Does sertraline permanently alter brain chemistry? (3+factors at play)

In this article, we will discuss whether sertraline can permanently alter your brain chemistry. We will also discuss some research studies on the long-term effects of sertraline on the brain and what factors can contribute to this effect.

Does sertraline permanently alter brain chemistry?

Sertraline does not typically alter your brain chemistry permanently, and the changes made by the antidepressant are reversed eventually after you stop taking it. 

Sertraline, a selective serotonin reuptake inhibitor, is primarily used as an antidepressant (1,2). This medication is well known for increasing the availability of serotonin, an excitatory monoamine neurotransmitter, in the brain to bind to its receptors. 

This increased serotonergic activity helps overcome the symptoms of depression, anxiety, and several other mental health-related problems (1). Now, this alteration in brain chemistry is considered temporary, and your brain does go back to normal when you stop taking the medication. 

However, it is important to note that the dosage strength and the overall duration of sertraline treatment can make a huge difference. Also, people are different, and their bodies adapt to sertraline in different ways. The underlying factors should also be considered in this case. 

Such things collectively determine how one’s body adapts to the antidepressant and how dependent the availability of serotonin becomes on it. 

Furthermore, long-term use of sertraline can affect your brain chemistry, which may take much longer to get back to its initial state. So, the long-term use of sertraline should be reserved for chronic cases, and one should never make any changes to their prescription without professional help.

What does research suggest?

There is limited research on the permanent effects of sertraline on brain chemistry, and more research is required for a proper conclusion. 

However, research does suggest that long-term use of sertraline can affect the neural structures in the brain, and several animal models were used to study this effect of the antidepressant (3). 

Research also suggests that long-term use of antidepressants, in general, might not be beneficial for everyone, and the drugs may not provide relief in the symptoms after some time (4). 

One research study indicated that antidepressants, in some cases, can significantly affect normal brain functions instead of regulating them (5). The exact mechanism through which it happens or the exact duration after which one should expect such changes in the brain has not been explained yet (5). 

However, more research is needed to completely understand the long-term effects of antidepressants, including sertraline, on brain chemistry. 

One research study showed that the long-term use of sertraline can cause the enlargement of the middle frontal gyrus – a part of the brain involved in memory, learning, cognition, emotional processing, etc (6). 

These studies indicate that sertraline can make long-term changes in your brain. Therefore, the chronic use of sertraline should be avoided if not necessary.

What are the long-term psychological effects of sertraline?

The long-term psychological effects of sertraline include: (1,2)

  • Extended use of sertraline may be linked to emotional blunting, where individuals may experience a reduction in the intensity of emotions, both positive and negative.
  • Some individuals may report difficulties with concentration, memory, or cognitive function.
  • Prolonged use of sertraline may impact sleep patterns, leading to difficulties falling asleep or staying asleep. This can contribute to fatigue and changes in overall mood.
  • In some cases, individuals may report feelings of depersonalization or detachment from themselves as a long-term psychological effect of sertraline.

What factors can influence your brain chemistry while taking sertraline?

Several factors can influence your brain chemistry while taking sertraline, including:

Dosage and duration of treatment

The dosage and how long you take sertraline can significantly influence your brain chemistry. High doses over an extended period can contribute to alterations in brain function and structure.

Underlying health conditions

Individuals with pre-existing brain conditions may be more susceptible to the effects of sertraline. It’s important to rule out underlying psychological conditions before using sertraline.

Concomitant use of other medications

The interaction between sertraline and other medications can affect brain chemistry. Some drugs, when taken together, may exacerbate side effects or produce unexpected outcomes.


Genetic factors play a role in how individuals respond to sertraline. Genetic variations can influence how the drug is metabolised in the body and how the brain responds to its effects. Some individuals may experience different or adverse reactions based on their genetic makeup.

What to do if sertraline affects your brain chemistry?

If you think sertraline is affecting your brain chemistry in any way or if it’s causing psychological side effects, please reach out to your doctor. 

In general, sertraline is supposed to alter your brain chemistry by changing serotonin levels, which are involved in various psychological functions and signalling within the brain. 

This change is the reason why sertraline and its fellow SSRIs work and manage symptoms associated with various mental health conditions. However, if your doctor believes that sertraline is not the best choice of antidepressant for you, they will consider alternative treatment options.

What are the safer alternatives to sertraline for your brain?

Other SSRIs, such as fluoxetine, escitalopram, paroxetine, fluvoxamine, etc, can be used as alternatives to sertraline if your body does not respond well to it. However, it is important to note that all antidepressants temporarily alter brain chemistry, and that’s how they work. 

SSRIs alter the levels of serotonin, which is involved in various brain functions and signalling within the brain. This effect is responsible for generating a therapeutic response to these medications. 

So, you can’t really expect an antidepressant to not alter your brain chemistry as it won’t help your symptoms otherwise. However, some antidepressants are considered safer than others. 

Apart from SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs) and some atypical antidepressants are also considered to be safer (7), compared to tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), which have more complex mechanisms of action and have a less safe side effect profile. 

Among SSRIs, SNRIs, and atypical antidepressants – SSRIs are considered safer because of how they work and their lesser affinity to bind to other receptors in your body. It is a known fact that the more receptors a medication binds to, the more complex the side effect profile becomes. 

SSRIs primarily work on serotonin levels, as opposed to SNRIs, which work on both serotonin and norepinephrine. Therefore, based on the mechanism of action, SSRIs are considered the safest antidepressants. 

However, an individual’s response to medications can make a huge difference. So it’s best to rely on your doctor’s expertise and stick to the recommended antidepressant. 

As a pharmacist, I always advise my patients to stick to their doctor’s direction and help them understand the proper use of the medication. 

I also talk about how determining the best antidepressant for you could be a trial-and-error process and one may try multiple antidepressants before they find the one that works best for them. So don’t be disheartened if your current antidepressant is not helping your condition. Just discuss your concerns with your provider.


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