Who benefits from antidepressants?

A new study published today in PLoS Medicine suggests that antidepressants only benefit some, very severely depressed patients.

“New generation” antidepressants, such as fluoxetine (Prozac) are widely prescribed for the treatment of clinical depression. However some studies have suggested that these drugs do not help the majority of depressed people get better by very much. Irving Kirsch, from the University of Hull, and his colleagues, studied this question in closer detail, looking at whether a patient’s response to antidepressant therapy depends on how badly depressed they are to start out with.

Kirsch and colleagues used a technique called “meta-analysis”, where they put together data on clinical benefit from all the trials submitted to the US Food and Drug Administration for four drugs: fluoxetine (Prozac), venlafaxine (Effexor), nefazodone (Serzone), and paroxetine (Seroxat / Paxil). (The researchers also wanted to include sertraline and citalopram, but couldn’t find all the relevant data for those two drugs). By including data from unpublished as well as published trials, the researchers set out to avoid bias that might come from non-publication of disappointing findings.

When the data from all of these trials had been put together, the improvement in depression amongst patients receiving the trial drug, as compared to those receiving placebo (dummy tablets), was not clinically significant in mildly depressed patients or even in most patients who suffer from very severe depression. The benefit only seemed to be clinically meaningful for a small group of patients who were the most extremely depressed to start out with. This improvement seemed to come about because these patients did not respond as well as less depressed patients to placebo, rather than responding better to the drug.

Irving Kirsch, summarising the paper, says: “Although patients get better when they take antidepressants, they also get better when they take a placebo, and the difference in improvement is not very great. This means that depressed people can improve without chemical treatments.”

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.

Citation: Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, et al. (2008) Initial severity and antidepressant benefits: A metaanalysis of data submitted to the Food and Drug Administration. PLoS Med 5(2): e45.

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

Source: Public Library of Science

   

• brant - Feb 26, 2008
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  The people involved in the last 5 school shootings certainly did not benefit.
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• COCO - Feb 27, 2008
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  maybe if we switched our drug laws with our gun laws this type of butchery would be less. Most people would be better off puffing a joint than doing Prozac and wee bit less chance of them going postal.
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• Skeletor - Feb 28, 2008
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  Unfortunately this is being reported uncritically as "Anti-Antidepressants are no better than placebo" by the media. There has been no mention of the flaws in the meta-analysis and likely bias by the authors. A meta-analysis is only as good as the information included in it and the inclusion of short trials (some under 6 weeks) make the conclusions uncertain.
  
  Some of these criticisms are explained in more detail in the comments section for this article:
  
  http://medicine.p...response&doi=10.1371/journal.pmed.0050045#r2149
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• SDMike - Feb 28, 2008
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  One of the problems with meta studies is that by averaging result small signals get lost. Depression is not a single "disease" rather, it is a symptom of several neurotransmitter, metabolic, and systemic diseases. "depression" is more like "high temperature" rather than "strep infection". Until physicians realize this they will continue to "treat" this symptom caused by a host of diseases with the same medications. Some patients will be helped, some will not, some will get worse, some will kill.
  
  Additional support for this hypothesis comes from the fact that each SSRI has different clinical effects and that each SSRI helps a subset of patients diagnosed as having the depression symptom.
  
  Preventing physicians untrained in neuropsychology from prescribing neuropsychoactive drugs would certainly be more effective than current gun laws.
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