The Frustration of Treating Depression

Depression is like a black cat in a dark room. Its hard to find it or even know if it really is a cat.

Depression is extremely frustrating. Mainly because we really have no idea how to define depression, making it very hard to even diagnose (read The Difficulty of Diagnosing Depression). It’s like being in a dark room, with a black cat and trying to pinpoint exactly where it is. This problem carries into treatment. If we don’t really understand depression, how can we design, develop and create a drug for its treatment? It’s like being in a dark room, with a dark cat and trying to shoot it. You may get a hit, but it might take a few tries – and sometimes to have any chance of shooting the cat you just have to use a cannon and watch out for the shrapnel.

The myth behind depression

I am sure that you have already heard that the cause behind depression is a chemical imbalance in your brain. Most specifically, a serotonin imbalance. So, most of the drugs used to treat depression are, in one way or another, linked to serotonin.

However (and this is a big however) in sixty years of research there is no clear scientific proof to back up this theory! There have been many studies that suggest that we don’t actually know what’s going on in the brain in a depressed state. In fact, we don’t even know what’s going on in the brain in a normal state, so it is really hard to assess what may be causing depression. There are no means to measure brain serotonin levels (which is different from blood levels), in living human beings, so we don’t actually know what the normal state for brain serotonin is; and how much it is altered in a depressed state, or if it is altered at all. And although drugs linked to this neurotransmitter appear to, sometimes, improve the symptoms associated with depression, it doesn’t directly mean that the problem was created by a deficiency in serotonin. In fact, there have been many studies to suggest that long-term antidepressants have depressogenic effects, and at least fifty percent of drug-withdrawn patients relapsed within 14 months, suggesting that the withdrawal symptoms are a “depression-like state”.

Sure, it may be a chemical imbalance but really, which chemical, and what kind of imbalance? What does the imbalance do to the overall functioning of the brain? How does a depressed brain behave?

Talking treatment

So, just how frustrating can treatment can be?

Only 30% of the diagnosed people will respond well to the medication in the first round. So, statistically speaking, treatment is not likely to work the first time around. You made that huge step of finding help, and it is not very helpful. This adds to the feeling of depression, as it can be maddening to feel you are not getting better, even though you are taking your pills and doing everything exactly like your physician told you.

You go “get help” second time. Your physician may add some more medication to the one you already have – increasing the chances of feeling side-effects. Or, the doctor might consider that you need a different drug altogether, and replace the one you are taking with another one. As we are talking about addictive medication, that is associated with many side-effects, none of the options above are very tempting. Relapsing is always on the table, and in fact, a 10-year study showed that 76% of people with un-medicated depression recovered without relapse relative to 50% of those treated.

Turning on the light

It is about time to re-analyze depression, by starting at the beginning: what is depression precisely? How can we find the cat, if we don’t know where it is – or if indeed it is a cat at all. It might be a cat for some people, a dog for others, or even an ant for the rest (you get the drift). It is very important to switch on the light in the dark room that is our brain to actually see what depression this, what it affects, and how it affects it, so that we can successfully develop drugs to treat its many variants. With considerable heterogeneity among individuals, this starts with understanding the spectrum of behavior of the normal brain.


Cindy Duarte Castelão has a degree in Human Biology and Health and an interest in mental health issues.


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