Jan 2010 - Antidepressants worthless

Antidepressants Shown Worthless for Most Consumers, ending 22 years of deception

ALLIANCE FOR HUMAN RESEARCH PROTECTION

A Catalyst for Public Debate: Promoting Openness, Full Disclosure, and

Accountability

http://www.ahrp.org

FYI

The comments below expand upon an Infomail about the recently published JAMA

meta-analysis (http://www.ahrp.org/cms/content/view/658/110/)

After many years of controversy, the overwhelming evidence shows

that psychiatrists and general practitioners have been misprescribing

antidepressants to treat minor and moderate symptoms of depression for

patients for whom the drugs don't work. Such patients comprise the vast

majority for whom these drugs are prescribed-they are, thus placed at

greater risk for harmful drug side effects without any offsetting beneficial

effect.

The JAMA report is significant in that it is a patient-level meta-analysis

of 6 major studies that included a full range of patients diagnosed with

major or minor depressive disorder. The analysis examined the effects of the

selective serotonin reuptake inhibiter (SSRI), paroxetine (Paxil), and the

tricyclic antidepressant, imipramine (Tofranil), compared to an inert

placebo. The findings are consistent with earlier antidepressant efficacy

analyses (by Kirsch et al; Khan et al) confirming that antidepressant

medications (ADM) are ineffective in treating all but low-prevalence "very

severe" forms of depression, such as chronic dysthymia.

"What makes our findings surprising is the high level of depression symptom

severity that appears to be required for clinically meaningful drug/placebo

differences to emerge, particularly given the evidence that the majority of

patients receiving ADM in clinical practice present with scores below these

levels."

(http://jama.ama-assn.org/cgi/content/full/303/1/47).

Depending on data source, between 1.6 percent (US Surgeon General) and 4.01

percent (NIMH) of the US population is estimated to suffer this very serious

form of depression

(http://www.wrongdiagnosis.com/d/dysthymia/prevalence.htm#about_prevalence_a

nd_incidence). The latest report on the prevalence of depression by the

Centers for Disease Control and Prevention estimates 1 in 20 or 5 percent

had (2005-2006) had current depression at all levels of severity (mild,

moderate, severe, very severe)

(http://www.cdc.gov/nchs/data/databriefs/db07.htm).

If only 1.6 percent (US Surgeon General) of Americans have dysthymia and the

total prevalence of current depression at all levels of severity is 5

percent, one can conclude that antidepressant medication (ADM) is (at best)

more effective than placebo in treating people with very severe depression

(32 percent). Noting several subtle differences in response patterns among

earlier efficacy reports, the JAMA authors note:

"it would be premature to speculate regarding whether the increasing

superiority of ADM relative to placebo as severity increases is due to an

increasing efficacy of ADM or a declining efficacy of placebo."

For the remaining 68 percent of consumers of these drugs, ADM is no more

effective than an inert placebo.

Given the frequency of adverse side-effects of varying degrees of

severity-some life-threatening-logic tells that consumption of ADM poses far

greater risk for doing harm without any offsetting beneficial effect among

the overwhelming majority (68 percent) of people for whom they are

prescribed.

The severe adverse effects of imipramine (Tofranil) include:

severe allergic reactions (rash; hives; itching; difficulty breathing;

tightness in the chest; swelling of the mouth, face, lips, or tongue);

blurred vision or other vision changes; changes in sex drive; chest pain;

confusion; constipation; fainting; fast, slow, or irregular heartbeat;

fever; frequent or difficult urination; hallucinations; impulsive behavior

or other unusual changes in behavior; jaw, neck, or muscle spasms; mental or

mood changes (e.g., increased anxiety, mood swings, agitation, irritability,

nervousness, restlessness); panic attacks; ringing in the ears; seizures;

severe dizziness or drowsiness; sore throat; stomach pain; suicidal thinking

or behavior; swelling of the testicles; tremor; trouble sleeping; trouble

walking or keeping your balance; twitching of the face or tongue;

uncontrolled movements of arms and legs or stiffness; unusual bleeding or

bruising; worsening of depression; yellowing of the skin or eyes

(http://www.drugs.com/sfx/imipramine-side-effects.html).

The severe adverse effects of paroxetine (Paxil) include:

loss of appetite, unusual or severe mental/mood changes, increased

sweating/flushing, unusual fatigue, uncontrolled movements (tremor),

decreased interest in sex, changes in sexual ability, black stools, blurred

vision, change in amount of urine, "coffee ground" vomit, easy

bruising/bleeding, fainting, irregular heartbeat, muscle pain, trouble

swallowing, unusual swelling, seizures, tingling or numbness of the

hands/feet, obsessive suicidal thoughts, suicide attempts, violence,

painful, prolonged erection, serious allergic reaction, e.g., rash, itching,

swelling, severe dizziness, trouble breathing

(http://www.medicinenet.com/paroxetine-oral/article.htm)

VIOLENCE-directed at self or others--is a significant, life-threatening risk

linked to SSRI antidepressants.

Manufacturers regularly coded aggression and violence occurring in clinical

trials under the rubric of hostility. An analysis in PLoS Medicine, reveals

that the coding term, hostility, includes homicide, homicidal acts, and

homicidal ideation as well as aggressive events and "conduct disorders",

although no homicides were reported from these trials. GlaxoSmithKline's

Website shows that when hostile events occurring in both adult and pediatric

trials are summed, both on therapy and during the 30-day drug-free phase

after taper had finished, 60 (0.65%) of 9,219 patients overall had hostile

events. (http://www.gsk.com)

A previously court sealed 2007 report by psychiatrist Joseph Glenmullen, MD,

analyzing internal GSK documents-including memos and reports uncovered

during litigation-leaves little doubt that the company had data from

controlled clinical trials demonstrating an increased risk of suicide as

early as 1989. Indeed, GSK's data showed that the risk of suicidal behavior

in adults increased eightfold in patients prescribed Paxil.

Dr. Glenmullen's report is posted on the U.S. Senate Finance Committee

website: http://finance.senate.gov/press/Gpress/2008/prg020608b.pdf

There are 3,500 news reports of violence, murder, suicide, self-mutilation

involving SSRI antidepressants posted at: http://www.ssristories.com/

Media reports about the recent JAMA report of results from the patient-level

meta-analysis fail to indicate the clinical significance and true

implications of the study, despite the authors' forceful statement of

implications for physicians, policy makers, and consumers:

"True drug effects (an advantage of ADM over placebo) were nonexistent to

negligible among depressed patients with mild, moderate, and even severe

baseline symptoms, whereas they were large for patients with very severe

symptoms."

(http://www.nytimes.com/2010/01/06/health/views/06depress.html).

Against the blitz of pharmaceutical company advertising and the

self-interested arguments of prominent psychiatrists, the AHRP must ask what

action will the FDA take to protect the public from dangerous drugs whose

mostly illusory benefits are far outweighed by severe risks, thereby

undermining public health? Independent analyses have consistently shown

that antidepressants offer no clinical benefit for the vast majority of

people for whom they are prescribed. Evidence from manufacturers own

documents show that antidepressants pose severe risks of harm.

Why then, are federal drug regulators silent? Just as the Surgeon General of

the United States forcefully warned against the dangers of smoking, federal

drug regulators need to inform the American public about the dangers of

antidepressant medications-especially because they are overwhelmingly

misprescribed.

References:

1. Jay C. Fournier; Robert J. DeRubeis; Steven D. Hollon; et al.

Patient-Level Meta-analysis. JAMA. 2010;303(1):47-53

(doi:10.1001/jama.2009.1943)

http://jama.ama-assn.org/cgi/content/full/303/1/47

2. Irving Kirsch, Brett J. Deacon, Tania B. Huedo-Medina, Alan Scoboria,

Thomas J. Moore, Blair T. Johnson. Initial Severity and Antidepressant

Benefits: A Meta-Analysis of Data Submitted to the Food and Drug

Administration. PLoS Med. 2008; 5(2):e45.

http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0050045

3. Khan A, Leventhal RM, Khan SR, Brown WA. Severity

of depression and response to antidepressants and placebo: an analysis of

the Food and Drug Administration database. J Clin Psychopharmacol. 2002;

22(1):40-45. http://www.ncbi.nlm.nih.gov/pubmed/11799341

4. Healy D, Herxheimer A, Menkes DB (2006) Antidepressants and Violence:

Problems at the Interface of Medicine and Law. PLoS Med 3(9): e372.

http://www.plosmedicine.org/article/info:doi%2F10.1371%2Fjournal.pmed.003037

5. Joseph Glenmullen. Expert Report in the case of O'Neal v. SmithKline

Beecham d/b/a GlaxoSmithKline. Filed under seal, Nov. 14, 2007. Unsealed

January 18, 2008. http://finance.senate.gov/press/Gpress/2008/prg020608b.pdf

John H. Noble, Jr., PhD

AHRP Board member and Emeritus Professor,

State University of New York at Buffalo.

jhnoble@verizon.net

Vera Hassner Sharav

AHRP President

veracare@ahrp.org

212-595-8974

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http://www.nytimes.com/2010/01/06/health/views/06depress.html?em
Popular Drugs May Help Only Severe Depression
By BENEDICT CAREY
Published: January 5, 2010

Some widely prescribed drugs for depression provide relief in extreme cases but are no more effective than placebo pills for most patients, according to a new analysis released Tuesday.
The findings could help settle a longstanding debate about antidepressants. While the study does not imply that the drugs are worthless for anyone with moderate to serious depression — many such people do seem to benefit — it does provide one likely explanation for the sharp disagreement among experts about the drugs’ overall effectiveness.
Taken together, previous studies have painted a confusing picture. On one hand, industry-supported trials have generally found that the drugs sharply reduce symptoms. On the other, many studies that were not initially published, or were buried, showed no significant benefits compared with placebos.
The new report, appearing in The Journal of the American Medical Association, reviews data from previous trials on two types of drugs and finds that their effectiveness varies according to the severity of the depression being treated.
Previous analyses had found a similar pattern. But the new study is the first to analyze responses from hundreds of people being treated for more moderate symptoms, as are most people who seek care.
“I think the study could dampen enthusiasm for antidepressant medications a bit, and that may be a good thing,” said Dr. Erick H. Turner, a psychiatrist at Oregon Health and Science University. “People’s expectations for the drugs won’t be so high, and doctors won’t be surprised if they’re not curing every patient they see with medications.”
But Dr. Turner added, “The findings shouldn’t dampen expectations so much that people refuse to even try medication.”
A team of researchers, including psychologists who favor talk therapy and doctors who consult widely with drug makers, performed the new analysis, using government grants. The group evaluated six large drug trials, including 728 men and women, about half of them with severe depression and half with more moderate symptoms.
Three of the trials were of Paxil, from GlaxoSmithKline, a so-called S.S.R.I., and the other three were of imipramine, an older generic drug from the class known as tricyclics. The team, led by Jay C. Fournier and Robert J. DeRubeis of the University of Pennsylvania, found that compared with placebos, the drugs caused a much steeper reduction in symptoms of severe depression (cases scoring 25 or higher on a standard scale of severity, putting them in the top quarter of the sample). Patients with scores of less than 25 got little or no added benefit from the medications.
“We were able to give an overall estimate of effectiveness for the first time in this more moderate severity range, from 14 to 20 on the scale, in which there’s no question that doctors would likely consider prescribing medication,” Dr. DeRubeis said.
His co-authors included Steven D. Hollon and Dr. Richard C. Shelton of Vanderbilt University, Sona Dimidjian of the University of Colorado, Dr. Jan Fawcett of the University of New Mexico and Dr. Jay D. Amsterdam of Penn.
The effects of other popular S.S.R.I.’s like Lexapro and Prozac are not likely to be much different than those of Paxil, experts said.
Dr. DeRubeis and others said antidepressants’ inability to outperform placebos against moderate symptoms stemmed partly from the sustained attention that patients in drug trials received from top doctors — which itself can help relieve symptoms, drug or no drug. For some people, too, the drugs’ side effects may cancel any benefit.
“The message for patients with mild to moderate depression,” Dr. DeRubeis said, “is, ‘Look, medications are always an option, but there’s little evidence that they add to other efforts to shake the depression — whether it’s exercise, seeing the doctor, reading about the disorder or going for psychotherapy.’ ”