What other antidepressant can you take with sertraline? (3+ potential risks)

In this article, we will discuss the antidepressants you can safely take with sertraline. We will also discuss some research studies and how one can ensure the safe and effective use of sertraline with other antidepressants.

What other antidepressant can you take with sertraline?

Sertraline can be taken with the following antidepressants:

  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
  • Atypical antidepressants

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

SNRIs can be taken with sertraline, a selective serotonin reuptake inhibitor (SSRI). The combination of sertraline and a suitable SNRI can help manage the symptoms associated with treatment-resistant depression or major depressive disorder. (1)

SNRIs typically include:

  • Duloxetine (Cymbalta)
  • Venlafaxine (Effexor)
  • Desvenlafaxine (Pristiq)

SSRIs like sertraline work on serotonin levels and do not primarily affect other neurotransmitters such as norepinephrine and dopamine (2). SNRIs work on both serotonin and dopamine, making these meds cover broader symptoms. (1)

According to research studies, the combination of sertraline and venlafaxine is usually considered well-tolerated, and people usually respond well to it (3). However, these combinations can increase the risk of a rare but life-threatening condition called serotonin syndrome. 

This is because both sertraline and SNRIs work on serotonin levels. Dosage adjustment might be key to using these two classes of antidepressants together, but it still might not work for everyone. So, make sure you do not pair sertraline with SNRIs without consulting your healthcare provider.

Atypical antidepressants

Atypical antidepressants such as bupropion, mirtazapine, etc., can be used with sertraline. Research suggests that taking bupropion and sertraline together can offer a significant improvement in the symptoms of treatment-resistant depression and MDD (4). 

Furthermore, taking bupropion with sertraline can also prevent sertraline-induced sexual side effects and potential weight gain. 

This is because sertraline and bupropion have different mechanisms of action, and these meds can collectively manage serotonergic, dopaminergic, and noradrenergic systems in the brain (4). 

This also reduces the chance of serotonin syndrome to some extent, as bupropion does not primarily work on serotonin levels and focuses more on norepinephrine and dopamine.

Other atypical antidepressants, such as mirtazapine, can also be used with sertraline. Research suggests that mirtazapine and sertraline together can manage the symptoms of MDD and PTSD and improve the quality of life in such patients (5,6). 

Furthermore, mirtazapine, being a sedative antidepressant, can help with sertraline-induced insomnia, making falling asleep less difficult for such patients. 

This can also manage MDD comorbid with insomnia effectively. However, these medications are all prescription antidepressants and should not be taken without your doctor’s approval.

What are the potential risks of combining sertraline with other antidepressants?

The potential risks of combining sertraline with other antidepressants include:

Additive side effects

When combining sertraline with other antidepressants, there is a risk of experiencing additive side effects. The intensity of these side effects may be heightened when multiple medications are taken simultaneously. (7)

Antidepressant combinationCommon side effectsLess common side effects
Sertraline + SNRIsGI side effects, Insomnia, Headache, anxiety, irritation, mood changes, tiredness, dizziness, drowsiness, etcHeart palpitations, unusual mood changes, changes in blood pressure, memory issues, etc
Sertraline + BupropionInsomnia, nervousness, dry Mouth, GI side effects, dizziness, etc.Palpitations, blood pressure changes, increased risk of seizures, memory issues, etc.
Sertraline + MirtazapineGI side effects, weight gain, increased appetite, restlessness, tiredness, dizziness, etcMemory issues, heart palpitations, mood changes, increased sedation, etc.

GI (Gastrointestinal side effects typically include nausea, vomiting, diarrhoea, constipation, acid reflux, flatulence, bloating, abdominal pain, etc. 

Increased risk of serotonin syndrome

One significant concern is the potential for serotonin syndrome. Serotonin syndrome is a rare but serious condition that can occur when there is an excess of serotonin in the brain. 

Combining multiple antidepressants, especially those that increase serotonin levels, raises the risk of serotonin syndrome. Symptoms may include: (8)

  • Agitation or restlessness
  • Confusion
  • Rapid heart rate
  • Dilated pupils
  • Loss of muscle coordination or twitching muscles
  • Excessive sweating
  • Shivering or goosebumps
  • High blood pressure
  • Dilated pupils
  • Diarrhoea
  • Headache
  • High fever
  • Shivering or tremors
  • In severe cases, it can lead to seizures or unconsciousness.

Cardiovascular effects

The combination of sertraline with certain antidepressants may lead to cardiovascular side effects. These can manifest as palpitations, changes in blood pressure, or QTc prolongation, which is an alteration in the heart’s electrical activity. 

Increased seizure risk

Some antidepressants, notably bupropion, can lower the seizure threshold. When taken in combination with sertraline, there may be an increased risk of seizures. It’s essential to be cautious, especially in individuals with a history of seizures.

What antidepressants should not be taken with sertraline?

Antidepressants like monoamine oxidase inhibitors (MAOIs) and other serotonergic antidepressants such as escitalopram, citalopram, etc., should not be taken with sertraline.

This is because such combinations have higher risks of serotonin syndrome, and additive side effects might also be quite severe. MAOIs, in particular, inhibit the enzyme responsible for the metabolism or breakdown of excitatory chemicals, including serotonin. 

This dangerously increases serotonergic activity in the brain. Other SSRIs, since they work in the same way as sertraline, can also cause this complication with more pronounced inhibition of serotonin reuptake. So, these combinations should be avoided. 

Tricyclic antidepressants are also not commonly combined with sertraline due to the less safe side effect profile of TCAs.

How to ensure the safe use of sertraline with other antidepressants?

The following points are important to ensure the safe and effective use of sertraline with other antidepressants.

  • Before combining sertraline with other antidepressants, consult your doctor.
  • Stick to the prescribed dosages for each medication. Avoid self-adjusting doses or take these medications more often than directed.
  • Limit alcohol intake and avoid illicit substances, as these can interact with antidepressants and increase the risk of side effects.
  • Make sure that your doctor knows about all the other medications, both prescription and over-the-counter, that you are currently taking.
  • It is important to take your medications at the right time and space them out if advised. 
  • Understand the symptoms of serotonin syndrome, such as agitation, hallucinations, rapid heartbeat, and muscle stiffness. Seek immediate medical attention if these symptoms occur.

As a pharmacist, I always talk about the importance of sticking to the prescribed treatment regimen. If anything concerns you, just reach out to your provider. Do not try to make any changes to your prescription on your own.


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  1. Schneier FR, Campeas R, Carcamo J, Glass A, Lewis-Fernandez R, Neria Y, Sanchez-Lacay A, Vermes D, Wall MM. COMBINED MIRTAZAPINE AND SSRI TREATMENT OF PTSD: A PLACEBO-CONTROLLED TRIAL. Depress Anxiety. 2015 Aug;32(8):570-9. doi: 10.1002/da.22384. Epub 2015 Jun 26. PMID: 26115513; PMCID: PMC4515168. https://pubmed.ncbi.nlm.nih.gov/26115513/ 
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