Does Sertraline increase GABA? (3+ factors)

In this article, we will answer the question, “Does Sertraline increase GABA?”. We will discuss the interaction between Sertraline and the neurotransmitter, GABA. We will also discuss the factors that may influence the levels of GABA while on Sertraline, and what should one do if a Sertraline-induced change in GABA levels causes unwanted symptoms.

Does Sertraline increase GABA?

Sertraline may increase GABA levels in the brain. Sertraline primarily acts on the neurotransmitter serotonin but can also show very little activity on the gamma amino butyric acid (or γ-amino butyric acid) (GABA) levels as well.

Sertraline (also known as Zoloft) is a selective serotonin reuptake inhibitor (SSRI) approved by the FDA for the treatment of many depressive illnesses. It has also been used ‘off-label’ by healthcare professionals to manage premature ejaculation, binge eating disorder, bulimia nervosa (BN), generalised anxiety disorder (GAD) and body dysmorphic disorder (1,2).

GABA is a neurotransmitter in the brain which is responsible for the regulation and calming of neural activity. This neurotransmitter reduces excessive brain activity and promotes relaxation and improved sleep (3,4).

Does Sertraline affect GABA receptors in the brain?

Sertraline does not directly affect GABA receptors in the brain. This medication has the most activity of serotonin reuptake inhibition. However, very little affinity can be found for GABA receptors as well.

So if you are concerned about GABA and its interaction with Sertraline, it is advised to communicate your concerns to a healthcare professional.

What does research suggest?

Not much research has been conducted on the effects of Sertraline on GABA. However, the few studies that have been published report very little affinity of Sertraline with the GABA receptors.

A research study assessing the GABA concentrations in depressed individuals after being treated with SSRIs reported an increase in GABA concentrations in the occipital cortex of the brain after two months of treatment with the medications (5).

A study on women receiving Sertraline for premenstrual dysphoric disorder (PMDD), concluded that Sertraline can cause somewhat improvement in GABA-mediated effects (6).

Another research study examining the effects of Sertraline on the GABAergic neuroactive steroids in women taking Sertraline for PMDD stated a slight increase in the response of GABA-mediated neuroactive steroids (7).

What factors can influence GABA levels while on Sertraline?

If you are taking Sertraline, the following factors may influence GABA levels:

Factors Details
Dosage Higher doses of Sertraline may have a positive or negative impact on GABA neurotransmitter levels.
Duration Using Sertraline for a longer duration may increase the risk of a change in GABA levels.
Individual variability Each individual may react differently to Sertraline, which can influence the response of the medication to GABA and other neurotransmitters.
Brain chemistry Serotonin increased as a result of Sertraline use may indirectly affect GABA levels in the brain.
Medication interactions Psychotropic medications if given simultaneously with Sertraline can cause an interaction. Sometimes the interaction may also affect GABA receptors and concentrations.
Alcohol consumption Alcohol and coffee can affect Sertraline and GABA concentrations.
Underlying medical condition Mental health problems and anxiety issues, treated by Sertraline can change the levels of GABA in the brain.

What to do if Sertraline increases GABA levels?

Sertraline does not directly impact GABA concentrations within the brain. If you do feel any changes in mood or anxiety levels, and you suspect that this may be due to altered GABA levels with Sertraline use, you should seek medical guidance.

Your healthcare provider will diagnose the underlying cause of any symptoms, assess your situation and come up with a therapeutic regimen according to your needs. Your doctor may adjust the dosage of Sertraline, switch the time or withdraw the medication completely. Do not stop taking Sertraline without the advice of your healthcare provider.

If Sertraline increases or decreases GABA levels, there will changes in mood, anxiety and sedation levels. Cognitive impairment has also been associated with changes in GABA concentrations in the brain. If you experience any of these symptoms, you should keep a record and communicate with your doctor (8). 

Can other medications also affect GABA levels?

Other medications can also affect GABA levels. Using any of these medications concurrently with Sertraline can also cause a change In GABA levels. Some of these are as follows:

  • Benzodiazepines
  • Barbiturates
  • Neuroactive steroids
  • Inhalational anaesthetics
  • Intravenous anaesthetics
  • Other antidepressants (like Bupropion and Venlafaxine)

If you are using any such medication, please inform your healthcare provider so that any potential interactions or side effects can be avoided.

To the best of my knowledge, Sertraline does not significantly impact GABA levels in the brain. If you have any symptoms that you think may be due to Sertraline-induced GABAergic activity, you should seek medical advice.

In my opinion, each individual can respond differently to Sertraline and it may be rare but not impossible for Sertraline to cause significantly increased GABA levels. If you have concerns regarding this phenomenon you should communicate your concern to your healthcare provider for guidance.

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The Food and Drug Administration (FDA). HIGHLIGHTS OF PRESCRIBING INFORMATION. ZOLOFT® (sertraline hydrochloride) tablets, for oral use. Available from: 


Singh HK, Saadabadi A. Sertraline. [Updated 2023 Feb 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:


Allen MJ, Sabir S, Sharma S. GABA Receptor. [Updated 2023 Feb 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from:


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Sanacora G, Mason GF, Rothman DL, Krystal JH. Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. American Journal of Psychiatry. 2002 Apr 1;159(4):663-5.


Hantsoo L, Grillon C, Sammel M, Johnson R, Marks J, Epperson CN. Response to sertraline is associated with reduction in anxiety-potentiated startle in premenstrual dysphoric disorder. Psychopharmacology. 2021 Oct;238:2985-97.


Miller KN, Standeven L, Morrow AL, Payne JL, Epperson CN, Hantsoo L. GABAergic neuroactive steroid response to sertraline in premenstrual dysphoric disorder. Psychoneuroendocrinology. 2024 Feb 1;160:106684.


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