The Limits of Prozac

Both treatment of depressed patients with both placebos and anti-depressant drugs is typically followed by statistically significant improvement. According to the author of a recent study on the subject linked below, the placebo response "accounted for more than 80 percent of the symptom alleviation observed in antidepressant-treated patients." The newest class of anti-depressant drugs, called and “selective serotonin reuptake inhibitors” (SSRIs), such as fluoxetine (Prozac), venlafaxine (Effexor), nefazodone (Serzone), and paroxetine (Paxil), provide an edge over placebos in only the minority of patients with the most severe symptoms.

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.

Bottom line:

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.

This affirms a prior similar study:

The placebo response identified in the new analysis parallels that reported in a previous assessment of FDA data directed by psychiatrist Arif Khan of the Northwest Clinical Research Center in Bellevue, Wash. The team analyzed 52 clinical trials of depression conducted between 1985 and 2000. Antidepressants outperformed placebos in only 25 of those trials.

Kahn notes, however, that clinincal trials which involve patients "who, typically, are seriously depressed but not suicidal and not suffering from other psychiatric ailments" may be atypically mild compared to those who seek a physician's assistance. This matters because a major justification for SSRI use (and for concerns about its effectiveness) revolves around the relationship between SSRI use (which dropped greatly after the FDA raised concerns about possible links to teen suicides) and suicide (a debate beyond the scope of this post).

In contrast, the new study's author asserts that "These clinical trials focused primarily on patients who, at the start of treatment, scored as having 'very severe' depression. Only a small number of patients started out with moderate to severe depression."

Kahn also notes that large apparent placebo effect may simply be a function of the fact that a before and after efficacy model fails to capture the fairly short duration of episodes of clinical depression in many patients. Thus, while most patients may see their depression resolve with or without drug treatment in a few months, drugs may improve the experience during the episode.

The results in the newer study linked below were based upon a meta-analysis of 35 studies on the subject (12 studies without data necessary to evaluate effectiveness were excluded), including unpublished results submitted to the FDA which tended to be less supportive of drug effectiveness than published studies. The meta-analysis did not consider the effectiveness of other classes of anti-depressant drugs such as tricyclics and monoamine oxidases.

While the new study may not be news to up to date pyschiatric professionals, it does contradict a widely held notion among members of the general public that Prozac and its cousins are appropriate for a wide swath of people suffering from depression.

From here via Science News (subscription limitations may apply).