Are antidepressants effective?

Depression can be defined as both a syndrome and a disorder. As a syndrome it involves episodes of sadness, loss of interest, pessimism, negative beliefs about the self, decreased motivation, behavioural passivity, changes in sleep, appetite and sexual interest, and suicidal thoughts and impulses. As a disorder it comes in two forms. The unipolar type, which affects about 10% of men and 20% of women, includes only episodes of depression.

This is the type we’re going to cover in this article, in particular Major Depression Disorder, described in the DSM-IV. Tons of research has been done on the causes of depression. But since the brain is a very complex organ and we have little to none understand on how it really works, throw light on disorders related to the mind is quite difficult.


There are many types of antidepressants and in this article I will cover only selective reuptake inhibitors, which are by far the most commonly prescribed. I hope this make you understand better what they are and how they work.

It’s easy to jump to conclusions: the definition of Major Depression Disorder is too broad: the diagnostic guidelines are made based on a checklist of mental symptoms. But since we’re all different, those symptoms can change between individuals, depending on our personality and way to see the world (that’s why the list is somehow flexible on the symptoms). In any case, diagnose is not based on physical tests, it’s not always easy to find physical patterns when we talk about mental disorders, and this somehow reinforce the idea on how poorly this condition is understood. As far as we know there could be many causes beneath depression: biological, genetical, psychological, ambiental, cognitive or a combination of all. The brain for sure has multiple layers of complexity.

Brain chemicals are certainly part of the cause, but as an explanation is way too simple. However, that’s exactly what antidepressants act on: neurotransmitters.

Depression has been linked to problems or imbalances in the brain with regard to the neurotransmitters serotonin, norepinephrine, and dopamine. The evidence is not really there because it is very difficult to actually measure the level of neurotransmitters in a person’s brain. What we know is that antidepressant medications (used to treat the symptoms of depression) are known to act upon these particular neurotransmitters and their receptors. The neurotransmitter serotonin in particular is involved in regulating many important physiological (body-oriented) functions, including sleep, aggression, eating, sexual behaviour, and mood.




But what are neurotransmitters? Well, our brain based on an electrochemical system. Neurons, the nerve cells that compose the brain, are connected in a big network and communicate with each other through electrical and chemical signals. In a very simplistic way: this chemical process have place when a neuron sends neurotransmitters to another. The receiver cell have receptors that get stimulated by those molecules, and then they’re reuptaken to be used in future interactions. What antidepressants exactly do is to neutralize some of the molecules involved in the reuptake process. In this way the neurotransmitter stays longer in contact with the receptor and makes the signal stronger.

The most commonly prescribed flavours of antidepressants are: selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs). Those are drugs that act specifically on serotonin or serotonin and norepinephrine reuptakers. But are those effective?

The essential facts about antidepressant efficacy are not in dispute. In double-blind, randomized controlled trials (meaning that patients are randomly assigned to receive either drug or placebo, and neither patient nor clinician knows who gets what) antidepressants show a small but statistically significant advantage over placebos.



However, the reinforcement of the signal on receptors don’t last forever: the brain readjusts to this change. For this reason some experts believe that the efficacy of antidepressants is not strictly related to its effects on neurotransmitters.

In other words: studies say that antidepressants work, but we’re not sure why! A quite popular theory is the neurogenesis.

Brain scans revealed that people affected by this illness have some areas of the brain reduced in volume, mainly prefrontal cortex. Why does this happen? The neurogenesis theory says that people not suffering from depression have a balance in degradation and regeneration processes in the brain. The degradation process refers to the breaking down of nerve cells, while regeneration refers to the formation of nerve cells. Depressed patients show greater activity in the degradation system, which explains why brain structures are reduced. Selective reuptake inhibitors are linked to a boost in neurogenesis with a recovery of normal size in the affected parts.



Ok, now we know that antidepressant are useful, however it’s important to consider that this is not a final solution, and not always effectively make all the symptoms disappear.

What about therapy? On this front, the most broadly recognised as an effective method is the cognitive behavioural therapy (from now on, CTB).

The evidence shows that that CTB is as efficacious as SSRI/SNRI, and that its effects are more enduring. Clinical experience suggests that patients treated with CTB first learn to apply the strategies each time they experience their habitual tendency to process information in a negatively biased way. They’re able to acquire and then carry out ‘compensatory skills’ needed to fight their disorder. Repeated application of these skills seems to result in the alteration of the patient’s general beliefs about themselves, as inferred from an increasing tendency, over time, for patients’ prepotent reactions to be free of the negative biases. This process is referred to as the ‘accommodation’ of beliefs to new evidence. Statistics show that the most effective way of treating depression is the combination of therapy and medication. The rate of recovery is higher than when only one method is used.

In conclusion, we don’t really know how depression work, we don’t really know how antidepressants help. We know that depression exists and antidepressants work for some cases, and the best strategy is to cover most fronts as possible combining therapy with medication.




N. Gentile

Software engineer, science lover. Collaborated in several European Space Agency (ESA) projects and European Commission scientific R&D projects mainly related to earth observation. Currently working in video-game behaviour forecasts for one of the most influential companies of the industry.

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