What is a good antidepressant to take with Wellbutrin? (5+ good options)

In this article, we will discuss what antidepressants are safe to take with Wellbutrin – an atypical antidepressant. We will also discuss some research studies and the potential risks of such combinations. 

What is a good antidepressant to take with Wellbutrin?

The following antidepressants are considered good to combine with Wellbutrin (bupropion), including:

  • Selective Serotonin Reuptake Inhibitors (SSRIs)
  • Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs are the most commonly prescribed antidepressants and are considered good options to pair with Wellbutrin. SSRIs typically include: (1)

  • Fluoxetine (Prozac)
  • Escitalopram (Lexapro)
  • Sertraline (Zoloft)
  • Paroxetine (Paxil)
  • Citalopram (Celexa)
  • Fluvoxamine (Luvox)

These medications can be safely taken with Wellbutrin because of how they work. Antidepressant combinations, in general, can be tricky due to their mechanisms of action. The primary concern with SSRI combinations is serotonin syndrome. 

SSRIs primarily work by inhibiting the reuptake of serotonin through the blocking of serotonin transporters (SERT). As serotonin is heavily involved in the pathophysiology of depression and related symptoms, SSRIs can actively control these mental health conditions (1). 

However, the major concern with using SSRIs in combination with another antidepressant is too much serotonergic activity, which can do more harm than good. 

This is where antidepressants like Wellbutrin can be beneficial to pair with SSRIs because Wellbutrin primarily works on noradrenaline and dopamine levels, not serotonin (2). 

This mechanism of Wellbutrin makes it a good match with SSRIs, as this combination does not dangerously increase serotonin levels in the body. However, it is important to note that taking SSRIs with Wellbutrin can cause side effects in some individuals, and this combination might not be the best option for everyone.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs):

SNRIs are also commonly used for the management of depression and are considered good options to take with Wellbutrin. SNRIs typically include: (3)

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

SNRIs, unlike SSRIs, work on both serotonin and norepinephrine levels. Since only one class of antidepressants works on serotonin in this case, the chances of serotonin syndrome are not as high as in the case of two serotonergic antidepressants being used together. 

However, it is important to note that this combination might cause side effects in susceptible individuals and should not be taken unless prescribed by a qualified healthcare professional.

What does research suggest?

Several research studies have indicated that combining Wellbutrin with SSRIs or SNRIs can be beneficial for people who experience treatment-resistant depression. 

Severe depression or major depressive disorder (MDD) does not respond well to antidepressant monotherapy. This is where antidepressant combinations can be effective. 

One research study indicated that bupropion, the active drug in Wellbutrin, when paired with an SSRI or SNRI, can actively manage symptoms associated with MDD (4). The study also showed that bupropion can mitigate the sexual disturbances associated with SSRIs and SNRIs. 

Another research study monitored the effects of bupropion combined with escitalopram (an SSRI) to manage treatment-resistant depression (5). The study indicated that this combination showed a significant response compared to escitalopram monotherapy.

What are the potential side effects of taking Wellbutrin with SSRIs or SNRIs?

Taking Wellbutrin with SSRIs or SNRIs can cause some side effects, including: (1,2,3)

Additive side effects

  • Nausea
  • Insomnia
  • Headache
  • Dry mouth
  • Increased heart rate
  • Agitation
  • Anxiety
  • Constipation 
  • Tiredness
  • Weakness 

Serious side effects

  • Seizures (especially at higher doses)
  • Hypertension (high blood pressure)
  • Allergic reactions
  • QTc prolongation
  • Serotonin syndrome 

These side effects can vary from person to person and may depend on the dosage strength taken. If you are taking this combination and feel unusual, please reach out to your healthcare provider.

What are the typical dosage recommendations for Wellbutrin (bupropion)?

The typical dosage recommendations for Wellbutrin include: (2)

Dosage formsConditionsDosage recommendations
Wellbutrin Depression100mg once daily starting dose. Should not exceed 450mg per day.
Wellbutrin XL (extended-release tablets)Depression150mg once daily starting dose. Should not exceed 450mg per day.
Seasonal affective disorder150mg once daily starting dose. Should not exceed 300mg per day.
Wellbutrin SR (sustained-release tablets) Only used for major depressive disorder (MDD)150mg once daily starting dose. Should not exceed 200mg two times a day.

The above-mentioned doses are for adults. For children, the dose must be determined by a healthcare provider based on age, weight, and the severity of symptoms. 

How to ensure the safe and effective use of Wellbutrin with another antidepressant?

The following points are important to ensure the safe and effective use of Wellbutrin with another antidepressant:

  • Before combining medications, consult with a healthcare provider.
  • If combining Wellbutrin with another antidepressant, the doses may need adjustment. Your healthcare provider will determine the appropriate dosage for each medication to minimise the risk of side effects.
  • Look out for any side effects or adverse reactions. Notify your healthcare provider immediately if you experience unusual symptoms or discomfort.
  • Follow the prescribed timing for each medication. 
  • Limit or avoid alcohol and other substances that may interact with antidepressants, as they can exacerbate side effects and compromise treatment effectiveness.
  • Be aware of the symptoms of serotonin syndrome, a rare but potentially serious condition that can occur when combining certain antidepressants.

As a pharmacist, I always ask my patients to keep a close eye on their side effects when taking a combination of antidepressants. These medications might not be well-tolerated in every case and sticking to the prescribed doses is crucial to ensure the safety and efficacy of your treatment. 


  1. Chu A, Wadhwa R. Selective Serotonin Reuptake Inhibitors. 2023 May 1. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 32119293. https://www.ncbi.nlm.nih.gov/books/NBK554406 
  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 
  1. Sansone RA, Sansone LA. Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison. Innov Clin Neurosci. 2014 Mar;11(3-4):37-42. PMID: 24800132; PMCID: PMC4008300. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4008300/ 
  1. Zisook S, Rush AJ, Haight BR, Clines DC, Rockett CB. Use of bupropion in combination with serotonin reuptake inhibitors. Biol Psychiatry. 2006 Feb 1;59(3):203-10. doi: 10.1016/j.biopsych.2005.06.027. Epub 2005 Sep 13. PMID: 16165100. https://pubmed.ncbi.nlm.nih.gov/16165100/ 
  1. Leuchter AF, Lesser IM, Trivedi MH, Rush AJ, Morris DW, Warden D, Fava M, Wisniewski SR, Luther JF, Perales M, Gaynes BN, Stewart JW. An open pilot study of the combination of escitalopram and bupropion-SR for outpatients with major depressive disorder. J Psychiatr Pract. 2008 Sep;14(5):271-80. doi: 10.1097/01.pra.0000336754.19566.65. PMID: 18832958; PMCID: PMC2778329. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778329/ 

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