What Is the Relationship between Sertraline and Dopamine?

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  • Written By: Christina Hall
  • Edited By: Lauren Fritsky
  • Last Modified Date: 31 March 2020
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The relationship between sertraline and dopamine lies in the unique action that the selective serotonin reuptake inhibitor (SSRI) has on the dopamine pathway. Sertraline possesses the ability to partially block dopamine reuptake pumps. When dopamine pumps become blocked, more dopamine is left to circulate in the synaptic cleft, leading to increased neurotransmission and action. These two substances are often thought of together in psychiatry because sertraline is the only known SSRI that has a significant impact on the dopamine pathway. This additional ability to interact with dopamine is thought to account for the drug’s efficacy and unique effect on depression and other mental illnesses.


Sertraline and dopamine pathways cross in a number of different areas of the brain, which initiates the drug’s common motivational and energetic effects on the patient. While receptors for serotonin, the target neurotransmitter for most antidepressant drugs, are found abundantly throughout the brain, the majority of dopamine receptors are located in specific areas close to the brainstem. One area where the receptors are found is the mesolimbic pathway, which is known to be significantly important for the experience of pleasure, joy, and reward and also for adequate motivation to complete activities of daily living. The dopamine action prompted by sertraline in this area is thought to contribute to its positive effect on depression, anxiety, and many related disorders. The specificity of dopamine-active areas of the brain has led to sertraline and dopamine affinity being studied by those engineering the new class of antidepressant medication.

The paths of sertraline and dopamine cross in an area called the nigrostriatal pathway as well. Here, increased dopamine in the synaptic cleft may help a patient to plan more efficiently, decreasing anxiety, and increased dopamine activity increases cognition, which can lead to the patient experiencing a higher sense of fulfillment and interest in life activities. Interaction between these two substances is also seen in the thalamus, an area which is important to the transfer of information throughout the whole body. In light of this research, it has become easier for clinicians to understand the role that dopamine dysregulation plays in mental illnesses like schizophrenia and attention-deficit disorder, diseases in which smooth information transfer is inhibited.

Anhedonia, a serious symptom of depression that is characterized by an absolute inability to feel pleasure, can be mitigated, in some cases, with drugs that increase dopamine availability. The well-researched link between sertraline and dopamine has led to success in using the SSRI for off-label uses, like for the treatment of generalized anxiety disorder (GAD). The sertraline and dopamine link has led many clinicians in the field to recognize the probability that serotonin is not solely responsible for diseases like major depressive and bipolar disorder.


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Post 3

Most people consider sertraline's effect on dopamine as a good thing. But I read a doctor's report recently in which the doctor felt that the dopamine increasing effects of sertraline may rarely lead to psychosis. He only based this on the observation of one patient though which is obviously far from definitive proof. But if it has happened to someone, I think it's possible that it may happen to others.

This patient was on sertraline 200mg for some time when she started experience psychosis symptoms like suspicion and hallucination. The symptoms completely resolved after she was taken off of the medication.

Post 2

This is interesting. I've used sertraline in the past but I had no idea about the relationship with dopamine. I always assumed that the medication worked on serotonin alone like all SSRIs. I guess sertraline is unique in this sense. I read recently that sertraline is the most commonly prescribed antidepressant in America as of 2013. It obviously works well, that's why doctors prefer it.

Post 1

My doctor put me on sertraline recently for depression. I went to see him because I have been experiencing low moods and anxiety frequently for some months. I feel down most of the time and I never feel like doing anything. I get myself to work but remain at home at other times. I've stopped even my regular activities that I used to enjoy. I realized it was time to see the doctor when my roommate commented on how sad and depressed I look lately.

It has been only a few weeks on the drug, but I have been feeling better. I took a walk this morning and even made cookies. I think these are signs that I'm feeling better. There was no way I would do either a few weeks ago. It must be sertraline's effect on dopamine levels. Hopefully I'll be my old self again soon.

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