Reporting Bias Rife in Antidepressant Studies for Anxiety

Pam Harrison

| April 07, 2015
My Alerts

Click the topic below to receive emails when new articles are available.

The vast majority of studies evaluating antidepressant efficacy for the treatment of anxiety disorders that are judged by the US Food and Drug Administration (FDA) as positive are published. However, it's a different story for nonsignificant studies, results of a new meta-analysis show.

Investigators at the University Medical Center Groningen, the Netherlands, found that trials that the FDA deemed positive were five times more likely to be published compared with trials deemed not positive. Furthermore, they found evidence for study publication bias (P < .001), outcome reporting bias (P = .02), and spin (P = .02).

The findings, investigators say, provide a skewed view of antidepressant efficacy.

"Antidepressants have value in treating anxiety disorders, but they are not 'miracle drugs,' and there is less evidence to support their efficacy than what appears from the published studies," Annelieke Roest, PhD, told Medscape Medical News in written correspondence.

"It is important that physicians have a realistic view of the efficacy of these drugs so they can make a well-justified decision when prescribing these medications," she said.

The findings were published online March 25 in JAMA Psychiatry.

Skewed View?

The investigators note that there is "strong evidence that significant results from randomized clinical trials are more likely to be published than non-significant studies.

"As a consequence, published studies, including meta-analyses, may overestimate the benefits of treatments while underestimating their harms, thus misinforming physicians, policy makers, and patients."

The researchers examined reporting biases in double-blind, placebo-controlled trials on the pharmacologic treatment of anxiety disorders and quantified the extent to which these biases inflate estimates of drug efficacy.

They identified phase 2 and 3 double-blind, placebo-controlled trials registered with the FDA and conducted in pursuit of marketing approval of second-generation antidepressants for the treatment of generalized anxiety disorder, panic disorder, social anxiety disorder, posttraumatic stress disorder, and obsessive-compulsive disorder.

Studies involving seven selective serotonin reuptake inhibitors and two serotonin norepinephrine reuptake inhibitors were evaluated.

Of the 57 trials identified by researchers, findings from 41 of them (72%) were judged to be positive by the FDA.

However, 43 of 45 (96%) of the articles published in the literature were positive (P < .001).

This suggests that trials the FDA determined to be positive were five times more likely to be published in agreement with that determination compared with trials determined to be not as positive by the FDA (risk ratio, 5.20; 95% confidence interval, 1.87 - 14.45; P < .001).

Sixteen of the 57 trials identified by investigators (28%) were not judged to be positive by the FDA, and seven of these trials (44%) were not published. Continue Reading

Post as:
This conversation is currently closed to new comments.
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
|  Family Medicine 38%20spec%2010

Antidepressant and antianxiety meds have very soft endpoints and placebo effect which make it very easy for drug companies to manipulate the true effect, since these are chronic meds there are potentially billions of dollars in profit at risk.  Possible negative effects (GI bleed, rage response, increased falls, EKG changes, increased dementia risk) and long term effects are ignored or sometimes  hidden.  These can be very useful medications.  But they should be used with care and for the indications, length of time, and age range for which they have been studied.

|  Psychiatry/Mental Health 61 spec 10

Your author has  misstated the conclusion of the JAMA article.

You have reported that "The findings... provide a skewed view of antidepressant efficacy."

This is exactly what the findings of the metanalysis  in JAMA did NOT do!.

Here is the accurate quote from JAMA: 

"Conclusion ...reporting biases were present for trials on the efficacy of FDA-approved ...antidepressants for anxiety disorders. ALTHOUGH THESE BIASES DID NOT SIGNIFICANTLY INFLATE ESTIMATES OF DRUG EFFICACY, [caps my own], reporting biases led to significant increases in the number of positive findings in the literature." 

It is worth repeating: ... "these biases ...did NOT significantly inflate estimates of drug efficacy. "

May I make a plea for more accurate reporting? 

This is irresponsible  journalism: publishing  misinformation and  biassed conclusions of the author that pose as "analysis". It does a great disservice to your readership and to the larger scientific community.

Please, if you are going to pretend to be a medical journal,  hire editors  who can accurately read a scientific article and get it right!

|  Psychiatry/Mental Health 61%20spec%2010

I remember a study I read as an undergraduate in the 50's  about psychology experiments.  The statistical tests used all had the assumption that  the experiments were to repeated to make the conclusions valid.  Almost none ever were.  And I believe that negative results wer much less likely to be reported or published.  Things don't change much. 

|  Other Healthcare Provider 15%20prof%2015

This is scary but does not suprise me..Its all about money. Everything is about money.

|  Health Business/Administration 13%20prof%2013

I found this article very interesting.  I, personally, did not find the observations made in the article all that surprising, however.  The bias of publication of positive results versus negative results will likely be found in about any serious publication.  I think it would be more interesting to look at the reason for the bias.  

Scientists, like myself, are motivated to publish results for a set of reasons.  Many of those reasons are not satisfied by publication of work that is inconclusive or negative regarding the purpose of the study.  If we do publish the work we likely will spin the results in a positive light.  It' human nature.

|  Registered Nurse (RN) 13 occ 12

Lies!  Damned lies and statistics!

Its not that they just don't work - they do so much harm!  Apart, that is, for the shareholder dividends.

A case of the Emperor's New Cloths - think about it!

|  Health Business/Administration 13%20prof%2013

@P S I disagree.  They do work.  I am living proof.  Sure, there are problems.  I hate taking the stuff but I would be DEAD if I didn't.  Yes, they do not get to the root cause and no one said they did (if they are honest).

|  Psychologist 23%20prof%2023

Is this surprising?  The FDA's funding is dependent on the pharmaceutical companies.  Less and less funding comes from government, so the jobs of government employees at the FDA are increasingly dependent on industry funding.

There is also a possibility, that people think no positive finding means that there's no need to report it, but the result is that people don't know of the number of tests that failed to find an effect.

Is this concerning?  Yes.  People have learned to see the FDA as a scientific organisation, unbiased by commercial interests and acting in the role of consumer protection.  There would now appear to be some conflicts of interest.

No wonder doctors believe in these drugs even though the evidence suggests that they are of little use, and in fact can cause extreme harm over both the short and long term.  We all know that they don't cure the problems, just mask them for a while.  Once the drug is ceased, the problem returns only bigger, as the person has depended on the drug to cope, instead of learning better problem-solving and coping skills.

|  Nutrition 194%20spec%2010

The problem with the marketing of antidepressants is that they are always portrayed as magic bullets for the relief of depressive symptoms. That, of course, is incredibly simplistic and is deliberately designed to fool even the most astute Physician that just one pill will fit the bill. 

But the brain & body are far more sophisticated than that. Hence, the high placebo levels.

SSRIs & SNRIs are useful drugs, as part of an overall treatment strategy. But they should NEVER be used alone. These days, such prescribing should virtually amount to medical malpractice.

Major depression demands thorough clinical investigation to uncover the underlying causes.

For example, does the patient have hypothyroidism (TSH > 3.0) or suffer from iron deficiency (ferritin < 50)

Are they in renal failure with an eGFR < 60 or worse; or do they have a malabsorption syndrome so that available amino acid precursors (tyrosine, phenylalanine, tryptophan) are simply not available in sufficient quantities for dopaminergic & serotonergic neurotransmission respectively. What about testing for polymorphisms in COMT, resulting in elevated norepinephrine levels with accompanying anxiety. What about testing salivary cortisols x4 over a 16hr time frame. One can even measure the six major neurotransmitters in urine and determine which pathways actually need metabolic support.

If you don't do the right tests, you don't get the right answers and your patient will suffer the consequences.

|  General Practice 40%20spec%2010

Refreshing resume. It timely reminder as one see in clinical practice;considering the patient's well-being is paramount !

Latest in Psychiatry

Authors and Disclosures


Pam Harrison

Freelance writer, Medscape

Disclosure: Pam Harrison has disclosed no relevant financial relationships.