Medication, Phenomenology and the Nocebo Effect

A great recent paper by Gibson and colleagues undertook a thematic analysis of people's responses to being asked about taking antidepressants. Some of what they described was very negative. This is not a surprise (it is well known that many antidepressants have a significant side effect profile), though it is important that it has been documented. Here, for example, is a striking description:

Each one has had a worse effect than the previous…. I can’t remember them all. It started with memory loss then progressed to me becoming borderline catatonic staring at the wall for hours unable to stand up. Within a few weeks and genuinely terrified. It was a relief to go back to the misery of depression after these experiences

In addition to descriptions of what we can designate as direct negative physiological effects, another negative theme that emerged was "loss of authenticity/ emotional numbing". This is a more slippery experience; a sort of phenomenological unease arising from taking medications. Authenticity is an important part of our sense of who we are. To interfere with it may be less physically dangerous than a side effect like weight gain, but feels somehow more metaphysically perilous. Take my body, but leave my self alone!

The authors of the study point out "This research points to the inadequacy of asking the simple question: ‘Do antidepressants work?’ Instead, the value or otherwise of antidepressants needs to be understood in the context of the diversity of experience and the particular meaning they hold in people’s lives." I agree, but I think even this form of the question can be complicated further.

We have become accustomed to thinking about the effects of antidepressant medications in terms of the placebo effect. Since (at least) a famous meta-analysis by Irving Kirsch (and a subsequent book), many have suggested that the benefits of antidepressants are not the result of an positive, active drug effect, but the mysterious workings of the various expectancy effects we call "placebo".

It's a popular idea, albeit one that has become fraught with controversy. I am not going to wade into the question of how effective antidepressants really are (if you want to think about that then you are in for a long puzzling road. You could do worse than to start with James Coyne's provocative critique of Kirsch here). but I do want to suggest that, when it comes to expectancy effects and antidepressants, there may be a kind of asymmetry in how we customarily think.

Drugs also have nocebo effects; harmful outcomes that arise from the expectations of the people taking them. The nocebo effect (placebo's evil twin) is not something to be fooled around with. For a vivid account read this case study of a young man who needed hospitalisation after he overdosed on the inert pills he was given during an antidepressant trial. If expectations about a sugar pill can do that, then without doubting the flat reality of antidepressants' severe physical effects, we might wonder whether some negative effects, including feelings of phenomenological unease, could also result from a such a phenomenon.

There is a veritable culture of suspicion about the phenomenology of antidepressants, and a strand of cultural commentary on psychiatric medications that sounds a shrill moralising note. Taking medications for depression is regarded by some as an inherently suspect thing to do. Two notorious skeptical pieces in The Guardian (by Will Self and Giles Fraser), around the time of the publication of DSM-5, both hinted at the idea that taking antidepressants was the result of false consciousness:

At worst, they pathologise deviations for normalcy, thus helping to police the established values of consumer capitalism, and reinforcing the very unhappiness that they purport to cure.

It is hard to imagine that none of this would loop back round and influence people's experiences of what it is like to take medication. Ineeded, psychiatrist Linda Gask writes beautifully about the internal struggle over self-authenticity that can result from these ideas:

There are times still when I wonder whether the medicated me I’ve been for so long is the ‘real’ me, or are these tablets simply suppressing the person I truly am?

Contrast the Gibson study with the miraculous seeming accounts of the experience of taking SSRIs when they were brand new. Peter Kramer's 1994 "Listening to Prozac" included the now famous (and oft-derided) claim from one patient that the drug made them feel "better than well".

Could it be that when drugs first appear, they not only benefit from a sort of placebo boost (in virtue of their novelty value), but also from the absence of a culturally inherited, nocebo baggage? Research on this question seems just as important as teasing out the beneficial effects that arise from inert substances. If there are such effects, what are the moral obligations that arise for how we talk about treatments and shape the expectations of those who take them?