, a gain of 11% absolute (NNT=10), <0.001 for all ages of participants. For OCD, data from six trials showed benefit in 52% vs. 32% on placebo, a gain of 20% absolute (NNT=5), <0.001 for all ages. For non-OCD anxiety, data from 6 trials showed benefit in 69% vs. 39% on placebo, a gain of 30% absolute (NNT=3), <0.001 for all ages. These results represent the maximum expectation of benefit from SSRIs since 22 of the 27 trials were financially supported by SSRI makers, and thus subject to the routinely positive bias of industry-sponsored clinical trials. Jay S. Cohen, M.D., author of the 2001 book , wrote that half his patients did well on fluoxetine, but he noted a high incidence (50%) with side-effects. Cohen also cited a pre-approval study showing that the standard 20 mg per day starting dose helped 65% of patients, while 5 mg helped 54%, so Cohen became one of the pioneers in using lower doses before Lilly made them available. The 1996 entry for paroxetine, at least, confirmed that the 17 most common side-effects were dose-dependent.

In four observational cohort studies of four common SSRIs reported by physicians as part of the prescription-event monitoring program in the UK, with more than 10,000 patients in each drug group, only 36% of the physicians reported fluvoxamine as effective, compared with 60% for fluoxetine, sertraline, and paroxetine. These possible benefit rates, which include the placebo effect, parallel the percentage of patients remaining on the drug for 2 months.

See: Over Dose: the Case Against the Drug Companies

An old trial of placebo for anxious and depressed subjects reduced distress in 43%. Three meta-analyses of the antidepressant literature that appeared in the 1990s independently concluded that two-thirds of the effectiveness attributed to SSRIs is actually placebo effect. In a series of nine controlled studies on hospitalized patients with depression, 57% of those given placebo showed improvement in 2–6 weeks. A 1998 meta-analysis of 47 trials on antidepressant medication including SSRIs indicated that 75% of the response to them was duplicated by placebo. This meta-analysis was criticized on several grounds. Therefore, Irving Kirsch, Ph.D., of the University of Connecticut, with other authors, obtained data submitted to the FDA on every placebo-controlled clinical trial on the six most widely used SSRIs, and published a meta-analysis on 47 trials, finding a small, clinically insignificant effect.

This work was updated in 2008:

Analyses of datasets including unpublished as well as published clinical trials reveal smaller effects that fall well below recommended criteria for clinical effectiveness. Specifically, a meta-analysis of clinical trial data submitted to the U.S. Food and Drug Administration (FDA) revealed a mean drug–placebo difference in improvement scores of 1.80 points on the Hamilton Rating Scale of Depression (HRSD), whereas the National Institute for Clinical Excellence (NICE) used a drug–placebo difference of three points as a criterion for clinical significance when establishing guidelines for the treatment of depression in the United Kingdom. Kirsch et al. concluded that the updated findings from 35 carefully vetted trials suggest that, compared with placebo, the four new- generation antidepressants ( fluoxetine, venlfaxine, nefazodone, and paroxetine) do not produce clinically significant improvements in depression in patients who initially have moderate or even severe depression.

They show statistically significant but clinically minor effects only in the most severely depressed patients. Moreover, the significance of the effect probably is based on a decreased responsiveness to placebo, rather than increased responsiveness to medication. Given these results, the researchers conclude that there is little reason to prescribe new- generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective. In addition, they write that the decreased placebo response in extremely depressed patients, combined with a response to antidepressants comparable to that of less severely depressed patients, is a potentially important insight that should be investigated further.

Even these unimpressive findings exaggerated the benefits of antidepressants. In three fluoxetine trials and in the three sertraline trials for which data were reported, the protocol allowed replacement of patients who, in the investigators’ judgment, were not improving after 2 weeks. The trials also included a 1–2 week washout period, during which patients were given a placebo prior to randomization. Those whose scores improved 20% or more were excluded from the study. In 25 trials, the use of other psychoactive medication was reported. In most trials, a chloral hydrate sedative was permitted in doses ranging from 500 mg to 2,000 mg per day. Other psychoactive medication was usually prohibited but still reported as having been taken in several trials.

Perhaps such considerations led David Healy, M.D., an SSRI expert, to his conclusion that “…these drugs do not convincingly work….” His evidence came from early unpublished clinical trials whose results were revealed to him at FDA hearings. For fluoxetine, Healy noted four trials with a positive result and four without. For sertraline, only one of five early studies showed benefit. Because of the huge placebo effect, 32–75%, most physicians unfamiliar with the studies revealing this effect are likely, in my opinion, to say that one-third to two-thirds of their patients are improved on SSRIs. This would also explain Dr. Jay S. Cohen’s findings on lower doses of fluoxetine.

SSRIs reportedly interact with 40 other drugs to cause “serotonin syndrome.”

This presents as twitching, tremors, rigidity, fever, confusion, or agitation. Serotonin/norepinephrine reuptake inhibitors (SNRIs) also may cause serotonin syndrome by interactions. Most tricyclic depressants do not have these interactions, with the exception of amitriptyline.

In a controlled trial of paroxetine vs. clomipramine sponsored by GlaxoSmithKline, 75% of the subjects had an adverse effect on paroxetine, 21% had a severe adverse effect, and 13% committed a suicidal act (1 in 8). The 1996 entry for paroxetine lists 17 side-effects with an incidence of ≥ 5% for approved doses.

They are: asthenia, sweating, constipation, decreased appetite, diarrhea (up to 15%), dry mouth (up to 21%), nausea (up to 36%), anxiety, dizziness, nervousness, paresthesia, somnolence (up to 22%), tremor (up to 15%), blurred vision, abnormal ejaculation, impotence, and other male genital disorders. Fully 31 additional side effects with an incidence at least 1% greater than placebo were listed, including uncontrollable yawning.

Murder, suicide, and suicidality were NOT [emphasis added] included.

Nor were they on comparable lists for fluvoxamine, or sertraline. For fluvoxamine, suicide were separately listed as “infrequent.”

For fluoxetine, suicidal ideation was listed as a voluntary report not proved to be drug related. For sertraline, suicidal ideation and attempt were listed separately as “infrequent.”

The entry for venlafaxine was: “…the possibility of a suicide attempt is inherent in depression.” Not found in the was weight gain, which Cohen lists as a serious side effect.

Typical dropout rates in recent trials are claimed to be 5% (see below), but these must be short trials, or trials with a run-in period. In a meta-analysis of 62 earlier trials with a total of 6,000 subjects, the mean total dropout rate and the proportion of dropouts due to side effects appear comparable to results in general practice: total dropout rates of between 30% and 70% have been reported by 6 weeks, of which some 30%–40% are attributed to side effects and the rest to failure of treatment. Early findings of severe adverse effects by SSRI makers came to light only after the class was established. Of 53 healthy volunteer studies on fluoxetine, the results of only 12 were openly reported.

From 35 healthy volunteer studies on paroxetine, pre-launch, the results of only 14 appeared. From 35 pre-launch healthy volunteer studies on sertraline, only seven appeared. Among the unpublished trials, there was one in which all volunteers dropped out because of agitation (akathisia). In published work on sertraline, data excluded material on behavioral toxicity, including at least one suicide of a Adverse Effects of healthy volunteer, and in a different trial, 2 of 20 volunteers became intensely suicidal. This last is consistent with the dropout rate of 5% for agitation alone in actual trials. It is also consistent with Lilly’s animal studies, in which previously friendly cats treated with fluoxetine started growling and hissing—an unheeded warning.

Just a year after fluoxetine was introduced, Bill Forsyth of Maui, Hawaii, had taken it for only 12 days when he committed one of the first murder/suicides attributed to any SSRI.

In the same year Joseph Wesbecker killed eight others and himself in a Louisville, Ky., printing plant where he worked, after 4 weeks on fluoxetine. Yet as early as 1986, clinical trials showed a rate of 12.5 suicides per 1,000 subjects on fluoxetine vs. 3.8 on older non-SSRIs vs. 2.5 on placebo! An internal 1985 Lilly document found even worse results and said that benefits were less than risks. Such documents were released into the public domain by Lilly as part of the settlement in the Wesbecker case. Fifteen more “anecdotes” of murder/suicide, three with sertraline, were listed by DeGrandpre.

Lilly’s denials of a link to murder/suicide on national television and elsewhere cited a sponsored meta-analysis in in 1991, which exonerated fluoxetine as a cause of suicidal acts or thoughts without even mentioning actual murder or suicide. This study included only 3,067 patients of the 26,000 in the clinical trials it utilized. None of the trials had a declared endpoint of suicidality.

Some of the trials had been rejected by the FDA. No mention was made that Lilly had had benzodiazepines co-prescribed to minimizethe agitation that had been recognized with fluoxetine alone. The 5% dropout rate for anxiety and agitation (akathisia) would have taken out the most likely candidates for suicide. Nevertheless, the 1991 study had its intended effect. For example, in 2006 a 900-page tome entitled , which was aimed at attorneys, cited this study, and failed lawsuits concerning SSRIs. The 2007 meta-analysis by Bridge et al. may be influenced by indirect conflicts of interest that are hard to prove based on the financial disclosures.

Their paper pooled excess risk above placebo for “suicidal ideation/suicide attempt” from 27 trials. The excess risk was said to be 0.7% and statistically significant across all indications, but significant within each indication. Of the 27 trials, only five were sponsored by the drug maker, and one of these, the 2004 Treatment for Adolescents with Depression (TADS) study of fluoxetine, had the highest rate of suicidality—7% above placebo. Most of the same trials were used in a meta-analysis by the FDA, which found a statistically significant excess risk of 2% (4% vs. 2% on placebo, 1 in 50 more). Bridge et al. used a random-effects calculation, while the FDA used a fixed-effects calculation.

In commenting on the negative findings, Bridge et al. write: “No study [in our meta-analysis] was designed to examine suicidal ideation/suicide attempt as a study outcome, and in fact most trials were conducted in patients who had been carefully screened to exclude youths at risk.” No actual murders or suicides associated with SSRI use were reported. Did the designs of the studies preclude detection or reporting?

The Bridge meta-analysis was not just a vindication of SSRIs, as communicated to the by Gilbert Ross, M.D., Medical Director of the American Council on Science & Health. Ross went further, commenting that the FDA “Black Box warning” (see below) was counterproductive because it was discouraging the use of antidepressants! Ross speculated that the lethal rampage of the Virginia Tech shooter might have resulted from premature cessation of medications.

SSRIs in general have long lifetimes in the body. Fluoxetine and its active metabolite in particular have a half-life of 16 days, according to the 1996 . In a reexamination of trials in which suicides or attempts during the inadequate washout period were not blamed on the drug, it was shown that the relative risk (RR) of suicidal acts ranged from 3 for sertraline to 10 for fluoxetine.

A concurrent meta-analysis of 24 trials by Kaizar et al. utilized Bayesian statistics, a valid choice, in my opinion, because data do not have to follow a Gaussian or normal curve to yield valid results, and this method can be used to revise probabilities to determine whether a specific effect was due to a specific cause. They found an association between SSRI use and suicidality with odds ratios of 2.3 (95% confidence interval [CI] 1.3-3.8), when the diagnosis was MDD, not OCD, anxiety, nor ADHD. Non-SSRI antidepressants were said to have no association with suicide. This supports the FDA’s findings and requirement, as of October, 2004, for a Black Box warning for all SSRIs, to monitor children and adolescents for suicidality. Kaizar et al. were concerned that there were no completed suicides among 4,487 subjects in the trials; that the trial times were too short at median length of 8 weeks; and that in 10 of the 12 MDD studies, Again, there was no citation of actual suicides associated with SSRIs and no citation of Healy’s work.

Healy reviewed epidemiologic studies that have been cited to exonerate SSRIs. One was analyzed by Healy to show a threefold increase in suicidality compared with other antidepressants.While “treatment-related activation” has been considered primarily with regard to suicidality, it can lead to harm to others as well as to self. Healy summarized data on “hostile episodes” provided by GlaxoSmithKline from placebo-controlled trials with paroxetine in subjects of all ages: 9,219 on paroxetine and 6,455 on placebo. The rubric of “hostility” was used in the trial to code for aggression and violence, including homicide, homicidal acts, and homicidal ideation, as well as aggressive events and “conduct disorders.” No homicides were reported from these trials.

Overall, during both therapy and withdrawal, the RR was 2.1 for hostile events. In children with OCD the RR was 17. Separately, in healthy volunteer studies, hostile events occurred in 3 of 271 subjects on paroxetine vs. none of 138 on placebo. In trials of sertraline on depressed children submitted by Pfizer, 8 of 189 subjects discontinued for aggression, agitation, or hyperkinesis (a coding term for akathisia), compared with 0 of 184 on placebo. In clinical practice, the term akathisia has been restricted to demonstrable motor restlessness, but if that is the only effect, it would have been called dyskinesia according to Healy, who cites four studies linking akathisia to both suicide and homicide.

Actual suicides were combined with suicide attempts in a 2005 meta-analysis of 702 trials of SSRIs vs. either placebo or an active non-SSRI control. Studies were rejected if the citation was a review, a result of duplicate publication, too short, crossover, or had no reporting of actual or attempted suicide. The studies meeting the criteria included 88,000 patients. For attempted suicide, the RR was 2.3 for SSRIs vs. placebo (95% CI, 1.14-4.55). The number needed to treat to harm (sometimes called the “reverse NNT”) was 1 in 684. There was no difference in actual suicide. Of the 702 trials, 104 failed to report adverse events below a certain pre-set limit of 3%, 5%, or 10% of patients. Only 493 trials reported dropout rates, with a mean of 29%, and the mean follow-up time was only 11 weeks. Thus, there was clearly gross underreporting of adverse effects. PDR children and adolescents with an elevated baseline risk of suicide were excluded.

Journal of American Physicians and Surgeons Volume 14 Number 1 Spring 2009 9

More importantly, because actual suicides are involved, Healy cited a study by Donovan et al. that demonstrated a RR=3.4 ( <0.01) for SSRIs compared with all non-SSRI antidepressants involving 222 actual suicides, of which 41 were among patients who had an SSRI within a month of their suicide. Also the British Drug Safety Research Unit recorded more than 110 suicides in 50,000 patients taking an SSRI, an incidence of 219/100,000 compared with 96/100,000 for the non-SSRI mirtazepine (Remeron), an increase of 123/100,000, or 1 in 813 (Table 2). Thus the RR for actual suicide in patients taking SSRIs was 2.3 (or 2.8 for paroxetine). Even here, though, no murders were listed.

In another study cited by Healy, Jick et al. reported 143 actual suicides among 172,598 patients taking antidepressants. The relative risk of suicide in patients taking fluoxetine was 2.1, compared with those taking the tricyclic antidepressant dothiepin. The risk was not age-dependent. SSRI makers keep insisting that there will be more suicides if SSRIs are used as frequently as now. But the RR of 2–3 shown in studies is a number that the number of suicides that may have been prevented, so SSRI use is associated with more suicides, not fewer.

The International Coalition for Drug Awareness in cooperation with the Prozac Survivors Support Group has produced a website on which about 1,600 violent incidents associated with SSRI use are described ( www.ssristories.net ). The first column on the type of incident (murder, school shooting, etc.) is a hot link to a publicly available description of the incident, typically a local newspaper article. A selection of 10 entries (rows) is presented here as Table 3. About 360 suicides are tallied as well as about 400 murder incidents, many of which were multiple murders, each linked to 26 not net includesSSRIs Provide 1,600 Anecdotes of Violence SSRI use (Rosie Meysenburg, personal communication, 2008 .

As the number of “anecdotes” exceeds 1,600—hardly a small number—the association of SSRIs with murder/suicide, often combined, must be taken seriously. The SSRI website was searched to find combined murder/suicide incidents attributed to a specific SSRI. There were three for fluvoxamine, four for citalopram, 10 each for paroxetine and sertraline, and 31 for fluoxetine. Where the studies above substantiated suicide from SSRI use, the total on the SSRI website of 48 simultaneous murder/suicide incidents associated with SSRI use ties together SSRIs and murder. Since there were about two murders per suicide, we may infer that the murder rate on SSRIs could be about 250/100,000. Since no clinical trial involving multiple homicides is ever likely to be run, no firmer evidence is likely to be found. Healy noted that much of the evidence for suicide and murder came from the efforts of journalists and lawyers.
Note that the website carries a prominent warning that “withdrawal can often be more dangerous than continuing on a medication.” Nine violent events cited elsewhere—seven court cases of homicide (one attempted) and two assaults—were associated with specific SSRIs: three with paroxetine, three with sertraline, two with fluoxetine, and one with venlafaxine. Skeptics have cast doubt on whether the prescribed SSRIs were actually taken, especially since many medical records of juveniles were sealed. In the Columbine, Colo., shootings the toxicology report showed “therapeutic” levels of fluvoxamine in one of the shooters. The Red Lake, Minn., shooter had fluoxetine found, according to news items referenced on the website.

A 2004 editorial in by Simon Wessely, M.D., a spokes- man for Eli Lilly, and Robert Kerwin, Ph.D, cited only a single paper by Healy as a source of claims of suicidality that have found a receptive media audience. Tellingly, the only study described at length is by Jick et al. on the correlation of SSRI use and “attempted suicide,” in which the rates on dothiepin, amitriptyline, fluoxetine and paroxetine were not statistically different. Actual suicides in this study (seven on SSRIs) were not mentioned by Wessely and Kerwin, nor were the 143 suicides in Jick’s earlier paper. Jick et al. have been supported partially by GlaxoSmithKline and Pfizer. No study that reported actual suicides on SSRIs was described in detail, let alone refuted. Wessely and Kerwin wrote: “The problem is that depression is unequivocally and substantially associated with suicide and self-harm.” True, but this not the truth.

Table 2. Suicides Related to SSRIs or Mirtazapine

table_02_zoloftbusted1

The legal defense by Lilly, repeated by the media and others, is that any suicides are caused by the condition, depression, not by their drug—whether the violence is associated with short-term drug use, long-term drug use, increased doses, withdrawal, or rechallenge. There is no website, as far as I know, for violent acts committed by persons who never received SSRIs, or for total violent acts; hence the denominator for violent acts is not known. Also unknown is the fraction of potentially violent persons who are treated with SSRIs, or of persons treated with SSRIs who are potentially violent. The published studies on actual suicide, however, compare patients on SSRIs with similar patients on non- SSRI antidepressants or placebo. Children diagnosed with OCD, not depression, also became suicidal on SSRIs, as did healthy volunteers.

Actual two- to threefold increases in suicide rates have been demonstrated as well as they could be. How else could such effects be demonstrated? Who would submit, and what institutional review board or human subjects committee would approve a study explicitly designed to show whether assaultive, homicidal, or other violent behavior increases in subjects prescribed the study drug?

Denial by SSRI makers of culpability for these risks continues to this day. Whether physicians’ acting on the Black Box warnings of 2004 and 2007 for all SSRIs will diminish the incidence of murders and suicides is not yet known. Following the introduction of fluoxetine in 1988, only a year passed before an early user committed multiple murders and suicide; many other examples followed. More than 200 lawsuits have been begun by users of SSRIs and victims’ families charging wrongful death or failure to warn; these have had mixed outcomes. There is now legal precedent for SSRIs as a cause of murder, and the maker of the SSRI is potentially liable for damages, according to David Healy.

Eli Lilly responded with total denial to the lawsuits claiming a link between fluoxetine and violence. Several claims were settled out of court with secret details and no admission of guilt. The Australian David Hawkins was freed from a murder charge by a finding of temporary insanity caused by using sertraline. Tim Tobin of Wyoming won $6.4 million from SmithKline Beecham when a jury found that a murder/suicide committed by Donald Schell was attributable to use of paroxetine. There are four other homicide cases in which the SSRI was deemed to have contributed, resulting in a suspended sentence in one case and an insanity verdict in another.

One case of homicide, with a guilty verdict and a life sentence, followed a judicial ruling that akathisia was associated with SSRI use, but that a causal relationship with homicide could not be argued; thus the link of an SSRI with homicide was disallowed. This was in direct conflict with the findings of the four trials cited above. The SSRI website was searched to find murders related to a specific SSRI whose perpetrators were acquitted based on temporary SSRI-induced insanity. There were two cases with sertraline, four cases with paroxetine, and four cases with fluoxetine. So a precedent has been established for legal recognition that an SSRI can be a cause for murder, and that the drug maker can be found liable for damages. The notices of suicidality for the SSRIs found in the PDR or package inserts before 2004 did not really warn of actual suicide or murder.

200 SSRI-related Lawsuits

The Black Box warning of 2004 about possible suicide in children under 18 years of age did not cover adults or murder at any age, so potential liability for the SSRI makers still exists. In 2007 the warning was extended to persons under age 25 years. David Healy was quoted as saying that the warning was overdue, and that the risk was not likely to disappear above age 25. This was shown by the trials from GlaxoSmithKline on paroxetine cited above.

Antidepressants are extraordinarily difficult to assess for risks or benefits in trials. At most, 11%–30% of patients with depression or related conditions who take SSRIs actually benefited beyond the placebo effect on normal doses. Of the perceived benefit, 32%–67% can be attributed to the placebo effect. Adverse effects, mostly dose-dependent, will appear in up to 75% of patients on normal doses. Of these, studies suggest that suicidality will be observed in an additional 2%–13% (1 in 50 to 1 in 9) of patients on normal doses, beyond what is seen on placebo or many non-SSRI antidepressant drugs. This is sufficiently frequent that a typical prescribing physician should observe examples in routine practice.

The actual suicide rate could be about 123/100,000 (1 in 813) higher in patients on SSRIs than in those on tricyclics or placebo. Studies show that many more suicides are on normal doses of SSRIs beyond what is seen on placebo or many non-SSRI antidepressant drugs. Available data suggest that actual murders may be committed at about the rate of 250/100,000 (1 in 400) SSRI-treated patients beyond what is seen on placebo or many non-SSRI antidepressantdrugs, and that many more murders will be attempted on normal doses as well. While correlation does not prove causation, and results of court trials are not medical science, the data for suicide are solid, and the association of murder with suicide is very suggestive. Now that there is a stronger Black Box warning, physicians who ignore it may be liable for damages; the warning primarily protects the manufacturers of SSRIs. There is obviously great peril in drawing conclusions about causat i on from press report s or court decisions.

While manufacturers have a vested interest in exonerating their drugs, plaintiffs have an interest in blaming it, and defendants in exonerating themselves. We need careful, independent analysis of existing study data. In addition to randomized controlled trials, evidence from basic science ( neuropharmacology) and challenge/dechallenge/rechallenge investigations needs to be sought. Both the public and individual patients are imperiled by an incorrect answer to the pressing questions about these widely prescribed drugs. Future studies may show lower levels of murder and suicide with close supervision, and with better matching of this drug type to patient type.

Conclusionsattemptedsimultaneous
Joel M. Kauffman, Ph.D.

Acknowledgements:
Joel M. Kauffman, Ph.D., professor of chemistry emeritus at the
University of the Sciences, 600 S. 43rd St., Philadelphia, PA 19104-4495,
Contact: kauffman@bee.net.

Learn More
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Frances E. H. Pane edited the manuscript. David Moncrief piqued my interest by providing a review copy of by Richard DeGrandpre.
The Cult of Pharmacology: How America Became the World’s Most Troubled Drug Culture

Journal of American Physicians and Surgeons Volume 14 Number 1 Spring 2009 11
Potential conflicts of interest: The author has neither a financial interest in any drug mentioned, nor in any alternate treatments for treating any mental illness.

REFERENCES
DeGrandpre R.,Durham, N.C.: Duke University Press; 2006.

The Cult of Pharmacology: How America Became the World’s Most Troubled Drug Culture.
Bridge JA, Iyengar S, Salary CB, et al. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment. 2007;297:1683-1696.

Jørgensen AW, Hilden J, Gøtzsche PC. Cochrane reviews compared
with industry supported meta-analyses and other meta-analyses of
the same drugs: systematic review. doi:10.1136/bmj.38973.
444699.0B (publ Oct 2006).

Cohen JS. New York, N.Y.: Tarcher/Putnam; 2001.

Mackay FJ, Dunn NR, Wilton LV, et al. A comparison of fluvoxamine, fluoxetine, sertraline and paroxetine examined by observational cohort studies. 1997;6:235-246.

Park L, Covi L. Nonblind placebo trial. 1965;336-345.

Cole JO. Therapeutic efficiency of antidepressant drugs: a review. 1964;190:124-131.

Kirsch I, Moore TJ, Scoboria A, et al. The emperor’s new drugs: an analysis of antidepressant medication data submitted to the U. S. Food and Drug Administration. 2002;5(1):23-33.

Kirsch I, Deacon BJ, Huedo-Medina TB, et al. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. 2008;5(2):e45. doi:10.1371/journal.pmed.0050045.

Healy D. One flew over the conflict of interest nest. 2007;6(1):26-27.

Healy D. New York, N.Y.: New York University Press; 2004.

Healy D. FDA Psychopharmacologic Drugs Advisory Committee hearings. Available at:: www.healyprozac.com/PDAC. Accessed May 13, 2007.

Wolfe SM, ed. SSRIs can have dangerous interactions with other drugs. 2008;14(1):2-5. www.citizen.org/hrg/. Accessed Feb 4, 2009.

JAMA BMJ, Over Dose: The Case Against the Drug Companies.
Pharmacoepidemiol Drug Safety Arch Gen Psychiatry

JAMA
Prevention & Treatment
PLoS Medicine
World Psychiatry
Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression.
Worst Pills Best Pills News

Braconnier A, Le Coent R, Cohen D. Paroxetine versus clomipramine in adolescents with severe major depression: a double-blind, randomized, multicenter trial. 2003;42:22-29.

Anderson IM, Tomenson BM. Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants: a meta-analysis. 1995;310:1433-1438.

Healy D. Lines of evidence on the risks of suicide with selective serotonin reuptake inhibitors. 2003:72:71-79.

Healy D, Herxheimer A, Menkes DB. Antidepressants and violence: problems at the interface of medicine and law.
2006;3(9):1478-1487.

Beasley CM, Dornseif BE, Bosomworth JC. Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression. 1991;303:685-692.

Cohen H. Antidepressants: clinical use and litigation. In: 2nd ed. O’Donnell JT, ed. Tucson, Ariz.: Lawyers & Judges Publ.Co; 2006:379-390.

Ross G. Black Box backfire. Apr 21, 2007.

Donovan S, Clayton A, Beeharry M, et al. Deliberate self-harm and antidepressant drugs. 2000;177:551-556.

Kai zar EE, Gr eenhouse JB, Sel t man H, Kel l eher K . Do antidepressants cause suicidality in children? A Bayesian meta-analysis. 2006;3:73-98.

Berenson ML, Levine DM.. 7th ed. Upper Saddle River, N.J.: Prentilee-Hall; 1998:213-217.

Healy D, Whitaker C. Antidepressants and suicide: risk-benefit conundrums. 2003;28:331-337.

Fergusson D, Doucette S, Glass KC, et al. Association between suicide attempts and selective serotonin reuptake inhibitors.2005;330:396-402.

Donovan S, Kelleher MJ, Lambourn J, Foster T. The occurrence of suicide following the prescription of antidepressant drugs.1999;5:181-192.

Jick SS, Dean AD, Jick H. Antidepressants and suicide.1995;310:215-218.

Wessely S, Kerwin R. Suicide risk and SSRIs. 2004;292:379-381.

Jick H, Kaye JA, Jick SS. Antidepressants and the risk of suicidal behaviors. 2004;292:338-343.

Carey B. FDA expands suicide warning on drugs. ,May 3, 2007:A17.

J Am Acad Child Psychiatry BMJPsychother PsychosomPLoS Med
BMJ

Drug Injury:Liability, Analysis and Prevention.

Wall Street Journal,Br J Psychiatry Clinical Trials

Basic Business Statistics: Concepts and Applications J Psychiatry Neuroscience

New York Times:Journal of American Physicians and Surgeons Volume 14 Number 1 Spring 2009

USA Trade Name Generic Name:
SSRIs
Celexa
Luvox
Paxil
Prozac
Zoloft
non-SSRIs
Effexor
Remeron
Serzone
Wellbutrin
(UK)
citalopram
fluvoxamine
paroxetine
fluoxetine
sertraline
venlafaxine
mirtazapine
nefazodone
bupropion
dothiepin USA Trade Name Generic Name
SSRIs
Celexa
Luvox
Paxil
Prozac
Zoloft
non-SSRIs
Effexor
Remeron
Serzone
Wellbutrin
(UK)
citalopram
fluvoxamine
paroxetine
fluoxetine
sertraline
venlafaxine
mirtazapine
nefazodone
bupropion
dothiepin

Physicians Desk Reference (PDR)
Joel M. Kauffman, Ph.D.
Table 1. Commonly Prescribed SSRIs and Other Antidepressants Selective Serotonin Reuptake Inhibitor (SSRI) Drugs:
More Risks Than Benefits?

Journal of American Physicians and Surgeons Volume 14 Number 1 Spring 2009 7 Physicians Desk Reference (PDR)
Joel M. Kauffman, Ph.D.
Table 1. Commonly Prescribed SSRIs and Other Antidepressants Selective Serotonin Reuptake Inhibitor (SSRI) Drugs:
More Risks Than Benefits?

Journal of American Physicians and Surgeons Volume 14 Number 1 Spring 2009 7

JAMAwhole12,69210,98313,74112,73450,15013,554

10 dead, 7 wounded: dosage increased one week before rampage
15 year old shoots two teachers, killing one: then kills himself
Columbine High School: 15 dead, 24 wounded
Four dead, twenty injured after Prozac withdrawal
Teen shoots at two students: kills his father
Jury finds Paxil was cause of murder-suicide
Man cleared of charges due to Paxil withdrawal defense
Not guilty by reason of Prozac induced insanity: mother kills daughter
Nine dead, 12 wounded in workplace shooting
11 year old hangs himself: lawsuit

Journal of American Physicians and Surgeons Volume 14 Number 1 Spring 2009

3,174 total views, 5 views today

DEPRESSION MED: Woman Stabs To Death A Man On A Stairwell: Australia

Paragraph three reads:  “Defence solicitor Bernie Balmer said Epshtein was on medication for anxiety, bipolar, depression, pain and one to lower her heart rate.”

http://www.theage.com.au/national/woman-in-court-over-stabbing-murder-20090803-e6l0.html

Woman in court over stabbing murder

Steve Butcher

August 3, 2009 – 12:04PM

A 21-year-old woman charged with the stabbing murder last week of a man in a St Kilda stairwell has appeared in court.

A lawyer for Natasha Epshtein told Melbourne Magistrates Court today his client had been treated by two doctors for five separate health conditions.

Defence solicitor Bernie Balmer said Epshtein was on medication for anxiety, bipolar, depression, pain and one to lower her heart rate.

Epshtein appeared before Deputy Chief Magistrate Dan Muling in a low-cut, black t-shirt with close-cropped hair and tattoos on her upper chest.

She is charged with murdering Peter James Len on July 30.

Mr Balmer said she would consent to a DNA sample being taken at a later date.

She was remanded to appear again on November 30.

525 total views, 2 views today

DEPRESSION MED: Woman Assaults a Deputy Sheriff: Colorado

Paragraqphs two and three read:  “Tanya Eliz Moschetti, 42, 1253 12 1/2 Road, was arrested on suspicion of second-degree assault on a peace officer, third-degree assault and criminal mischief after deputies received a report of a possible overdose at her house and were told she was running around the house naked and breaking things, according to an arrest affidavit.”

“When deputies arrived, they noted Moschetti, who was standing outside and cursing at a man inside, was slurring her speech and had a distant gaze in her eyes. She said she was taking medication for depression.”

http://www.gjsentinel.com/hp/content/news/police/stories/2009/08/02/080309_3a_Blotter.html

Police blotter: August 3, 2009

Sunday, August 02, 2009

Assault suspect arrested

A Loma woman was arrested Saturday after she allegedly assaulted a sheriff’s deputy who had responded to a domestic disturbance at her house, the Mesa County Sheriff’s Department said.

Tanya Eliz Moschetti, 42, 1253 12 1/2 Road, was arrested on suspicion of second-degree assault on a peace officer, third-degree assault and criminal mischief after deputies received a report of a possible overdose at her house and were told she was running around the house naked and breaking things, according to an arrest affidavit.

When deputies arrived, they noted Moschetti, who was standing outside and cursing at a man inside, was slurring her speech and had a distant gaze in her eyes. She said she was taking medication for depression.

At one point, Moschetti tried to re-enter the house and struck a deputy on the arm when he tried to stop her.

Deputies arrested Moschetti and booked her into Mesa County Jail.

523 total views, 2 views today

Antidepressant use doubles in U.S., study finds

“Not only are more U.S. residents being treated with antidepressants, but also those who are being treated are receiving more antidepressant prescriptions,” they added.
[Note by Ann Blake-Tracy: Far too many doctors are prescribing two and even three antidepressants at a time which should never be done due to the high potential of resulting Serotonin Syndrome from the combination.]
“During this period, individuals treated with antidepressants became more likely to also receive treatment with antipsychotic medications . . . “
[Note by Ann Blake-Tracy: Additional supporting data to add to the story we just sent out on 81% of those diagnosed with Bipolar Disorder having been previously treated with antidepressants or Ritalin type drugs – making these popular drugs the main triggers for Bipolar Disorder and manic psychosis.]

Antidepressant use doubles in U.S., study finds

1 in 10 are taking medication to improve mood, fewer going to talk therapy

By Maggie Fox

updated 2:44 p.m. CT, Mon., Aug 3, 2009

WASHINGTON – Use of antidepressant drugs in the United States doubled between 1996 and 2005, probably because of a mix of factors, researchers reported on Monday.

About 6 percent of people were prescribed an antidepressant in 1996 — 13 million people. This rose to more than 10 percent or 27 million people by 2005, the researchers found.

“Significant increases in antidepressant use were evident across all sociodemographic groups examined, except African Americans,” Dr. Mark Olfson of Columbia University in New York and Steven Marcus of the University of Pennsylvania in Philadelphia wrote in the Archives of General Psychiatry.

“Not only are more U.S. residents being treated with antidepressants, but also those who are being treated are receiving more antidepressant prescriptions,” they added.

More than 164 million prescriptions were written in 2008 for antidepressants, totaling $9.6 billion in U.S. sales, according to IMS Health.

Drugs that affect the brain chemical serotonin like GlaxoSmithKline’s Paxil, known generically as paroxetine, and Eli Lilly and Co’s Prozac, known generically as fluoxetine, are the most commonly prescribed class of antidepressant. But the study found the effect in all classes of the drugs.

Olfson and Marcus looked at the Medical Expenditure Panel Surveys done by the U.S. Agency for Healthcare Research and Quality, involving more than 50,000 people in 1996 and 2005.

“During this period, individuals treated with antidepressants became more likely to also receive treatment with antipsychotic medications and less likely to undergo psychotherapy,” they wrote.

Newer drugs, more social acceptance
The survey did not look at why, but the researchers made some educated guesses. It may be more socially acceptable to be diagnosed with and treated for depression, they said. The availability of new drugs may also have been a factor.

“Although there was little change in total promotional spending for antidepressants between 1999 ($0.98 billion) and 2005 ($1.02 billion), there was a marked increase in the percentage of this spending that was devoted to direct-to consumer advertising, from 3.3 percent ($32 million) to 12 percent ($122.00 million),” they added.

Dr. Eric Caine of the University of Rochester in New York said he was concerned by the findings. “Antidepressants are only moderately effective on population level,” he said in a telephone interview.

Cost may be deterrent to talk therapy
Caine, who was not involved in the research, noted that several studies show therapy is as effective as, if not more effective than, drug use alone.

“There are no data to say that the population is healthier. Indeed, the suicide rate in the middle years of life has been climbing,” he said.

Olfson and Marcus said out-of-pocket costs for psychotherapy and lower insurance coverage for such visits may have driven patients away from seeing therapists in favor of an easy-to-prescribe pill.

The rise in antidepressant prescriptions also is seen despite a series of public health warnings on use of antidepressant drugs beginning in 2003 after clinical trials showed they increased the risk of suicidal thoughts and behaviors in children and teens.

In February 2005, the U.S. Food and Drug Administration added its strongest warning, a so-called black box, on the use of all antidepressants in children and teens.

Copyright 2009 Reuters. Click for restrictions.

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SSRI Medications

Below is a the drug manufactures BEST GUESS as to how SSRI antidepressants work in your brain. They fully admit that they really don’t know how they work. However, we maintain that the positive effects that patients report come from the stimulant, amphetamine-like, nature of these mind-altering drugs.

Learn the truth about these drugs in “Prozac: Panacea or Pandora?”

What you need to know about serotonin-enhancing medications

Selective Serotonin Reuptake Inhibitors do exactly that: Inhibit the reuptake of serotonin, thus leaving excess serotonin which allows this stimulation to continue. It has long been known that inhibiting the reuptake of serotonin will produce depression, suicide, violence, psychosis, mania, cravings for alcohol and other drugs, reckless driving, etc. [See full list of reactions below]

The most popular drugs that produce this reuptake of serotonin are:

SSRI Antidepressants: Prozac, Serafem, Zoloft, Paxil, Luvox, Celexa, Lexapro

SNRI Antidepressants: Effexor, Remeron, Serzone, Cymbalta

Atypical Antipsychotics: Zyprexa, Geodon, Abilify, Seroquel, Risperdal

Weight Loss Medications: Fen-Phen, Redux, Meridia

Pain Killers: (Any opium or heroin derivative) Morphine, OxyContin, Ultram, Tramadol, Percocet, Percodan, Lortab, Demerol, Darvon or Darvocet, Codeine, Buprenex, Dilaudid, Talwin, Stadol, Vicodin, Duragesic Patches, Fentanyl Transdermal, Methadone, Dextromethorphan (commonly used in cough syrups), etc.

WARNING: Anesthetics can also fall into this group as well as drugs used for other purposes. Always check to see what the mechanism of action is in a drug before combining it with another serotonergic agent or using it soon after the use of a serotonergic agent because the combination of two can cause the potentially fatal reaction known as Serotonin Syndrome. As the main function of serotonin is constriction of smooth muscle tissue, Serotonin Syndrome produces death via multiple organ failure.

“Psychedelic agents mimic the effects of serotonin.”

The brain chemical these drugs increase, serotonin, is the same brain chemical that LSD, PCP and other psychedelic drugs mimic in order to produce their hallucinogenic effects. And remember that psychedelic agents are “a class of compounds with no demonstrated therapeutic use, a history of extensive abuse, and the ability to provoke psychosis. Yet many brain researchers value the psychedelic agents above any of the other psychoactive drugs” because “the research into psychedelic drugs has already enriched our understanding of how the brain regulates behavior.” (Dr. Solomon Snyder, DRUGS AND THE BRAIN). Just how much will these brain researchers learn from our experience with these drugs designed to specifically increase serotonin, the same brain chemical the psychedelic agents mimic to produce their effects?

We know that these drugs interfere with serotonin metabolism (demonstrated by levels of the serotonin metabolite 5HIAA). It is not serotonin that is low in these disorders, it is this by-product 5HIAA, which indicates the level of serotonin metabolism, that is low in depression, suicide, etc. Yet as serotonin (5HT) goes up serotonin metabolism (5HIAA) generally comes down. We already have studies demonstrating at what percentage each of these drugs increase 5HT and decrease 5HIAA. Here are the results of elevated levels of serotonin (5HT) and decreased levels of serotonin metabolism (5HIAA):

Elevated 5HT (serotonin) levels:

  1. schizophrenia, psychosis, mania, etc.
  2. mood disorders (depression, anxiety, etc.)
  3. organic brain disease – especially mental retardation at a greater incident rate in children
  4. autism (a self-centered or self-focused mental state with no basis in reality)
  5. Alzheimer’s disease
  6. old age
  7. anorexia
  8. constriction of the blood vessels
  9. blood clotting
  10. constriction of bronchials and other physical effects

Lower 5HIAA (serotonin metabolism) levels:

  1. suicide (especially violent suicide)
  2. arson
  3. violent crime
  4. insomnia
  5. depression
  6. alcohol abuse
  7. impulsive acts with no concern for punishment
  8. reckless driving
  9. dependence upon various substances
  10. bulimia
  11. multiple suicide attempts
  12. hostility and more contact with police
  13. exhibitionism
  14. arguments with spouses, friends and relatives
  15. obsessive compulsive behavior
  16. impaired employment due to hostility, etc.

All are exactly what patients and their families have continued to report to be their experience on these drugs since Prozac was introduced! These individuals are frantically searching for answers while this research sits right under our noses. Although this is a totally different picture than pharmaceutical marketing departments would have us believe, marketing claims and reality rarely have much in common.

Researchers tell us that five, ten or twenty years later it is not uncommon to find we have another thalidomide on our hands. Raising 5HT (serotonin) and lowering 5HIAA (serotonin metabolism) in such a high number of people can produce very serious, extensive and long term problems for all of society. Even more frightening for the future of our society is the rapidly rising and widely accepted practice of prescribing these drugs to small children and adolescents. This crucial medical research must be addressed openly, without delay, rather than remain buried in seldom read medical research documents as has been the case in the past with other mind-altering medications, once thought to be safe, which were subsequently prohibited by law.

[SOURCE: PROZAC: PANACEA OR PANDORA?, BY ANN BLAKE TRACY]

  • Adverse SSRI Reactions
  • Prozac Package Insert
  • Hyperserotonemia
  • Serotonin Syndrome

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How a New Policy Led to Seven Deadly Drugs

How a New Policy Led to Seven Deadly Drugs

http://www.latimes.com/news/nation/reports/fda/lat_fda001220.htm

By DAVID WILLMAN

WASHINGTON–For most of its history, the United States Food and Drug Administration approved new prescription medicines at a grudging pace, paying daily homage to the physician’s creed, “First, do no harm.”

Then in the early 1990s, the demand for AIDS drugs changed the political climate. Congress told the FDA to work closely with pharmaceutical firms in getting new medicines to market more swiftly. President Clinton urged FDA leaders to trust industry as “partners, not adversaries.”

The FDA achieved its new goals, but now the human cost is becoming clear.

Seven drugs approved since 1993 have been withdrawn after reports of deaths and severe side effects. A two-year Los Angeles Times investigation has found that the FDA approved each of those drugs while disregarding danger signs or blunt warnings from its own specialists. Then, after receiving reports of significant harm to patients, the agency was slow to seek withdrawals.

According to “adverse-event” reports filed with the FDA, the seven drugs were cited as suspects in 1,002 deaths. Because the deaths are reported by doctors, hospitals and others on a voluntary basis, the true number of fatalities could be far higher, according to epidemiologists.

An adverse-event report does not prove that a drug caused a death; other factors, such as preexisting disease, could play a role. But the reports are regarded by public health officials as the most reliable early warnings of danger.

The FDA’s performance was tracked through an examination of thousands of pages of government documents, other data obtained under the Freedom of Information Act and interviews with more than 60 present and former agency officials.

The seven drugs were not needed to save lives. One was for heartburn. Another was a diet pill. A third was a painkiller. All told, six of the medicines were never proved to offer lifesaving benefits, and the seventh, an antibiotic, was ultimately judged unnecessary because other, safer antibiotics were available.

The seven are among hundreds of new drugs approved since 1993, a period during which the FDA has become known more for its speed than its caution. In 1988, only 4% of new drugs introduced into the world market were approved first by the FDA. In 1998, the FDA’s first-in-the-world approvals spiked to 66%.

The drug companies’ batting average in getting new drugs approved also climbed. By the end of the 1990s, the FDA was approving more than 80% of the industry’s applications for new products, compared with about 60% at the beginning of the decade.

And the companies have prospered: The seven unsuccessful drugs alone generated U.S. sales exceeding $5 billion before they were withdrawn.

Once the world’s unrivaled safety leader, the FDA was the last to withdraw several new drugs in the late 1990s that were banned by health authorities in Europe.

“This track record is totally unacceptable,” said Dr. Curt D. Furberg, a professor of public health sciences at Wake Forest University. “The patients are the ones paying the price. They’re the ones developing all the side effects, fatal and non-fatal. Someone has to speak up for them.”

The FDA’s faster and more lenient approach helped supply pharmacy shelves with scores of new remedies. But it has also yielded these fatal missteps, according to the documents and interviews:

1. Only 10 months ago, FDA administrators dismissed one of its medical officer’s emphatic warnings and approved Lotronex, a drug for treating irritable bowel syndrome. Lotronex has been linked to five deaths, the removal of a patient’s colon and other bowel surgeries. It was pulled off the market on Nov. 28.

2. The diet pill Redux, approved in April 1996 despite an advisory committee’s vote against it, was withdrawn in September 1997 after heart-valve damage was detected in patients put on the drug. The FDA later received reports identifying Redux as a suspect in 123 deaths.

3. The antibiotic Raxar was approved in November 1997 in the face of evidence that it may have caused several fatal heart-rhythm disruptions in clinical studies. FDA officials chose to exclude any mention of the deaths from the drug’s label. The maker of the pill withdrew it in October 1999. Raxar was cited as a suspect in the deaths of 13 patients.

4. The blood pressure medication Posicor was approved in June 1997 despite findings by FDA specialists that it might fatally disrupt heart rhythm and interact with certain other drugs, posing potentially severe risk. Posicor was withdrawn one year later; reports cited it as a suspect in 100 deaths.

5. The painkiller Duract was approved in July 1997 after FDA medical officers warned repeatedly of the drug’s liver toxicity. Senior officials sided with the manufacturer in softening the label’s warning of the liver threat. The drug was withdrawn 11 months later. By late 1998, the FDA had received voluntary reports citing Duract as a suspect in 68 deaths, including 17 that involved liver failure.

6. The diabetes drug Rezulin was approved in January 1997 over a medical officer’s detailed opposition and was withdrawn this March after the agency had linked 91 liver failures to the pill. Reports cite Rezulin as a suspect in 391 deaths.

7. The nighttime heartburn drug Propulsid was approved in 1993 despite evidence that it caused heart-rhythm disorders. The officials who approved the drug failed to consult the agency’s own cardiac specialists about the signs of danger. The drug was taken out of pharmacies in July after scores of confirmed heart-rhythm deaths. Overall, Propulsid has been cited as a suspect in 302 deaths.

The FDA’s handling of Propulsid put children at risk.

The agency never warned doctors not to administer the drug to infants or other children even though eight youngsters given Propulsid in clinical studies had died. Pediatricians prescribed it widely for infants afflicted with gastric reflux, a common digestive disorder.

Parents and their doctors had no way of knowing that the FDA, in August 1996, had found Propulsid to be “not approvable” for children.

“We never knew that,” said Jeffrey A. Englebrick, a heavy-equipment welder in Shawnee, Kan., whose 3-month-old son, Scott, died on Oct. 28, 1997, after taking Propulsid. “To me, that means they took my kid as a guinea pig to see if it would work.”

By the time the drug was pulled, the FDA had received reports of 24 deaths of children under age 6 who were given Propulsid. By then the drug had generated U.S. sales of $2.5 billion for Johnson & Johnson Co.

Questions also surround the recent approvals of other compounds that remain on the market, including a new flu drug called Relenza. In February of 1999, an FDA advisory committee concluded that Relenza had not been proved safe and effective. The agency nevertheless approved it. Following the deaths of seven patients, the FDA in January issued a “public health advisory” to doctors.

A ‘Lost Compass’
A total of 10 drugs have been pulled from the market in just the past three years for safety reasons, including three pills that were approved before the shift that took hold in 1993. Never before has the FDA overseen the withdrawals of so many drugs in such a short time. More than 22 million Americans–about 10% of the nation’s adult population–took those drugs.

With many of the drugs, the FDA used tiny-print warnings or recommendations in package labeling as a way to justify approvals or stave off withdrawals. In other instances, the agency has withheld safety information from labels that physicians say would call into question the use of the product.

Present and former FDA specialists said the regulatory decisions of senior officials have clashed with the agency’s central obligation, under law, to “protect the public health by ensuring . . . that drugs are safe and effective.”

“They’ve lost their compass and they forget who it is that they are ultimately serving,” said Dr. Lemuel A. Moye, a University of Texas School of Public Health physician who served from 1995 to 1999 on an FDA advisory committee. “Unfortunately the public pays for this, because the public believes that the FDA is watching the door, that they are the sentry.”

The FDA’s shift is felt directly in the private practice of medicine, said Dr. William L. Isley, a Kansas City, Mo., diabetes specialist. He implored the agency to reassess Rezulin three years ago after a patient he treated suffered liver failure taking the pill.

“FDA used to serve a purpose,” Isley said. “A doctor could feel sure that a drug he was prescribing was as safe as possible. Now you wonder what kind of evaluation has been done, and what’s been swept under the rug.”

FDA officials said that they have tried conscientiously to weigh benefits versus risks in deciding whether to approve new drugs. They noted that many doctors and patients complain when a drug is withdrawn. “All drugs have risks; most of them have serious risks,” said Dr. Janet Woodcock, director of the FDA’s drug review center. She added that some of the withdrawn drugs were “very valuable, even if not lifesaving, and their removal from the market represents a loss, even if a necessary one.” Once a drug is proved effective and safe, Woodcock said, the FDA depends on doctors “to take into account the risks, to read the label. . . . We have to rely on the practitioner community to be the learned intermediary. That’s why drugs are prescription drugs.”

In a May 12, 1999, article co-authored with FDA colleagues and published by the Journal of the American Medical Assn., Woodcock said, “The FDA and the community are willing to take greater safety risks due to the serious nature of the [illnesses] being treated.”

Compared to the volume of new drugs approved, they wrote, the number of recent withdrawals “is particularly reassuring.”

However, agency specialists point out that both approvals and withdrawals are controlled by Woodcock and her administrators. When they consider a withdrawal, they face the unpleasant prospect of repudiating their original decision to approve.

Woodcock, 52, received her medical degree at Northwestern University and is a board-certified internist. She alluded in a recent interview to the difficulty she feels in rejecting a proposed drug that might cost a company $150 million or more to develop. She also acknowledged the commercial pressures in a March 1997 article.

“Consumer protection advocates want to have drugs worked up well and thoroughly evaluated for safety and efficacy before getting on the market,” Woodcock wrote in the Food and Drug Law Journal. “On the other hand, there are economic pressures to get drugs on the market as soon as possible, and these are highly valid.”

But this summer–following the eighth and ninth drug withdrawals–Woodcock said the FDA cannot rely on labeling precautions, alone, to resolve safety concerns.

“As medical practice has changed . . . it’s just much more difficult for [doctors] to manage” the expanded drug supply, Woodcock said in an interview. “They rely upon us much more to make sure the drugs are safe.”

Another FDA administrator, Dr. Florence Houn, voiced similar concern in remarks six months ago to industry officials: “I think the lessons learned from the drug withdrawals make us leery.”

Yet the imperative to move swiftly, cooperatively, remains.

“We are now making decisions more quickly and more predictably while maintaining the same high standards for product safety and efficacy,” FDA Commissioner Jane E. Henney said in a National Press Club speech on Dec. 12.

Motivated by AIDS
The impetus for change at the FDA emerged in 1988, when AIDS activists paralyzed operations for a day at the agency’s 18-story headquarters in Rockville, Md. They demanded immediate approval of experimental drugs that offered at least a ray of hope to those otherwise facing death.

The FDA often was taking more than two years to review new drug applications. The pharmaceutical industry saw a chance to loosen the regulatory brakes and expedite an array of new products to market. The companies and their Capitol Hill lobbyists pressed for advantage: If unshackled, they said, the companies could invent and develop more remedies faster.

The political pressure mounted, and the FDA began to bow. By 1991, agency officials told Congress they were making significant progress in speeding the approval process.

The emboldened companies pushed for more. They proposed that drugs intended for either life-threatening or “serious” disorders receive a quicker review.

“The pharmaceutical companies came back and lobbied the agency and the Hill for that word, ‘serious,’ ” recalled Jeffrey A. Nesbit, who in 1991 was chief of staff to FDA Commissioner David A. Kessler. “Their argument was, ‘Well, OK, there’s AIDS and cancer. But there are drugs [being developed] for Alzheimer’s. And that’s a serious illness.’ They started naming other diseases. They began to push that envelope.”

The wielding of this single, flexible adjective–“serious”–swung wide the regulatory door knocked ajar by the AIDS crisis.

New Order Takes Hold
In 1992, Kessler issued regulations giving the FDA discretion to “accelerate approval of certain new drugs” for serious or life-threatening conditions. That same year a Democrat-controlled Congress approved and President Bush signed the Prescription Drug User Fee Act. It established goals that call for the FDA to review drugs within six months or a year; the pharmaceutical companies pay a user fee to the FDA, now $309,647, with the filing of each new drug application.

The newly elected Clinton administration climbed aboard with its “reinventing government” project. Headed by Vice President Al Gore, the project called for the FDA, by January 2000, to reduce “by an average of one year the time required to bring important new drugs to the American public.” As Clinton put it in a speech on March 16, 1995, the objective was to “get rid of yesterday’s government.”

For the FDA’s medical reviewers–the physicians, pharmacologists, chemists and biostatisticians who scrutinize the safety and effectiveness of emerging drugs–a new order had taken hold.

The reviewers work out of public view in secure office buildings clustered along Maryland’s Route 355. At the jet-black headquarters building, the decor is institutional, the corridors and third-floor cafeteria without windows. The reviewers examine truckloads of scientific documents. They are well-educated; some are highly motivated to do their best for a nation of patients who unknowingly count on their expertise.

One of these reviewers was Michael Elashoff, a biostatistician who arrived at the FDA in 1995 after earning degrees from UC Berkeley and the Harvard School of Public Health.
“From the first drug I reviewed, I really got the sense that I was doing something worthwhile. I saw what a difference a single reviewer can make,” said Elashoff, the son and grandson of statisticians.

Last year he was assigned to review Relenza, the new flu drug developed by Glaxo Wellcome. He recommended against approval.

“The drug has no proven efficacy for the treatment of influenza in the U.S. population, no proven effect on reducing person-to-person transmissibility, and no proven impact on preventing influenza,” Elashoff wrote, adding that many patients would be exposed to risks “while deriving no benefit.”

An agency advisory committee agreed and on Feb. 24 voted 13 to 4 against approving Relenza. After the vote, senior FDA officials upbraided Elashoff. They stripped him of his review of another flu drug. They told him he would no longer make presentations to the advisory committee. And they approved Relenza as a safe and effective flu drug.

Lost Faith in the System
Elashoff and other FDA reviewers discern a powerful message.
“People are aware that turning something down is going to cause problems with [officials] higher up in FDA, maybe more problems than it’s worth,” he said. “Before I came to the FDA I guess I always assumed things were done properly. I’ve lost a lot of faith in taking a prescription medicine.”

Elashoff left the FDA four months ago.

“Either you play games or you’re going to be put off limits . . . a pariah,” said Dr. John L. Gueriguian, a 19-year FDA medical officer who opposed the approval of Rezulin, the ill-fated diabetes drug. “The people in charge don’t say, ‘Should we approve this drug?’ They say, ‘Hey, how can we get this drug approved?’ ”

Said Dr. Rudolph M. Widmark, who retired in 1997 after 11 years as a medical officer: “If you raise concern about a drug, it triggers a whole internal process that is difficult and painful. You have to defend why you are holding up the drug to your bosses. . . . You cannot imagine how much pressure is put on the reviewers.”

The pressure is such that when a union representative negotiated a new employment contract for the reviewers last year, one of his top priorities was to defend what he called the “scientific integrity” of their work.

“People feel swamped. People are pressured to go along with what the agency wants,” said Dr. Robert S.K. Young, an FDA medical officer who in 1998 formed a union chapter to represent the reviewers. “You’re paying for these highly educated, trained people, and they’re not being allowed to do their job.”

Each new drug application is accompanied by voluminous medical data, enough at times to fill 1,000 or more phone books. The reviewers must master this material in less than six months or a year, while juggling other tasks.

“The devil is in the details, and detail is something we no longer have the time to go into,” said Gurston D. Turner, a veteran pharmacologist with the FDA’s scientific investigations division who retired this year. “If you know you must have your report done by a certain date, you get something done. That’s what they [top FDA officials] count, that’s all they count. And that is really, to me, a worrisome thing.”
The FDA did spur reviewers to move at record speed.

In 1994, the FDA’s goal was to finish 55% of its new drug reviews on time; the agency achieved 95%. In 1995, the goal was 70%; the FDA achieved 98%. In 1996, the goal was 80%; the FDA achieved 100%. In both 1997 and 1998, the goal was 90% and the FDA achieved 100%.

From 1993 to 1999 the agency approved 232 drugs regarded as “new molecular entities,” compared with 163 during the previous seven years, a 42% increase.

The time-limit goals quickly were treated as deadlines within the FDA–imposing relentless pressure on reviewers and their bosses to quickly conclude their work and approve the drugs.

“The goals were to be taken seriously. I don’t think anybody expected the agency to make them all,” said William B. Schultz, a deputy FDA commissioner from 1995 to 1999.

Schultz, who helped craft the 1992 user-fee act as a congressional staff lawyer, added: “You can meet the goal by either approving the drug or denying the approval. But there are some who argue that what Congress really wanted was not just decisions, but approvals. That is what really gets dangerous.”

Indeed, the FDA drug center’s 1999 annual report referred to the review goals as “the law’s deadlines.” And, Dr. Woodcock, the center director, elaborated in a subsequent agency newsletter:

“In exchange [for the user fees], FDA makes a commitment to meet certain goals for review times. [The agency] has exceeded almost all of the goals, and it expects to continue to exceed them. Basically, the number of new approved drugs has doubled, and the review times have been cut in half.”

The user fees have enabled the FDA to hire more medical reviewers. Last year, 236 medical officers examined new drugs compared with 162 officers on duty in 1992, the year before the user fees took effect.

Even so, Woodcock acknowledged in an FDA publication this fall that the workloads and tight performance goals “create a sweatshop environment that’s causing high staffing turnover.”

An FDA progress report in 1998, describing the work of agency chemists, said that “too many reviews are coming ‘down to the wire’ against the goal date. . . . This suggests a system in stress.”

Said Nesbit, the former aide to Commissioner Kessler: “The clock is always running, whereas before the clock was never running. And that changes people’s behavior.”

Dozens of officials interviewed by The Times made similar observations.

“The pressure to meet deadlines is enormous,” said Dr. Solomon Sobel, 65, director of the FDA’s metabolic and endocrine drugs division throughout the 1990s. And the pressure is not merely to complete the reviews, he said. “The basic message is to approve.”

Over the last seven years, “there has been a huge shift,” said Kathleen Holcombe, a former FDA legislative affairs staffer and congressional aide who now is a drug industry consultant. “FDA, historically, had an approach of, ‘Regulate, be tough, enforce the law [and] don’t let one thing go wrong,’ ” Holcombe said, adding that now, “the FDA sees itself much more in a cooperative role.”

How Deaths Were Calculated
Reports of adverse drug reactions to the Food and Drug Administration are considered by public health officials to be the most reliable early warnings of a product’s danger. The reports are filed to the FDA by health professionals, consumers and drug manufacturers. The Los Angeles Times inspected all reports filed in connection with seven drugs that were approved and withdrawn since 1993. By hand and by computer, The Times counted 1,002 deaths in which the filer identified the drug as the leading suspect. Since fall 1997, this top category has been termed “primary suspect.” The Times did not count any death in which the drug was identified as the “secondary suspect” or less. The methodology and results were reviewed by Sheila R. Weiss, a former FDA epidemiologist who is an assistant professor at the University of Maryland’s department of pharmacy practice and sciences.

The perception of coziness with drug makers is perpetuated by potential conflicts of interest within the FDA’s 18 advisory committees, the influential panels that recommend which drugs deserve approval or should remain on the market. The FDA allows some appointees to double as consultants or researchers for the same companies whose products they are evaluating on the public’s behalf. Such was the case during committee appraisals of several of the recently withdrawn drugs, including Lotronex and Posicor, The Times found.

Few doubt the $100-billion pharmaceutical industry’s clout. Over the last decade, the drug companies have steered $44 million in contributions to the major political parties and to candidates for the White House and both houses of Congress.

The FDA reviewers said they and their bosses fear that unless the new drugs are approved, companies will erupt and Congress will retaliate by refusing to renew the user fees. This would cripple FDA operations–and jeopardize jobs.

The companies’ money now covers about 50% of the FDA’s costs for reviewing proposed drugs–and agency officials say that persuading Congress to renew the user fees into 2007 is now a top priority.

Yet even if the user fees remain, the FDA is prohibited from spending the revenue for anything other than reviewing new drugs. So while the budget for pre-approval reviews has soared, the agency has gotten no similar increase of resources to evaluate the safety of the drugs after they are prescribed.

“It’s shocking,” said Dr. Brian L. Strom, chairman of epidemiology at the University of Pennsylvania. “How can you say, ‘Release drugs to the market sooner,’ and not know if they’re killing people? . . . It really is a dramatic statement of public priorities.”

More than 250,000 side effects linked to prescription drugs, including injuries and deaths, are reported each year. And those “adverse-event” reports by doctors and others are only filed voluntarily. Experts, including Strom, believe the reports represent as few as 1% to 10% of all such events. “There’s no incentive at all for a physician to report [an adverse drug reaction],” said Strom, who has documented the phenomenon. “The underreporting is vast.”

Even when deaths are reported, records and interviews show that companies consistently dispute that their product has caused a given death by pointing to other factors, including preexisting disease or use of another medicine.

To be sure, a chain of events affects the safe use of a prescription drug: The companies’ conduct of clinical studies; the FDA’s regulatory actions; the doctor’s decision to prescribe; the pharmacist’s filling of a handwritten prescription; the patient’s ability to take the drug as directed. A lapse at any link could prove fatal.

And once a pill is approved by the FDA, the manufacturer often spends heavily on promotion to seize the largest possible market share. This can exacerbate the risk to public health, according to experts.

“Aggressive promotion increases exposure–and doesn’t give you the time to find the problem before patients get hurt,” said Dr. Raymond L. Woosley, pharmacology department chairman at Georgetown University and a former FDA advisory committee member.

When serious side effects emerge, the FDA officials have championed using package labeling as a way to, in their words, “manage” risks. Yet the agency typically has no way to know if the labeling precautions–dense, lengthy and in tiny print–are read or followed by doctors and their patients.

The FDA often addresses unresolved safety questions by asking companies to conduct studies after the product is approved. But the research frequently is not performed–prompting the inspector general of the Department of Health and Human Services to say in 1996 that “FDA can move to withdraw drugs from the market if the post-marketing studies are not completed with due diligence.”

Since that report was issued, the FDA has not withdrawn any drug due to a company’s failure to complete a post-approval safety study. Officials conceded this week that they still do not know how often the studies are performed.

One consequence is that greater risk is shifted to doctors and patients.

For example, Woodcock and her senior aides allowed Rezulin to remain on the U.S. market nearly 2 years after it was withdrawn in Britain in December 1997. The FDA recommended frequent laboratory testing of patients using the drug but had no scientific assurance that the tests would prevent Rezulin-induced liver failure.

“They kept increasing the number of liver-function tests you should have,” noted Dr. Alastair J.J. Wood, a former FDA advisory committee member who is a professor of medicine at Vanderbilt University. “That was clearly designed to protect the FDA, to protect the manufacturer, and to dump the responsibility on the patient and the physician. If the patient developed liver disease and he hadn’t had his [tests] done, somebody was to blame and it wasn’t the manufacturer and it wasn’t the FDA.”

Industry Assurances
Leading industry officials say Americans have nothing to fear from the wave of drug approvals.

“Do unsafe drugs enter and remain in the marketplace? Absolutely not,” said Dr. Bert A. Spilker, senior vice president for scientific and regulatory affairs for the Pharmaceutical Research and Manufacturers of America, in remarks last year to industry and FDA scientists.

But during interviews over the last two years, current and former FDA specialists cited repeated instances when drugs were approved with less than compelling evidence of safety or effectiveness. They also said that important information has been excluded from the labels on some medications.

Elashoff, for instance, was surprised at the labeling for a drug called Prograf, approved in 1997 to prevent rejection of transplanted kidneys. The drug first had been approved in 1994 for use among liver-transplant patients.

The new label notes that Prograf was proved effective in a study of 412 U.S. kidney transplant patients. But no mention is made of the company’s 448-patient European study, in which 7% of the patients who took Prograf died–double the 3.5% death rate among those who received a different anti-rejection drug, documents show.

Contributors to this Report
Design director: Joe Hutchinson
Photographer: Brian Walski
Photo editor: Steve Stroud
Graphics: Rebecca Perry
Graphics editor: Chris Erskine
Researchers: Janet Lundblad, Sunny Kaplan
Editors: Roger Smith, Nan Williams, Steve Devol, Bobbi Olson, Kathie Bozanich
Web site Editors: Sarah D. Wright, Clare Sup

An auditor from the FDA’s scientific investigations unit, Antoine El-Hage, examined the European study results and concluded the “data are reliable.” Elashoff agreed in his review.
Yet the only way for doctors or patients to find that data is to search the medical literature or seek the FDA’s review documents.

Excluding the European study from the Prograf label, Elashoff said, “was just a total whitewash. . . . I think any rational person would reconsider taking this drug if they knew what happened in Europe.”

A spokesman for the manufacturer of Prograf said the company had no objection to including the European study results in the labeling. William E. Fitzsimmons, a vice president of drug development for Fujisawa Healthcare Inc., said the decision to exclude the results was entirely the FDA’s.

“We submitted that data,” he said. “It came down to what the FDA was comfortable putting in the label. We certainly have no interest in trying to hide that information. We presented it at major meetings on transplantation. . . . We’re comfortable with that information being out in the public domain.”

But if the FDA had included the European results in the label, it would have impugned the agency’s basis for approving the new, expanded use for Prograf, according to Elashoff and others.

Asked why the agency excluded the information, Woodcock said the European results were “unreliable and could be potentially misleading to doctors and patients in the U.S. if these were included in the label.”

Copyright 2000 Los Angeles Times

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ICFDA Warning on Drug Discontinuation

Taper off very, very, very slowly!!!!!!!!!!!!!!

Dropping “cold turkey” off any medication, most especially mind altering medications, can often be MORE DANGEROUS than staying on the drugs. With antidepressants the FDA has now warned that any abrupt change in dose, whether increasing or decreasing the dose, can produce suicide, hostility, or psychosis – generally a manic psychosis when you then get your diagnosis for Bipolar Disorder. Of course drug-induced Bipolar is temporary so you need to learn more about that if it has already happened to you. We have a DVD on explaining this and how to recover from it: “Bipolar? Are You Really Bipolar or Misdiagnosed Due to the Use of or Abrupt Discontinuation of an Antidepressant”: https://store.drugawareness.org/product/bipolar-disorder-streaming/

The most dangerous and yet the most common mistake someone coming off any antidepressant, atypical antipsychotic, or benzodiazaphine makes is coming off these drugs too rapidly. Tapering off VERY, VERY, VERY SLOWLY–OVER MONTHS OR YEARS (The general rule of thumb for those on antidepressants (ANY antidepressant, not just the current antidepressant – add up all time on any of them) for less than a year is to take half the amount of time on them to wean off and for long-term users for each 5 years on psychiatric drugs of any kind  the general rule of thumb is at least a year or more.), NOT JUST WEEKS OR MONTHS!—has proven the safest and most effective method of withdrawal from these types of medications. Thus the body is given the time it needs to readjust its own chemical levels. Patients must be warned to come very slowly off these drugs by shaving minuscule amounts off their pills each day, as opposed to cutting them.

WARNING: The practice of taking a pill every other day throws you into withdrawal every other day and can be very dangerous when you consider the FDA warnings on abrupt changes in dose.

This cannot be stressed strongly enough! This information on EXTREMELY gradual withdrawal is the most critical piece of information that someone facing withdrawal from these drugs needs to have.

A REMINDER: IT IS EASIER TO GET DOWN OFF A MOUNTAINTOP ONE GUARDED STEP AT A TIME THAN TO JUMP FROM THE TOP TO THE BOTTOM.

No matter how few or how many side effects you have had on these antidepressants, withdrawal is a whole new world. The worst part of rapid withdrawal can be delayed for several months AFTER you quit. So even if you think you are doing okay you quickly find that it becomes much worse. If you do not come off correctly and rebuild your body as you do, you risk:

  • Creating bouts of overwhelming depression
  • Producing a MUCH longer withdrawal and recovery period than if you had come off slowly
  • Overwhelming fatigue causing you to be unable to continue daily tasks or costing your job
  • Having a psychotic break brought on by the terrible insomnia from the rapid withdrawal, and then being locked in a psychiatric ward and being told you are either schizophrenic or most likely that you are Bipolar.
  • Ending up going back on the drugs (each period on the drugs tends to be more dangerous and problematic than the previous time you were on the drugs) and having more drugs added to calm the withdrawal effects
  • Seizures and other life threatening physical reactions
  • Violent outbursts or rages
  • REM Sleep Behavior Disorder which has always been known as a drug withdrawal state and is known to include both suicide and homicide – both committed in a sleep state.

Although my book, Prozac: Panacea or Pandora? Our Serotonin Nightmare!, contains massive amounts of information you can find nowhere else on these drugs, it does not have the extensive amount of information contained in the CD focusing mainly on withdrawal issues. The CD contains newer and updated information on safe withdrawal from these drugs. It details over an hour and a half the safest ways found over the past 30 years to withdraw from antidepressants and the drugs so often prescribed with them – the atypical antipsychotics and benzodiazapenes. And it explains why it is safest to withdraw tiny amounts from all of the medications at the same time rather than withdrawing only one at a time.

It also lists many safe alternative treatments that can assist you in getting though the withdrawal and lists other alternatives to avoid which are not safe after using antidepressants. And it contains information on how to rebuild your health after you have had it destroyed by these drugs so that you never end up feeling a need to be on these drugs again.

The CD is very inexpensive and will save you thousands in medical bills which far too many end up spending trying to do it on your own without this information. (One woman who decided she was okay coming down twice as fast as recommended paid a terrible price. After withdrawing she suffered the REM Sleep Disorder early one morning and attacked her husband with a baseball bat (for which she has no memory) and which ended their lifelong courtship and marriage. And cost her $30,000 to be in a psychiatric facility where they put her on five more drugs plus the antidepressant she had just withdrawn from! You can see why many have lamented that they wished they would have had the information on this CD before attempting withdrawal.

To order Ann Blake-Tracy’s book go to: https://store.drugawareness.org/product/prozac-panacea-or-pandora-our-serotonin-nightmare-2014-ebook-download/

To order the CD, “Help! I Can’t Get Off My Antidepressant!” go to: http://store.drugawareness.org/product/help-i-cant-get-off-my-antidepressant-mp3-download/

This is a CD doctors can also benefit from when attempting to withdraw their patients from these drugs which the World Health Organization has now told us are addictive and produce withdrawal. And doctors have begun to recommend the CD to their patients.

The Aftermath of Antidepressants

In 2005 the FDA issued strong warnings about changes in dose for antidepressants. They warned that ANY abrupt change in dose of an antidepressant, whether increasing or decreasing the dose….so that would include switching antidepressants, starting or stopping antidepressants, forgetting to take a pill, skipping doses, taking a pill one day & not the next, etc…. can cause suicide, hostility, and/or psychosis – generally a manic psychosis which is why so many are given a diagnosis for Bipolar Disorder after this withdrawal reaction that can so severely impair sleep leading to a psychotic break.

Clearly coming down too rapidly can be very, very dangerous. We encourage you to arm yourself with knowledge by downloading our CD on safe withdrawal.

http://www.drugawareness.org/wp-content/uploads/wpsc/product_images/thumbnails/helpicant.jpgclick here. order a CD download.

WARNING: In sharing this information about adverse reactions to antidepressants I always recommend that you also give reference to my CD on safe withdrawal, Help! I Can’t Get Off My Antidepressant!, so that we do not have more people dropping off these drugs too quickly – a move which I have warned from the beginning can be even more dangerous than staying on the drugs!

The FDA also now warns that any abrupt change in dose of an antidepressant can produce suicide, hostility or psychosis. And these reactions can either come on very rapidly or even be delayed for months depending upon the adverse effects upon sleep patterns when the withdrawal is rapid! You can find the CD on safe and effective withdrawal helps here: http://store.drugawareness.org/

Ann Blake Tracy, Executive Director,
International Coalition for Drug Awareness
www.drugawareness.org & http://ssristories.drugawareness.org
Author: ”Prozac: Panacea or Pandora? – Our Serotonin Nightmare – The Complete Truth of the Full Impact of Antidepressants Upon Us & Our World” & Withdrawal CD “Help! I Can’t Get Off My Antidepressant!”

 

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