In an analysis of the data drug companies submitted to have their antidepressants approved by the U.S. Food and Drug Administration (FDA), researchers have concluded that compared with placebo, the four SSRI antidepressants studied appear to only help people with very severe depression.
“The response to placebo in these trials was exceptionally large, duplicating more than 80% of the improvement observed in the drug groups. In contrast, the effect of placebo on pain is estimated to be about 50% of the response to pain medication,” the researchers wrote.
The British researchers looked at data from 1987 to 1999 examining the effectiveness of fluoxetine (Prozac), venlafaxine (Effexor), paroxetine (Paxil or Seroxat), and nefazodone (Serzone). There was not enough complete data available for the researchers to examine three other commonly-prescribed selective serotonin reuptake inhibitors (SSRI) antidepressants. SSRI antidepressants work by affecting the amount of serotonin, a brain neurotransmitter related to mood and depression.
“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,” said Irving Kirsch of the University of Hull, the study’s lead author.
By looking at the datasets provided directly to the FDA by the drug companies themselves, the researchers were hoping to avoid other meta-analyses limitations, such as publication bias, multiple publications of the same dataset, and selective reporting in published studies. The study, however, did not analyze the hundreds of studies published since these drugs gained FDA approval, and so is limited to presenting a snapshot of the drugs’ effectiveness during the time period examined.
The researchers found that these 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.
“[T]he differences between drug and placebo were not clinically significant in clinical trials involving either moderately or very severely depressed patients, but did reach the criterion for trials involving patients whose mean initial depression scores were at the upper end of the very severe depression category,” the researchers wrote.
The study found that the therapeutic effect for these most severely depressed patients seems to be due to decreased responsiveness to placebo, rather than increased responsiveness to medication.
Given these results, the researchers concluded 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.
The study was published in PLoS Medicine.
Source: PLoS Medicine