Is sertraline sedating or activating? (3 research studies)

In this article, we will discuss whether sertraline is sedating or activating. We will also talk about some research studies and what factors can affect the effects of sertraline. We will also discuss some management tips. 

Is sertraline sedating or activating?

Sertraline (Zoloft) can be both sedating and activating, depending on the individual taking the medication. Sertraline is a selective serotonin reuptake inhibitor primarily used as an antidepressant (1,2).

Drowsiness and insomnia are both listed as potential side effects of this antidepressant, indicating that sertraline can have both sedating and activating effects (3). It’s important to note that people are different and can respond differently to medications like sertraline. 

Additionally, individuals may experience different symptoms of depression or anxiety that sertraline treats. This antidepressant works by balancing the amount of serotonin in the brain, which is an excitatory neurotransmitter. This can lead to various responses.

People who may feel drowsy due to depression may begin to feel more energetic as sertraline takes effect, as the antidepressant helps manage their depression. If depression causes insomnia or sleep disturbances, taking sertraline can help manage that, helping your sleep patterns return to normal. 

So, it completely depends on the person and their current symptoms, and sertraline can cause different side effects in different individuals.

What does research suggest?

Several research studies have discussed the effects of sertraline on energy levels and sleep architecture. Insomnia is listed as one of the reported side effects of sertraline and related SSRIs (3). 

One research study indicated that sertraline can affect rapid eye movement (REM) periods in people with major depressive disorder (4). Some research studies have suggested that sertraline can trigger fatigue and sleepiness in some individuals being treated with this antidepressant (5). 

However, people with underlying conditions, like renal diseases, may be more susceptible to this. Nevertheless, some researchers have explained how sertraline is a good and sometimes unavoidable option in cases of depression comorbid with fatigue (6). 

These studies show how sertraline can be both sedating or activating, depending on the individual taking this antidepressant, their current symptoms, and any underlying health condition they might have.

What factors can affect the sedative or activating effects of sertraline?

Several factors can affect the sedative or activating effects of sertraline, including:

  • Individual responses to sertraline can vary widely. While some may experience sedative effects, others might feel activated. 
  • The nature and severity of depression symptoms can influence whether sertraline has a more sedative or activating impact. Individuals with fatigue may find sertraline activating, whereas those with insomnia and anxiety might experience a calming influence.
  • Other existing health conditions play a role in determining the sedative or activating effects of sertraline.
  • Concurrent use of other medications can interact with sertraline’s effects. Medications with sedative properties, when taken with sertraline, may enhance the sedative effects, while stimulant medications might contribute to increased activation. 
  • The dosage of Zoloft prescribed can also contribute to its sedative or activating effects. 

What to do if you are concerned about the effects of sertraline?

If you are concerned about the sedating or activating effects of sertraline, please reach out to your healthcare provider. Your doctor will properly monitor your symptoms and adjust your treatment plan accordingly. 

If you are experiencing more enhanced sedating or activating effects of sertraline after a recent dose escalation, reducing the dose is a common approach to manage these side effects. Dose reduction does help in the majority of cases and can help provide relief. 

However, sertraline may continue to cause side effects in some people. If you find it difficult to tolerate this antidepressant, your doctor will consider alternative treatment options.

What are the alternatives to sertraline if it causes sedation or activation?

There are many alternatives to sertraline if it is causing sedative or activating effects. If it is causing excess sedation or affecting your daytime mental alertness, there are some sedative antidepressants, such as Wellbutrin, that can replace sertraline. 

Wellbutrin is considered the best antidepressant for energy and motivation. This antidepressant is widely used and can help increase your energy levels throughout the day if you find sertraline too sedative. 

If sertraline is causing activating effects, there are sedative antidepressants, such as mirtazapine and trazodone, which can help you sleep while controlling your depression. 

There are also a bunch of other antidepressants, including SSRIs and SNRIs, that are neither considered sedative nor activating. These meds can also affect people differently. 

The most important thing to note here is that you should always rely on your doctor’s expertise to determine the best alternative treatment strategy for your symptoms. Do not try to make any changes to your prescription on your own.


  1. Singh HK, Saadabadi A. Sertraline. 2023 Feb 13. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 31613469. Available from:
  1. The Food and Drug Administration (FDA). HIGHLIGHTS OF PRESCRIBING INFORMATION. ZOLOFT (sertraline hydrochloride) tablets, for oral use. Available from:
  1. National Library of Medicine. Sertraline: MedlinePlus Drug Information [Internet]. Bethesda (MD): U.S. National Library of Medicine. Available from:
  1. Jindal RD, Friedman ES, Berman SR, Fasiczka AL, Howland RH, Thase ME. Effects of sertraline on sleep architecture in patients with depression. J Clin Psychopharmacol. 2003 Dec;23(6):540-8. doi: 10.1097/ PMID: 14624183. 
  1. Chien CW, Tai YM, Chen CY, Chu P, Tzeng NS. Sertraline-Induced Neutropenia and Fatigue in a Patient With End-Stage Renal Disease. Am J Ther. 2020 May 5;29(1):e101-e103. doi: 10.1097/MJT.0000000000001192. PMID: 32384314. 
  1. Marin H, Menza MA. Specific treatment of residual fatigue in depressed patients. Psychiatry (Edgmont). 2004 Sep;1(2):12-8. PMID: 21197374; PMCID: PMC3012615. 

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