Mental health issues like depression can be some of the most challenging health related problems we can ever face. Those who suffer from depression deserve the best possible treatment and support available. With the number of prescriptions for anti-depressants having risen significantly over the last few decades and 1 in 11 adults in the UK currently being prescribed antidepressants, how do antidepressants actually work?
Depression is often commonly explained as a “chemical imbalance” or a “serotonin deficiency”. In reality, it isn’t that simple and can be associated with a wide range of possible causes ranging from genetic vulnerability, stressful life events, and faulty mood regulation by the brain. Antidepressants increase the activity of certain chemicals in our brain called neurotransmitters, that pass signals from one brain cell to another. Increasing levels of neurotransmitters like serotonin and noradrenaline have been shown to improve mood and emotion, although, this process itself is not fully understood. The basic theory is that keeping levels of these neurotransmitters high could improve communication between the nerve cells and strengthen the circuits in the brain that regulate mood.
The most common types of antidepressants are reuptake inhibitors. Reuptake is the process by which neurotransmitters are naturally reabsorbed back into the nerve cell from the synapse (the space between nerve cells) after being released to send messages between these nerve cells. A reuptake inhibitor, unsurprisingly, inhibits the reuptake of these neurotransmitters back into the nerve cells, so that they temporarily remain in the synapse. Common types of reuptake inhibiting antidepressants are SSRIs (selective serotonin reuptake inhibitors), SNRIs (serotonin and norepinephrine reuptake inhibitors) and NDRIs (norepinephrine and dopamine reuptake inhibitors), which are the most commonly prescribed in the UK.
Other types of antidepressants include tetracyclic and SARI antidepressants. Tetracyclic antidepressants work by stopping neurotransmitters from binding to specific receptors on the nerves, resulting in a build-up of neurotransmitters in the synapse. SARI (Serotonin Antagonist and reuptake inhibitor) antidepressants appear to both prevent the reuptake of serotonin and also prevent serotonin particles from binding at certain undesired receptors, redirecting them to other more beneficial receptors on nerve cells involved in circuits that regulate mood.
Older types of antidepressants are tricyclics and MAOIs (monoamine oxidase inhibitors); these are much less common as they can result in serious side-effects such as nausea, diarrhoea, low blood pressure, headache, dizziness, difficulty urinating, and insomnia. However, they also happen to be some of the most effective antidepressants and so are only prescribed to people with treatment-resistant depression.
Tricyclics work like reuptake inhibitors, by blocking the reabsorption of serotonin and epinephrine back into the nerve cells. An enzyme called monoamine oxidase is involved in removing the neurotransmitters norepinephrine, serotonin and dopamine from the brain. MAOIs prevent this from happening, resulting in the levels of these neurotransmitters getting a boost.
Patients treated with antidepressants show substantial improvement; however so do those treated with a placebo drug. In 1998, a study of 2318 patients claimed that the placebo effect could be accountable for 75% of the effects of antidepressants. Whether their effect is due the placebo effect, or due to actual neurological effects, antidepressants still produce the desired outcome and seemingly outperform the placebo effect.