Posted on February 17, 2018 by TMS Australia

People with depression have abnormal levels of neurotransmitters such as serotonin, dopamine and noradrenaline which all help the brain to send and receive messages. Neurotransmitters are reabsorbed by the cells that made them, which can mean there is an inadequate amount of them available to send and receive information around the brain. Blocking the absorption or reuptake of neurotransmitters with antidepressants can improve the level of neurotransmitters working in the brain to improve signalling and relieve depression symptoms.

You can think of this process as like an old cassette, where the lower levels of neurotransmitters create noise that impacts your listening enjoyment. Depression medication can decrease the noise and amplify the sound to restore your enjoyment.


The exact role of neurotransmitters in depression is not fully understood and it is possible that antidepressants also work on other systems in the brain. Despite this, antidepressants can be an effective treatment for depression.

How quickly do antidepressants work?

Depression medication takes at least two weeks to start relieving depression symptoms and sometimes several months before it is fully effective. It is important not to stop taking an antidepressant without first discussing it with a doctor.


What are the types of antidepressants (depression treatments)?

Antidepressants all work slightly differently to relieve depression symptoms. Depression treatments are grouped into classes depending on how they work. Each class affects different neurotransmitters which affects signalling in the brain in different ways. The differences in how they work can mean that some are more effective at relieving certain depression symptoms like lack of appetite, insomnia or anxiety, and it also means that they have different side effects.


Selective serotonin reuptake inhibitors (SSRIs)


These antidepressants are often one of the first medications prescribed when someone is diagnosed with depression. They stop the serotonin in the brain from being reabsorbed by surrounding cells so that more serotonin is available to participate in sending and receiving signals. They are one of the better tolerated antidepressants. Examples of SSRIs include citalopram, escitalopram, fluvoxamine, fluoxetine, paroxetine and sertraline.


Noradrenaline reuptake inhibitors (NARIs)

This class of depression medication includes reboxetine and works on nerve cells to stop noradrenaline and adrenaline from being reabsorbed so that they can participate in signalling within the brain. NARIs usually don’t cause any drowsiness but can have other side effects such as sweating, insomnia and as some sexual side effects.


Noradrenergic and specific serotonergic antidepressants (NASSAs)

These depression treatments, which include mirtazapine and mianserin, improve signalling by increasing the availability of two neurotransmitters, noradrenaline and 5-HT. They can be helpful for people who have sleep problems, anxiety or weight loss as part of their depression. They may cause weight gain.


Melatonergic agonist

Agomelatine is the most commonly used melatonergic agonist. It increases levels of serotonin and activates melatonin receptors in the brain to relieve depression symptoms and help with sleep problems.

Norepinephrine and dopamine reuptake inhibitors (NDRIs)

As the name suggests, this type of antidepressant which includes bupropion, stops norepinephrine and dopamine from being reabsorbed by the brain cells. The improved availability of these two neurotransmitters can relieve depression symptoms and these medicines may be particularly helpful when fatigue is present.


Norepinephrine and dopamine reuptake inhibitors (NDRIs)

These antidepressants are among the newer types and include desvenlafaxine, venlafaxine, duloxetine and milnacipran. They block the reabsorption of serotonin and norepinephrine which increases dopamine in the prefrontal area of the brain, an area important for mood regulation. They have less side effects than the older tricyclic antidepressants and are often prescribed for severe depression.


Tricyclic antidepressants (TCAs)

These medications are classified according to their chemical structure rather than the way they work. They were the first class of antidepressants and work by blocking neurotransmitter transporters to increase the neurotransmitter levels in the brain. TCAs have more side effects than the newer types of antidepressants and include amitriptyline, clomipramine, dothiepin, imipramine, nortriptyline, trimipramine and doxepin.


Reversible inhibitors of monoamine oxidase (RIMAs)

Inhibitors of monoamine oxidase work by stopping certain enzymes in the brain from destroying neurotransmitters. Moclobemide is an example of a RIMA and has fewer side effects than some of the other antidepressants. This antidepressant may be useful for treating depression when anxiety is present.


Serotonin modulators

Serotonin modulators such as vortioxetine are usually used to treat severe depression. They block one or more different receptors for serotonin in the brain so that it cannot be absorbed by these cells. An improvement in cognition is often observed with this type of antidepressant.


Australian depression treatment guidelines TMS a drug-free depression treatment How to treat severe depression
  • Beyond Blue. Antidepressant medication.
  • Khushboo SB et al. Antidepressants: mechanism of action, toxicity and possible amelioration. J Appl Biotechnol & Bioeng 2017; 3: 00082.
  • Malhi GS et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust New Zealand J Psych 2015; 49: 1-185.