What is a good antidepressant to take with Lexapro? (1+ benefits)

In this article, we will discuss what antidepressant is a good option to combine with Lexapro (escitalopram), a selective serotonin reuptake inhibitor. We will also discuss some potential benefits and risks of combining Lexapro with another antidepressant and how one can ensure safe use.

What is a good antidepressant to take with Lexapro?

Wellbutrin (bupropion) is considered a good antidepressant to take with Lexapro (escitalopram) because of how it works. The major concern with antidepressant combinations is the risk of increased side effects and serotonin syndrome – a condition associated with too much serotonergic activity in the brain (1). 

Wellbutrin is considered a good option because it’s an atypical antidepressant that does not work the way Lexapro does – a selective serotonin reuptake inhibitor (SSRI). (2)

Lexapro is the most selective SSRI, causing the most inhibition of serotonin reuptake compared to other members of this class (3). It does not affect other neurotransmitters enough to create a clinically significant response. 

This primary effect of Lexapro on serotonin makes it unsuitable to pair with other medications that can also increase serotonin levels, such as other SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), and serotonergic antidepressants like trazodone. 

The effects of Wellbutrin on serotonin are minimal, as it primarily acts on two other monoamine neurotransmitters – norepinephrine and dopamine. It is sometimes also known as a norepinephrine and dopamine reuptake inhibitor (NDRI). (4)

In fact, Wellbutrin is the only NDRI approved in the US to treat depression. This mechanism of action makes Wellbutrin a good option to be combined with serotonergic antidepressants like Lexapro. These meds can together work on three excitatory chemicals involved in the pathophysiology of depression.

What are the benefits of taking Lexapro with a compatible antidepressant?

Taking Lexapro with a suitable antidepressant can offer the following potential benefits: (2,4)

Treatment of major depressive disorder (MDD)

Using a single antidepressant may not always effectively manage major depressive disorder. Combining Lexapro with a compatible antidepressant enhances the overall treatment approach, helping MDD in a better way.

Reduced Lexapro-induced side effects

Pairing Lexapro with a suitable antidepressant can mitigate specific side effects associated with Lexapro use, such as Lexapro-induced sexual disturbances or weight gain. Taking Lexapro with a low-dose sedative antidepressant can manage insomnia associated with this SSRI.

What are the side effects of taking Lexapro with another antidepressant?

Taking Lexapro with another antidepressant like Wellbutrin can cause the following side effects: (2,4)

Additive side effects

When taking two compatible antidepressants together, there’s a possibility of experiencing additive side effects. These can include: 

  • early anxiety
  • sleeping issues
  • Tiredness
  • Nausea
  • Vomiting
  • disturbed stomach
  • diarrhoea or constipation
  • dry mouth. 

While these side effects are common with many antidepressants individually, their occurrence may intensify when the medications are used in combination.

Risk of serotonin syndrome

Serotonin syndrome is a rare but potentially serious condition that is triggered by too much serotonergic activity in the brain. Since Lexapro primarily affects serotonin levels, combining it with another antidepressant that also affects serotonin levels may increase the risk of serotonin syndrome. 

However, it’s crucial to note that the likelihood of this side effect is dose-dependent, with higher doses increasing the chances.

Some signs and symptoms associated with serotonin syndrome are: (1)

  • 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.

Risk of seizures

Certain antidepressants, such as Wellbutrin, carry a rare risk of causing seizures. Lexapro, while generally considered low-risk for seizures, may lower the seizure threshold in some cases. 

Combining these medications could potentially increase the risk of convulsions, especially in individuals who are susceptible to seizures.

What antidepressants should not be taken with Lexapro?

The following antidepressants should be avoided with Lexapro: 

Other Selective Serotonin Reuptake Inhibitors (SSRIs)

Using Lexapro with other SSRIs can increase the risk of serotonin syndrome. Since these medications have similar side effect profiles and both work on serotonin levels, combining them may lead to potentially dangerous additive side effects.

Tricyclic Antidepressants (TCAs)

The combination of Lexapro with TCAs may result in a less favourable side effect profile. TCAs often have more side effects compared to newer antidepressants, and combining them with Lexapro could intensify the overall adverse effects.

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs should never be paired with Lexapro. MAOIs inhibit enzymes responsible for breaking down neurotransmitters like serotonin. When taken together, the levels of serotonin can increase dangerously, leading to serotonin syndrome – a potentially life-threatening condition.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

Similar to SSRIs, combining Lexapro with SNRIs may not be preferred due to the risk of serotonin syndrome. SNRIs also affect serotonin levels, and the additive effects of both medications could be more pronounced.

How to ensure the safe use of Lexapro with another antidepressant?

The following points are important to ensure the safe and effective use of Lexapro and another compatible antidepressant, such as Wellbutrin:

  • Stick to the recommended doses. Exceeding doses can increase the risk of side effects and potentially lead to serotonin syndrome.
  • Regular monitoring of side effects is important as even compatible antidepressants may cause adverse reactions. Report any unusual symptoms or discomfort to your provider.
  • Follow the recommended timing and spacing of the two antidepressants.
  • Make sure you inform your doctor about all the medications you are taking, including OTC meds.
  • Alcohol should be avoided while taking antidepressants, including Lexapro. Alcohol can negatively impact mental and physical health, and its interaction with antidepressants may exacerbate side effects or reduce the effectiveness of the medication.

As a pharmacist, I always help my patients understand how important it is to ensure the safe and effective use of antidepressant combinations. You strictly have to stick to the recommended doses to prevent side effects or any other complications. 

It is also important to note that antidepressants are prescription medications and should never be combined without your doctor’s approval. 


  1. Simon LV, Keenaghan M. Serotonin Syndrome. 2023 Jul 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 29493999. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482377
  1. Landy K, Rosani A, Estevez R. Escitalopram. 2023 Nov 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 32491666. https://www.ncbi.nlm.nih.gov/books/NBK557734 
  1. Kennedy SH, Andersen HF, Lam RW. Efficacy of escitalopram in the treatment of major depressive disorder compared with conventional selective serotonin reuptake inhibitors and venlafaxine XR: a meta-analysis. J Psychiatry Neurosci. 2006 Mar;31(2):122-31. Erratum in: J Psychiatry Neurosci. 2006 Jul;31(4):228. PMID: 16575428; PMCID: PMC1413963. https://pubmed.ncbi.nlm.nih.gov/16575428/ 
  1. Huecker MR, Smiley A, Saadabadi A. Bupropion. 2023 Apr 9. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 29262173. https://www.ncbi.nlm.nih.gov/books/NBK470212 

Was this helpful?

Thanks for your feedback!