A recent article in JAMA by Fournier et al. is a meta-analysis of antidepressant treatment effects assessed in relation to depression severity. Here's the reference:
The results show that antidepressants work significantly well, compared to placebo, only for very severe depression (corresponding to Hamilton Depression Rating Scale scores of at least 25).
The analysis is quite well-done, and the results are also presented in a graphical form clearly showing a linear increase in antidepressant effect as baseline depression scores increase.
The authors observe that antidepressants are most commonly prescribed to people who have milder depressions--a population in which they show that medications arguably do not work.
Here are a few of my criticisms of this study:
1) the duration of each trial included in the meta-analysis was between 6 and 11 weeks. In my opinion, depressive disorders are long-term, highly recurrent problems, which have a natural period over at least 6-11 months, not 6-11 weeks. Treatments to address mood disorders of any severity require much longer durations. The short duration could cause a significant under-estimation of treatment effects.
2) the study, like many, looks at "depression alone." In most real-life situations, outside of a research study, individuals have several different problems, such as mild depression + social anxiety, or mild depression + panic attacks, etc. The presence of other symptoms, particularly anxiety symptoms, most likely would increase the likelihood of antidepressants helping.
3) Milder depressions, just like more severe depressions, may actually improve more consistently with a "second step" such as combination with psychotherapy, or combining two different antidepressants. The mildness of a medical syndrome does not necessarily mean that the effective treatments need only to be "mild."
4) Milder depressive syndromes may be more prone to misdiagnosis.
5) current "resolution" to measure treatment effects in depression is quite poor. "Depression" is a very broad category. An analogy could be considering "abdominal pain" to be a diagnostic category. If "abdominal pain" is the only category, and is simply rated on a severity scale (rather than subcategorized to obtain a precise diagnosis), and the treatment offered for "abdominal pain" is appendectomy, then we would probably see no difference in treatment effectiveness between appendectomy and placebo. This is because appendectomy is only effective to treat appendicitis (a subset of the abdominal pain population), and is either ineffective or harmful in treating abdominal pain patients without appendicitis (except, perhaps, for those patients who have a placebo improvement of psychosomatic or factitious abdominal pain, an improvement which they attribute to having surgery).
We currently do not have the science to subcategorize depression in a more clinically meaningful way (there are subcategorization schemes, but they don't have much relevance in terms of treatment).
But we do have a research method which could improve "resolution":
-instead of comparing two populations of depressed individuals, one group receiving antidepressant (or some other treatment), and the other receiving placebo (or some other alternative), the study design could instead be to offer every individual courses of placebo, alternating with antidepressant (or "treatment one" alternating with "treatment two"). Each course of treatment would have to last an adequate length of time. The analysis would aim to show whether there is a subset of individuals who respond to the antidepressant, or a subset of individuals who do better with placebo. The averaged results over the whole group might show that antidepressant effects do not differ from placebo (just like appendectomy might not differ from placebo in treating "abdominal pain"), but the individualized result could show that some individuals improve substantially with the antidepressant (just like appendectomy would save the lives of the small group of "abdominal pain" patients who have appendicitis).
In the meantime, though, I think it is reasonable to recognize that antidepressants are less consistently helpful when symptoms are less severe.