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Psychiatric Drugs |
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Prozac fails
PROZAC NO BETTER THAN PLACEBO at guardian.co.uk at http://www.guardian.co.uk/society/2008/feb/26/mentalhealth.medicalresearch?gusrc=rss&feed=networkfront Sarah Boseley, Health Editor, The Guardian, February 26, 2008 Prozac, used by 40 million people, does not work say scientists: Analysis of unseen trials and other data
concludes it is no better than placebo Prozac, the bestselling antidepressant taken by 40 million people worldwide,
does not work and nor do similar drugs in the same class, according to a major review released today. The study examined all available data on the drugs, including results from clinical
trials that the manufacturers chose not to publish at the time. The trials compared the effect on patients taking the drugs
with those given a placebo or sugar pill. When all the data was pulled together, it appeared that patients had
improved - but those on placebo improved just as much as those on the drugs. The only exception is in the most severely depressed patients, according to
the authors - Prof Irving Kirsch from the department of psychology at Hull University and colleagues in the US and Canada.
But that is probably because the placebo stopped working so well, they say, rather than the drugs having worked better. "Given these results, there seems little reason to prescribe antidepressant
medication to any but the most severely depressed patients, unless alternative treatments have failed," says Kirsch. "This
study raises serious issues that need to be addressed surrounding drug licensing and how drug trial data is reported." The paper, published today in the journal PLoS (Public Library of Science) Medicine,
is likely to have a significant impact on the prescribing of the drugs. The National Institute for Health and Clinical Excellence
(Nice) already recommends that counselling should be tried before doctors prescribe antidepressants. Kirsch, who was one of
the consultants for the guidelines, says the new analysis "would suggest that the prescription of antidepressant medications
might be restricted even more". The review breaks new ground because Kirsch and his colleagues have obtained
for the first time what they believe is a full set of trial data for four antidepressants. They requested the full data under freedom of information rules from the Food
and Drug Administration, which licenses medicines in the US and requires all data when it makes a decision. The pattern they saw from the trial results of fluoxetine (Prozac), paroxetine
(Seroxat), venlafaxine (Effexor) and nefazodone (Serzone) was consistent. "Using complete data sets (including unpublished
data) and a substantially larger data set of this type than has been previously reported, we find the overall effect of new-generation
antidepressant medication is below recommended criteria for clinical significance," they write. Two more frequently prescribed antidepressants were omitted from the study because
scientists were unable to obtain all the data. Concerns have been raised in recent years about the side-effects of this class
of antidepressant. Evidence that they could prompt some young people to consider suicide led to a warning to doctors not to
prescribe them for the under-18s - with the exception of Prozac, which was considered more effective than the rest. In adults, however, the depression-beating benefits were thought to outweigh
the risks. Since its launch in the US in 1988, some 40 million people have taken Prozac, earning tens of billions of dollars
for the manufacturer, Eli Lilly. Although the patent lapsed in 2001, fluoxetine continues to make the company money - it is
now the active ingredient in Sarafem, a pill sold by Lilly for premenstrual syndrome. |
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Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug
Administration 1 Department of Psychology, University of Hull, Hull, United Kingdom, 2 University of Wyoming, Laramie, Wyoming, United States of America,
3 Center for Health, Intervention, and Prevention, University of
Connecticut, Storrs, Connecticut, United States of America, 4 Department of Psychology, University of Windsor, Windsor, Ontario,
Canada, 5 Institute for Safe Medication Practices, Huntingdon Valley, Pennsylvania,
United States of America Background Meta-analyses of antidepressant medications have reported
only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted
criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression
scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a
relevant dataset of published and unpublished clinical trials. Methods and Findings We obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA)
for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic
techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and
on drug–placebo difference scores. Drug–placebo differences increased as a function of initial severity, rising
from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very
severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very
severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was
curvilinear in drug groups and showed a strong, negative linear component in placebo groups. Conclusions Drug–placebo differences in antidepressant efficacy
increase as a function of baseline severity, but are relatively small even for severely depressed patients. The
relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among
very severely depressed patients, rather than to increased responsiveness to medication Background. Everyone feels miserable occasionally. But for some people—those with depression—these
sad feelings last for months or years and interfere with daily life. Depression is a serious medical illness caused by imbalances
in the brain chemicals that regulate mood. It affects one in six people at some time during their life, making them feel hopeless,
worthless, unmotivated, even suicidal. Doctors measure the severity of depression using the “Hamilton Rating Scale of
Depression” (HRSD), a 17–21 item questionnaire. The answers to each question are given a score and a total score
for the questionnaire of more than 18 indicates severe depression. Mild depression is often treated with psychotherapy or
talk therapy (for example, cognitive–behavioral therapy helps people to change negative ways of thinking and behaving).
For more severe depression, current treatment is usually a combination of psychotherapy and an antidepressant drug, which
is hypothesized to normalize the brain chemicals that affect mood. Antidepressants include “tricyclics,” “monoamine
oxidases,” and “selective serotonin reuptake inhibitors” (SSRIs). SSRIs are the newest antidepressants and
include fluoxetine, venlafaxine, nefazodone, and paroxetine. Why Was This Study Done? Although the US Food and Drug Administration (FDA), the UK National Institute for Health and Clinical
Excellence ( What Did the Researchers Do and Find? The researchers obtained data on all the clinical trials submitted to the FDA for the licensing of
fluoxetine, venlafaxine, nefazodone, and paroxetine. They then used meta-analytic techniques to investigate whether the initial
severity of depression affected the HRSD improvement scores for the drug and placebo groups in these trials. They confirmed
first that the overall effect of these new generation of antidepressants was below the recommended criteria for clinical significance.
Then they showed that there was virtually no difference in the improvement scores for drug and placebo in patients with moderate
depression and only a small and clinically insignificant difference among patients with very severe depression. The difference
in improvement between the antidepressant and placebo reached clinical significance, however, in patients with initial HRSD
scores of more than 28—that is, in the most severely depressed patients. Additional analyses indicated that the apparent
clinical effectiveness of the antidepressants among these most severely depressed patients reflected a decreased responsiveness
to placebo rather than an increased responsiveness to antidepressants. What Do These Findings Mean? These findings suggest that, compared with placebo, the new-generation antidepressants do not produce
clinically significant improvements in depression in patients who initially have moderate or even very severe depression,
but show significant effects only in the most severely depressed patients. The findings also show that the effect for these
patients seems to be due to 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, the finding
that extremely depressed patients are less responsive to placebo than less severely depressed patients but have similar responses
to antidepressants is a potentially important insight into how patients with depression respond to antidepressants and placebos
that should be investigated further. For
a fuller publication of the study http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pmed.0050045
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