Anti-Depression Medication Drugs Found to be of Little Benefit
Posted by: Kevin FlattAnti-depression medication prescription drugs: Study finds that there was virtually no difference in the improvement scores for anti-depression drugs and placebo in patients with moderate depression and only a small but clinically insignificant difference among patients with very severe depression.
The findings also show that the effect for very severe depression patients seems to be due to decreased responsiveness to placebo, rather than increased responsiveness to anti-depression drug medication.
Researchers from the U.K., America and Canada obtained data on all the clinical trials submitted to the FDA for the licensing of the new class of antidepressants -SSRIs. Selective serotonin reuptake inhibitors (SSRIs) are the newest antidepressants and include fluoxetine, venlafaxine, nefazodone, and paroxetine.
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 effectiveness.
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.
Before an antidepressant is approved for use in patients, it must undergo clinical trials that compare its ability to improve the Hamilton Rating Scale of Depression 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 Selective serotonin reuptake inhibitors (SSRIs) improved the Hamilton Rating Scale of Depression score of patients by 1.8 points more than the placebo, whereas the UK National Institute for Health and Clinical Excellence (NICE) has defined a significant clinical benefit for antidepressants as a drug-placebo difference in the improvement of the Hamilton Rating Scale of Depression score of 3 points.
However, average improvement scores may obscure beneficial effects between different groups of patients, so in the meta-analysis in this paper, the researchers investigated whether the severity of depression at the start of study affects antidepressant effectiveness.
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 Hamilton Rating Scale of Depression improvement scores for the drug and placebo groups in these trials.
They confirmed first that the overall effect of these new generation 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 Hamilton Rating Scale of Depression 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.
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 for depression 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.
Reference:
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. Copyright: © 2008 Kirsch et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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