When did people stop caring about aetiology? The case of antidepressants

The time is 11.30am on 1st March 2018. I have a meeting at midday. That gives me 30 minutes to articulate what feels like a fire burning in my stomach. Last week I saw the release of paper in which the authors triumphantly declared that ‘antidepressants work’. I read the paper, I read the headlines and I read the reaction on social media. This is such a hot and sensitive topic that I want to present a slightly different angle.

In other words, I am not going to talk about how the authors, via their universities, receive payments from pharmaceutical companies, I am not going to talk about how a large percentage of the studies included in the meta-analysis were funded by pharmaceutical companies, I am not going to talk about how the authors have a sketchy history of concluding efficacy for a drug that was later shown not to work (Prozac for children and Sertraline for adults), I am not going to talk about how much of the raw data from the studies included in the meta-analysis is unobtainable, and I am not going to talk about the well-documented potential side of effects of taking antidepressants. If you want to know about any of those things, then I include a list of interesting webpages at the end of this blog.

Nope, I am going to talk about something different. I am going to talk about the importance of understanding what underpins a problem before a treatment is developed for it. This angle, the very angle that blows my mind in the context of anti-depressants, seems to be neglected in many of the commentaries that I have read. Let me explain it to you. Imagine that you had social anxiety and that you were invited to a party. Imagine I wanted to develop a novel treatment to help you with this problem. So at about 5pm on the day of the party I came to your house with a bottle of wine. You drank the bottle, you went to the party and you reported no social anxiety. The next day I write the empirical article entitled: ‘Wine works for social anxiety’. A newspaper reporter then asks me why it worked. My response “well, people with social anxiety have low levels of alcohol in their blood and so all we had to do was a bit of re-balancing”.

That is the exact story of anti-depressants. It is all backwards: the treatments were developed first and then the theories as to how they worked came afterwards with little empirical backing. There is no conclusive evidence that people with depression have a chemical imbalance before they start taking medication. In other words, we are giving anti-depressants to people with the promise of curing depression and yet we don’t know what is causing the depression in the first place. The aforementioned meta-analysis illustrates this in the most obvious way. It concluded that 21 different anti-depressants work! Twenty-one! How is that possible? How can 21 different drugs that impact our bodies in 21 different ways all ‘work’ to treat one disorder? My point; surely we need to know the exact nature of the chemical imbalance before we can start to shout from the rooftops that anti-depressants should be the way to treat people with depression?

People spend so much time debating the outcomes associated with anti-depressants (and therapeutic approaches to mental health more broadly) but they are asking the wrong questions. Studies that measure only whether an approach works are hard to trust. Why? Because many different factors might account for the change in outcome, ranging from a placebo effect, to losing weight, to finding a partner, to starting a talking therapy or even winning the lottery. For that reason, it is more important to figure out how an approach works relative to the problem it fixed. In other words, I need someone to find me an anti-depressant study that (1) shows a specific chemical imbalance at pre-intervention (2) shows that a particular drug reliably changes the levels of those chemicals and (3) shows that the improvement in chemical levels is what mediates the improvement in symptomology.

Don’t get me wrong here, I am not saying that there aren’t studies showing that anti-depressants help people in the short-term, and I am not saying that you should choose talking therapies because they too have their problems (in fact talking therapies have some of these exact issues such that efforts are being made to highlight the importance of psychologically active processes). What I am saying, however, is the following: in the context of anti-depressants, can we please do more to investigate the precise nature of the ‘chemical imbalance’ before we develop drugs to treat it? If we do not take the time to do this then we will continue to treat biological systems that have nothing wrong with them with drugs that can be potentially harmful. My gut tells me, if such research was ever conducted, that no chemical imbalance will be found. And maybe, once we know that, we might be more reluctant to accept an anti-depressant as anything more than a tonic for us when we are in a deep hole.

Interesting Anti-depressant Blogs