Does sertraline increase dopamine? (3 factors involved)

In this article, we will discuss whether sertraline increases dopamine levels in the brain. We will also discuss some research studies and additional factors that can affect your dopamine levels while being treated with sertraline. 

Does sertraline increase dopamine?

Sertraline does not typically increase dopamine levels. It is a selective serotonin reuptake inhibitor that primarily increases serotonin levels by blocking serotonin transporters (SERT). (1,2)

This increases serotonergic activity in the brain, and as serotonin is primarily involved in the pathophysiology of depression, sertraline can manage symptoms of various mental health conditions. 

However, it selectively works on serotonin and is said to make little to no changes in dopaminergic and noradrenergic systems in the brain. Sertraline is also considered safe compared to other antidepressants because of its lesser affinity to bind to other receptors in the body, such as histamine and muscarinic receptors. 

However, some people may experience effects that are linked to increased dopamine while taking sertraline. If you’re concerned about the effects of sertraline or dopamine levels or you suspect something like this, please reach out to your healthcare provider to learn more.

What does research suggest?

There is limited research on the effects of sertraline on the dopaminergic system. However, existing research leans towards little to no activity of sertraline on dopamine levels. 

One research study explained the role of sertraline in the management of depression and indicated that clinical trials did not show a high affinity of sertraline for the dopaminergic and adrenergic systems in the brain (3). 

This implies that sertraline does not significantly affect or negligibly affect the levels of dopamine and norepinephrine, two other monoamine neurotransmitters besides serotonin (3). Other human studies have shown similar responses to sertraline.

However, animal studies suggest that sertraline may increase extracellular dopamine levels in the brain (4). 

Some animal studies have indicated that long-term use of antidepressants, including sertraline, can facilitate the dopaminergic system, and these effects are not typically observed after short-term use (5). 

Nevertheless, human studies do not show a marked effect of sertraline on dopamine levels. As the name of SSRIs indicates, they selectively work on serotonin levels.

What effects are linked to increased dopamine levels in the brain?

Increased dopamine levels can cause various benefits and side effects that may overlap with sertraline-induced benefits and side effects. These include: (6)

Beneficial effects

  • Improved mood
  • Enhanced focus and attention
  • Increased motivation
  • Pleasure and reward sensations
  • Enhanced cognitive function
  • Improved motor control

Side effects

  • Anxiety or restlessness
  • Insomnia
  • Impaired judgement
  • Increased heart rate and blood pressure
  • Agitation or irritability
  • Hallucinations (in rare cases)
  • Impulsivity
  • Seizures 

What additional factors can influence dopamine while taking sertraline?

Some additional factors can influence dopamine while taking sertraline, including:

Underlying health conditions

Pre-existing health conditions, such as neurological disorders or conditions affecting dopamine regulation, can impact dopamine levels in conjunction with sertraline use.

Use of other medications

Concurrent use of medications that influence dopamine levels independently of sertraline may contribute to variations in dopamine. It’s essential to consider the potential interactions between sertraline and other medications. The medications that affect dopamine levels include: (7)

Medication ClassExamplesMechanism of Action
Dopamine AgonistsPramipexole, RopiniroleMimic the action of dopamine in the brain.
Levodopa/Carbidopa (for Parkinson’s)Sinemet (levodopa/carbidopa)Increases dopamine levels in the brain.
MAO-B Inhibitors (for Parkinson’s)Rasagiline, SelegilineIncrease dopamine levels by inhibiting its breakdown.
Methylphenidate and AmphetaminesRitalin, AdderallIncrease dopamine and norepinephrine release.
Selective Dopamine Reuptake Inhibitors (SDRIs)BupropionInhibits the reuptake of dopamine and norepinephrine.
CocaineBlocks the reuptake of dopamine, leading to increased levels.
NicotineStimulates dopamine release in the brain.

Stress levels

High stress levels can affect dopamine regulation. Strategies to manage stress, such as relaxation techniques and mindfulness, may help mitigate potential fluctuations in dopamine.

What to do if you’re concerned about increased dopamine levels?

If you’re concerned about increased dopamine levels while taking sertraline, please reach out to your provider. It is highly unlikely for sertraline to affect your dopamine levels independently. 

However, if you’re taking another antidepressant with it or any other medication that can potentially affect your dopamine levels, your doctor will readjust your treatment plan. Your healthcare team will also check for other factors that could be contributing to these effects. 

However, sertraline itself cannot increase dopamine to a level where you actually start feeling it. If you keep experiencing unusual effects while on sertraline, it might indicate that sertraline is not the best choice of antidepressant for you. 

In that case, your doctor will consider alternative treatment options to target your symptoms more accurately. However, make sure you do not make any changes to your prescription on your own. Sertraline does not work right away so one should give it enough time to kick in.

The link between dopamine and sertraline

In my experience as a pharmacist, I have never seen a case of sertraline-induced high dopamine levels. Most beneficial effects or side effects of sertraline are linked to increased serotonergic activity in the brain because that’s how this antidepressant primarily works. 

However, I do remember a case of increased dopamine levels and related complications in a patient taking sertraline while abusing cocaine. So it’s safe to say that cocaine had a lot more to do with dopamine levels than sertraline. 

However, increased serotonergic and dopaminergic activity in the brain collectively led to disturbing complications. So, it is important to ensure that you’re taking all your prescription meds properly and that you do not have any other factors affecting your dopamine levels. 

If you need to learn more about how sertraline works, what chemicals it acts on, and how it is all linked with your current symptoms, you can reach out to your healthcare provider.

References 

  1. Singh HK, Saadabadi A. Sertraline. 2023 Feb 13. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 31613469. Available from: https://www.ncbi.nlm.nih.gov/books/NBK547689 
  1. The Food and Drug Administration (FDA). HIGHLIGHTS OF PRESCRIBING INFORMATION. ZOLOFT (sertraline hydrochloride) tablets, for oral use. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/019839s74s86s87_20990s35s44s45lbl.pdf
  1. Shelton RC. The role of sertraline in the management of depression. Clin Ther. 1994 Sep-Oct;16(5):768-82; discussion 767. PMID: 7859236. https://pubmed.ncbi.nlm.nih.gov/7859236/#:~:text=Sertraline%20is%20a%20highly%20specific,%2C%20dopaminergic%2C%20and%20adrenergic%20receptors 
  1. Kitaichi Y, Inoue T, Nakagawa S, Boku S, Kakuta A, Izumi T, Koyama T. Sertraline increases extracellular levels not only of serotonin, but also of dopamine in the nucleus accumbens and striatum of rats. Eur J Pharmacol. 2010 Nov 25;647(1-3):90-6. doi: 10.1016/j.ejphar.2010.08.026. Epub 2010 Sep 9. PMID: 20816814. https://pubmed.ncbi.nlm.nih.gov/20816814/ 
  1. Huzarska M, Zieliński M, Herman ZS. Repeated treatment with antidepressants enhances dopamine D1 receptor gene expression in the rat brain. Eur J Pharmacol. 2006 Feb 27;532(3):208-13. doi: 10.1016/j.ejphar.2005.09.069. PMID: 16499906. https://pubmed.ncbi.nlm.nih.gov/16499906/ 
  1. PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 681, Dopamine; [cited 2024 Jan. 10]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Dopamine 
  1. Velasco M, Luchsinger A. Dopamine: pharmacologic and therapeutic aspects. Am J Ther. 1998 Jan;5(1):37-43. PMID: 10099036. https://pubmed.ncbi.nlm.nih.gov/10099036/ 

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