In the shower just now I was musing idly about antidepressants and the placebo response …. As you do.
Some studies show that bipolar depression responds less well to antidepressant medication than does unipolar depression. Some find that it responds as well or even better. Conflicting results like those are always odd, but there are often trial issues that have an impact. However, I wonder whether they were examining different antidepressant agents. Many of us have the idea (more or less strongly-held) that different ‘types’ of depression respond differently to different classes of antidepressants (for example, serotonergic antidepressants such as fluoxetine being more useful for the psychological depressions, and noradrenergic antidepressants such as nortriptyline being more useful for melancholia) – though it has to be said this is only from clinical anecdote/experience, and (some) expert opinion; I’m not aware of any clear literature on the subject.
I also wonder how this ties into the recent meta-analyses which claim to show that antidepressant medications are no better than placebo for mild to moderate depression (despite actually only examining small numbers of trials from only a few medications). If a depression occurs as part of a bipolar disorder, it is a manifestation of a very biological illness. Unipolar depression covers a wide range of disorder, from frankly biological (your classic melancholia) through to primarily a psychological problem at the other end. It would not be at all surprising that these conditions would respond differently to a biological treatment (antidepressant medication). It is also quite likely that the more severe end of depression in the trials (where antidepressants were superior to placebo) contains more melancholia and bipolar depression than would be found in the mild end (where antidepressants might not be any better than placebo). Given that, it might not be too surprising that there was a differential degree of efficacy shown across the range of severity. It’s likely similar to the way that ECT is most effective for the most severe depressions, and is less useful for milder depression.
In any case, I think it definitely warrants a closer look.
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