You might have noted that yesterday was ‘Blue Monday’ – lauded as the most depressing day of the year. You might also be aware that Blue Monday was actually the construct of a Sky Travel marketing campaign several years ago, and is complete pseudoscience. Still, it seemed like as good an excuse as any to throw together this graphic, which looks at some of the different classes of antidepressants, and to discuss a little of how they work.
Before even considering the antidepressants, it makes sense to discuss what causes depression itself. Of course, there can be numerous personal reasons for depression, but what’s actually going on in the brains of those suffering from the condition? The short answer is that scientists still don’t really have a full answer to this question; however, there are several hypotheses with some evidence to back them up.
One of these hypotheses is termed ‘the monoamine hypothesis’. This involves the monoamine neurotransmitters, namely serotonin, norepinephrine, and dopamine, and suggests that depression is the result in a deficiency in the levels or function of these monoamines in the brain. Treatment with reserpine, a drug used for the control of high blood pressure, is often cited by purveyors of this hypothesis, as it is associated with depression and also a drop in levels of monoamine neurotransmitters. This evidence is still contested, however, and a number of studies have not found any difference in monoamine levels or function in patients with depression. Whilst this doesn’t rule out their involvement entirely, it suggests other factors may be at play.
Another hypothesis involves neurotrophins, proteins responsible for development and function of neurons in the brain. More specifically, it implicates Brain-Derived Neurotrophic Factor (BDNF), a neurotrophin responsible for the creation of neurons. Stress and pain are associated with a drop in levels of BDNF. Direct injection of BDNF has been shown to have an antidepressant effect in animal models, and all known antidepressants are also associated with an increase of BDNF. Again, however, not all evidence is in favour. Animals bred to have a deficiency of BDNF have not exhibited the depression and anxiety that would be expected.
Further systems in the body have also been implicated – for example, the endocrine (hormone) system. There is both supporting and conflicting evidence for each of the hypotheses, so it’s entirely possible that they are not mutually exclusive, and could co-exist as factors in depression.
Antidepressants can act in a number of ways, and considering the complex nature of depression, it’s unsurprising that there’s no single unifying mode of action. However, they do all impact on the monoamine neurotransmitters in some way; it is the manner in which they do this that varies. The precise role of the monoamines in depression may be unclear, but we do have an idea of their specific roles as neurotransmitters.
Serotonin is thought to be a contributor to feelings of well-being and happiness, as well as its other roles in sleep regulation, and regulation of intestinal movements in the body. Norepinephrine’s roles include attention and responding actions in the brain, and it is also involved along with epinephrine (adrenaline) in the ‘flight or fight’ response. Finally, dopamine is associated with feelings of pleasure and satisfaction, and is often termed as the brain’s ‘reward chemical’. All three of these chemicals in our brains can be affected by antidepressants.
The first class of ‘modern’ antidepressants to be discovered were the Monoamine Oxidase Inhibitors (MAOIs), which work by inhibiting an enzyme that breaks down the monoamine neurotransmitters, thus increasing their levels in the brain. These are now rarely used, as their toxicity is relatively high, and they have significant side effects. However, they can still be used if depression is unresponsive to other treatments.
The majority of other antidepressants work by inhibiting the ‘reuptake’ of the monoamine neurotransmitters in some way. Once neurotransmitters have performed their function of transmitting signals in the brain, they are removed by absorption by proteins. Many antidepressants work by preventing this removal, leading to increased levels of the neurotransmitter in the brain. Some antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRIs) affect only a single neurotransmitter – in this case, serotonin. Others affect noradrenaline and dopamine too.
The SSRIs, which include drugs such as Prozac and Zoloft, are currently the most commonly used antidepressants. This is largely due to the fact that a very high dose is required for toxic effects to be seen, and the side effects are mild compared to other antidepressants. These side effects can, however, include a reduced sexual desire; this is an effect common to the majority of antidepressants, with only a select few, such as bupropion, avoiding it.
Antidepressants are amongst the most widely used drugs – a survey by the Center for Disease Control & Prevention in 2007 found that they were the most commonly prescribed drugs in the US in 2007. In 2010, over 33 million prescriptions were written for Zoloft. It’s not just depression that they can be used to treat – they also find applications in panic disorder, generalised anxiety disorder, post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD).
(Medical disclaimer: this post is intended for information purposes only, and does not constitute medical advice.)
References & Further Reading
- Blue Monday – a depressing day of pseudoscience – D Burnett, The Guardian
- Basic & Clinical Pharmacology – B Katzung & others