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How Do SSRI Antidepressants Work?

In today’s post, I discuss the workings of one particular group of antidepressants. Specifically, I focus on selective serotonin reuptake inhibitors (SSRIs), which are antidepressants commonly prescribed to treat depression and sometimes anxiety disorders. Please note that what follows is a simplified version of complex biological events, so if you like to learn more about a particular aspect of this process, leave me a comment and I will try to direct you to a helpful resource that provides more detailed information (e.g., article, book, video).

Neurotransmitters and serotonin

Let us begin with learning more about neurotransmitters. What are neurotransmitters and what do they do? Neurotransmitters are chemical messengers produced by neurons (nerve cells); they help neurons communicate with other cells.

What does serotonin do? Serotonin is a major neurotransmitter and is known for its effects on mood, but that is not the only thing it does. Serotonin also influences sleep, appetite, sex, and several other functions.

We are now ready to learn about neurotransmission (how nerve cells communicate using neurotransmitters). We will consider what happens when one neuron (let’s call it Neuron A) wants to send a message to another neuron (Neuron B). Neuron A and B are not connected, so although the message can pass along each neuron’s body (as an electric impulsive), it can not go between them. What lies between the two neurons? A narrow space called a synaptic cleft.

Just a quick note about some terminology: In relation to the synapse, Neuron A is called the presynaptic nerve cell; Neuron B, the postsynaptic nerve cell.

A message passing from the presynaptic neuron to the postsynaptic neuron must cross the synaptic cleft—and given that this is a chemical synapse, the message needs to become a chemical to do so. How?

The presynaptic neuron produces neurotransmitters like serotonin, and releases them into the synapse; these neurotransmitters then cross the synaptic cleft and reach the postsynaptic neuron. There, they bind the appropriate receptors on that neuron. Then, the message once again becomes an electric impulse and moves down the postsynaptic cell until it reaches the next synapse and the next neuron.

Selective serotonin reuptake inhibitors (SSRIs)

I mentioned that selective serotonin reuptake inhibitors (SSRIs) inhibit the reuptake of serotonin, so it is time we learn what that means. Let us return to the synapse between Neuron A and Neuron B shortly after Neuron B has received the message from Neuron A. Imagine that the presynaptic neuron (A) now wants to send another message to the postsynaptic neuron (B), so it releases more serotonin into the synapse. But what happens to the serotonin molecules already there from the previous communication? Might they not overstimulate the postsynaptic neuron?

One way the presynaptic neuron tries to prevent complications caused by unbound serotonin accumulating in the synapse is by trying to collect or “reuptake” the serotonin molecules after a message has been relayed. So the unbound serotonin is transported back into the presynaptic terminal.

This is where SSRIs go to action: They try to block or inhibit this reuptake. That is why these medications are called Selective serotonin reuptake inhibitors. The result of preventing the reuptake is that more serotonin will be available in the synapse.

Perhaps you are wondering how increased serotonin in the synapse can be helpful to people with depression and anxiety disorders.

The serotonin theory of depression—which is a version of the chemical imbalance theory of depression—says that depression results from deficiency or malfunctioning of the serotonin system. Because people with depression are assumed to have less serotonin than healthy people, one way to fix this deficiency is by inhibiting the reuptake of serotonin and thereby increasing how much serotonin is available in the synaptic cleft.

How Do SSRI Antidepressants Work?

Arash Emamzadeh

Arash Emamzadeh attended the University of British Columbia in Canada, where he studied genetics and psychology. He has also done graduate work in clinical psychology and neuropsychology in US. Arash maintains a personal psychology blog and a blog for Psychology Today. Arash has a wide range of intellectual and artistic interests; he also maintains a poetry blog.

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APA Reference
Emamzadeh, A. (2019). How Do SSRI Antidepressants Work?. Psych Central. Retrieved on July 11, 2020, from


Last updated: 9 Aug 2019
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