Over and over again we find that new isn’t better.  One more example:  The new generation of anti-depression medications (SSRs) fail to be more effective than a placebo--but for one small group.   This study confirms a previous study.  10 years ago I read articles that Prozac doesn't work, but the FDA and the industry work together. 

From Fiercepharma

Study: Antidepressants useless for most

February 26, 2008

http://www.fiercepharma.com/story/study-antidepressants-useless-for-most/2008-02-26?utm_medium=nl&utm_source=link

Here's a study guaranteed to put almost every drug maker on the defensive. Researchers analyzed every antidepressant study they could get their hands on--including a bunch of unpublished data obtained via the U.S. Freedom of Information Act--and concluded that, for most patients, SSRI antidepressants are no better than sugar pills. Only the most severely depressed get much real benefit from the drugs, the study found.

That's quite a conclusion, considering that antidepressants are among the world's top-selling meds, accounting for billions in revenues every year. Manufacturers rushed to defend their products, saying that regulators in many countries had reviewed the data and concluded the drugs were effective. GlaxoSmithKline, for instance, said that this new study only looked at "a small subset of the total data available."  {That is bull shit.}

But the study didn't come as a surprise to some, including one U.K. expert who's published research showing that drug companies only tend to publish data that shows their products in good light. The new paper, published today in the journal PLoS Medicine, (http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050045)  breaks new ground, according to The Guardian, because the researchers got access for the first time to an apparently full set of trial data for four antidepressants: Prozac (fluoxetine), Paxil (paroxetine), Effexor (venlafaxine), and Serzone (nefazodone). And the data said..."the overall effect of new-generation antidepressant medication is below recommended criteria for clinical significance." Ouch.

The study could have a ripple effect, affecting prescribing guidelines and even prompting questions about how drugs are approved. "This study raises serious issues that need to be addressed surrounding drug licensing and how drug trial data is reported," one of the researchers said. In other words, all trial data needs to be made public.

Also carried in BBC NEWS at http://news.bbc.co.uk/2/hi/health/7263494.stm

From PLoS Medicine  a peer review open access journal

At http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050045

Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration

Irving Kirsch^1*, Brett J. Deacon², Tania B. Huedo-Medina³, Alan Scoboria⁴, Thomas J. Moore⁵, Blair T. Johnson³

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.

Funding: The authors received no specific funding for this study..

Competing Interests: IK has received consulting fees from Squibb and Pfizer. BJD, TBH, AS, TJM, and BTJ have no competing interests.

Academic Editor: Phillipa Hay, University of Western Sydney, Australia

Citation: Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, et al. (2008) Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration. PLoS Med 5(2): e45 doi:10.1371/journal.pmed.0050045

Received: January 23, 2007; Accepted: January 4, 2008; Published: February 26, 2008

Copyright: © 2008 Kirsch et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abbreviations: d, standardized mean difference; FDA, US Food and Drug Administration; HRSD, Hamilton Rating Scale of Depression; LOCF, last observation carried forward; NICE, National Institute for Clinical Excellence; SD_c, standard deviation of the change score

* To whom correspondence should be addressed. E-mail: i.kirsch@hull.ac.uk

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 (NICE), and other licensing authorities have approved SSRIs for the treatment of depression, some doubts remain about their clinical efficacy. Before an antidepressant is approved for use in patients, it must undergo clinical trials that compare its ability to improve the HRSD scores of patients with that of a placebo, a dummy tablet that contains no drug. Each individual trial provides some information about the new drug's effectiveness but additional information can be gained by combining the results of all the trials in a “meta-analysis,” a statistical method for combining the results of many studies. A previously published meta-analysis of the published and unpublished trials on SSRIs submitted to the FDA during licensing has indicated that these drugs have only a marginal clinical benefit. On average, the SSRIs improved the HRSD score of patients by 1.8 points more than the placebo, whereas NICE has defined a significant clinical benefit for antidepressants as a drug–placebo difference in the improvement of the HRSD score of 3 points. However, average improvement scores may obscure beneficial effects between different groups of patient, so in the meta-analysis in this paper, the researchers investigated whether the baseline severity of depression affects antidepressant efficacy.

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.

Additional Information.

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050045.

• The MedlinePlus encyclopedia contains a page on depression (in English and Spanish)
• Detailed information for patients and caregivers is available on all aspects of depression (including symptoms and treatment) from the US National Institute of Medical Health and from the UK National Health Service Direct Health Encyclopedia
• MedlinePlus provides a list of links to further information on depression
• Clinical Guidance for professionals, patients, caregivers and the public is provided by the UK National Institute for Health and Clinical Excellence

List of Antidepressant Drugs with Medication Guides