Is Wellbutrin an SSRI? Understanding the Differences and Uses

Off-label uses of Wellbutrin often mirror SSRI prescribing patterns and include treatment for anxiety disorders, ADHD, and smoking cessation. However, it’s worth noting that while SSRIs are typically first-line treatments for anxiety disorders, Wellbutrin may sometimes increase anxiety in certain patients, particularly when treatment is initiated or doses are adjusted.

Multiple studies have demonstrated that Wellbutrin is equally effective as SSRIs for treating depression [5][11]. However, its unique mechanism makes it particularly effective for people with melancholic depression, a subtype characterized by severe symptoms including loss of pleasure, significant weight loss, and profound sadness, or those who have experienced SSRI-related side effects. It has also been shown to be helpful as an augmentation therapy, and can be combined with SSRIs to enhance antidepressant effects and reduce sexual side effects [2][4][10].# Is Wellbutrin an SSRI? Understanding the Differences and Uses

Is Wellbutrin an SSRI? It’s a common question for those exploring treatment options for depression or other mental health conditions. The short answer is no, Wellbutrin is not an SSRI. It belongs to a unique class of antidepressants with a different mechanism of action, side effect profile, and clinical utility that sets it apart from traditional selective serotonin reuptake inhibitors.

What Is Wellbutrin and How Does It Work?

Wellbutrin, known generically as bupropion, is classified as a norepinephrine-dopamine reuptake inhibitor (NDRI). This medication works by inhibiting the reuptake of two key neurotransmitters in the brain, dopamine and norepinephrine, which play important roles in regulating mood, energy, attention, and motivation [7][9]. Unlike SSRIs, which target serotonin, bupropion’s dopaminergic and noradrenergic effects can offer distinct therapeutic benefits for those suffering from depression.

The drug is available in several formulations, including Wellbutrin SR (sustained-release) and Wellbutrin XL (extended-release), which allow for different dosing schedules to accommodate patient needs and preferences. Wellbutrin is FDA-approved for the treatment of major depressive disorder (MDD) and seasonal affective disorder (SAD). Under the brand name Zyban, it is also used for smoking cessation [3]. Off-label, bupropion is prescribed for attention-deficit/hyperactivity disorder (ADHD) and for lessening sexual side effects caused by SSRIs.

Wellbutrin vs SSRIs: What’s the Real Difference?

Understanding the fundamental differences between Wellbutrin and SSRIs requires examining how each drug class affects neurotransmitters and mood regulation in the brain.

How Wellbutrin’s Mechanism Differs from SSRIs

SSRIs, or selective serotonin reuptake inhibitors, including sertraline (Zoloft), fluoxetine (Prozac), and citalopram (Celexa), function by increasing serotonin levels in the brain, which is believed to help regulate mood, anxiety, and appetite. The “selective” nature of these medications means they primarily target serotonin pathways.

Bupropion, in contrast, does not affect serotonin directly. Instead, it boosts dopamine and norepinephrine, which are more directly associated with alertness, pleasure, and motivation [6]. This fundamental difference in antidepressant mechanism explains why Wellbutrin often produces different therapeutic effects and side effect profiles compared to SSRIs.

Comparing Wellbutrin to Lexapro and Zoloft

When comparing Wellbutrin to popular SSRIs like Lexapro (escitalopram) and Zoloft (sertraline), several key differences emerge:

Energy and Motivation: Wellbutrin is often prescribed for individuals who experience low energy, lack of motivation, or fatigue, symptoms not always effectively addressed by SSRIs. In fact, some SSRIs can sometimes contribute to feelings of emotional blunting or decreased energy.

Sexual Side Effects: One of the most significant advantages of Wellbutrin is that it lacks many of the sexual side effects frequently associated with SSRIs, making it an appealing option for patients who have experienced SSRI-related sexual dysfunction [1].

Weight Effects: While many SSRIs can cause weight gain, Wellbutrin is more likely to be weight-neutral or even associated with modest weight loss, which can be beneficial for some patients.

Is Wellbutrin Used Like an SSRI?

Despite its different mechanism of action, Wellbutrin is often used in similar clinical scenarios as SSRIs, though with some important distinctions.

FDA-approved uses for Wellbutrin include major depressive disorder (MDD) and seasonal affective disorder (SAD). These are conditions commonly treated with SSRIs as well, making Wellbutrin an alternative first-line treatment option.

Off-label uses of Wellbutrin often mirror SSRI prescribing patterns and include treatment for anxiety disorders, ADHD, and smoking cessation. However, it’s worth noting that while SSRIs are typically first-line treatments for anxiety disorders, Wellbutrin may sometimes increase anxiety in certain patients, particularly when treatment is initiated or doses are adjusted.

Multiple studies have demonstrated that Wellbutrin is equally effective as SSRIs for treating depression. However, its unique mechanism makes it particularly effective for people with melancholic depression, a subtype characterized by severe symptoms including loss of pleasure, significant weight loss, and profound sadness, or those who have experienced SSRI-related side effects.

Side Effects: How Wellbutrin Compares to SSRIs

Understanding the side effect profiles of these medications is crucial for patients and healthcare providers making treatment decisions.

Wellbutrin Side Effects

Although Wellbutrin is generally well-tolerated, it carries some unique risks and adverse effects:

• Seizure Risk: The most notable concern is the potential for seizures, which is dose-dependent and more likely in individuals with a history of seizures, eating disorders, or head trauma [3]
• Insomnia: Many patients experience difficulty sleeping, especially if doses are taken later in the day
• Dry Mouth and Headaches: Common but generally manageable side effects
• Increased Anxiety: Some patients may experience heightened anxiety, particularly during the initial weeks of treatment [13]

SSRI Side Effects

SSRIs have their own characteristic side effect profile:

• Sexual Dysfunction: Including decreased libido, difficulty achieving orgasm, and erectile dysfunction
• Weight Gain: Often gradual but can be significant for some patients
• Emotional Blunting: Some patients report feeling less emotionally reactive or “numb”
• Gastrointestinal Issues: Including nausea, diarrhea, and stomach upset
• Withdrawal Symptoms: Can occur when discontinuing treatment

Compared to SSRIs, bupropion is less likely to cause sexual dysfunction, weight gain, or emotional blunting [1], which often makes it a preferred option for individuals sensitive to these particular side effects.

Who Should Use Caution with Wellbutrin?

• Those with a history of seizures or seizure disorders, recent head injury or brain trauma [ [3]
• Individuals with current or past history of eating disorders (e.g., anorexia nervosa, bulimia) [3]
• Individuals undergoing abrupt cessation of alcohol, benzodiazepines, sedatives, or anticonvulsant medications [3]

Can You Take Wellbutrin With an SSRI?

Yes, Wellbutrin is often combined with SSRIs in clinical practice, a strategy known as augmentation therapy. This combination approach is particularly valuable when:

• An SSRI alone provides insufficient symptom relief
• Patients experience unwanted SSRI side effects, particularly sexual dysfunction
• Healthcare providers want to target multiple neurotransmitter systems for enhanced therapeutic effect

The two medications complement each other pharmacologically, with Wellbutrin’s energizing effect balancing the calming effect of SSRIs [2]. This combination can be particularly effective for patients with treatment-resistant depression or those who need comprehensive symptom management.

However, combination therapy requires close monitoring by a healthcare provider due to increased risk of side effects, including:

• Drug interactions that could affect medication metabolism
• Increased seizure risk from Wellbutrin [3]
• Potential for serotonin syndrome, though this is rare with this particular combination

When properly managed, this combination therapy can significantly improve treatment outcomes for many patients who don’t respond adequately to monotherapy [14].

Final Answer: Is Wellbutrin an SSRI?

No, Wellbutrin is definitively not an SSRI. It belongs to a distinct class of antidepressants called norepinephrine-dopamine reuptake inhibitors (NDRIs). While both Wellbutrin and SSRIs are used to treat depression and other mental health conditions, they work through completely different mechanisms and offer different therapeutic advantages.

Wellbutrin may be preferred when:

• Patients have experienced sexual side effects from SSRIs
• Energy and motivation are primary concerns
• Weight gain from other antidepressants is problematic
• Patients have comorbid ADHD symptoms
• Smoking cessation support is needed

The choice between Wellbutrin and SSRIs should always be made in consultation with a qualified healthcare provider who can assess individual symptoms, medical history, and treatment goals.

Take Control of Your Mental Health Journey

You don’t have to navigate depression, anxiety, or other mental health challenges alone. Whether you’re considering Wellbutrin, SSRIs, or exploring your treatment options for the first time, professional guidance is essential for finding the right approach for your unique situation.

Online psychiatric care from PsychPlus makes it easier to access expert mental health treatment. Our board-certified providers understand the nuances of different antidepressant medications and will work with you to develop a personalized treatment plan that addresses your specific symptoms and concerns. With both in-person and virtual appointments available, you can receive comprehensive psychiatric care on your schedule, from the comfort of your home.

Still unsure which antidepressant is right for you? PsychPlus offers expert guidance and custom treatment plans tailored to your individual needs. Get Started with PsychPlus →

References

1. Clayton, A. H., Keller, A., & McGarvey, E. L. (2006). Burden of phase-specific sexual dysfunction with SSRIs and a potential role for bupropion. Expert Opinion on Pharmacotherapy, 7(10), 1375–1389. https://pubmed.ncbi.nlm.nih.gov/25148932/
2. Fava, M., & Targum, S. D. (2007). Augmentation and combination strategies to treat the residual symptoms of major depressive disorder. Psychiatry (Edgmont), 4(2), 16. https://pmc.ncbi.nlm.nih.gov/articles/PMC2922343/
3. U.S. Food and Drug Administration (FDA). (2009). Label for Wellbutrin (Bupropion). https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/018644s039s040.pdf
4. Ashton, A. K., & Rosen, R. C. (1998). Bupropion as an antidote for serotonin reuptake inhibitor-induced sexual dysfunction. The Journal of Clinical Psychiatry, 59(3), 112–115. https://doi.org/10.4088/jcp.v59n0304
5. Thase, M., et al. (2005). Remission rates following antidepressant therapy with bupropion or selective serotonin reuptake inhibitors. The Journal of Clinical Psychiatry, 66(8), 974–981. https://doi.org/10.4088/JCP.v66n0803
6. Patel, K., Allen, S., Haque, M. N., Angelescu, I., Baumeister, D., & Tracy, D. K. (2016). Bupropion: A systematic review and meta-analysis of effectiveness as an antidepressant. Therapeutic Advances in Psychopharmacology, 6(2), 99. https://doi.org/10.1177/2045125316629071
7. Stahl, S. M., et al. (2004). A review of the neuropharmacology of bupropion. Primary Care Companion to The Journal of Clinical Psychiatry, 6(4), 159–166. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC514842/
8. DrugBank Online. (2024). Bupropion. https://go.drugbank.com/drugs/DB01156
9. Gitlin, M. J., Suri, R., Altshuler, L., Zuckerbrow-Miller, J., & Fairbanks, L. (2002). Bupropion-sustained release as a treatment for SSRI-induced sexual side effects. Journal of Sex & Marital Therapy, 28(2), 131–138. https://doi.org/10.1080/00926230252851870
10. Nieuwstraten, C. E., & Dolovich, L. R. (2001). Bupropion versus selective serotonin-reuptake inhibitors for treatment of depression. The Annals of Pharmacotherapy, 35(12), 1608–1613. https://doi.org/10.1345/aph.1A099
11. Papakostas, G. I., Trivedi, M. H., Alpert, J. E., Seifert, C. A., Krishen, A., Goodale, E. P., & Tucker, V. L. (2008). Efficacy of bupropion and the selective serotonin reuptake inhibitors in the treatment of anxiety symptoms in major depressive disorder: a meta-analysis of individual patient data from 10 double-blind, randomized clinical trials. Journal of Psychiatric Research, 42(2), 134–140. https://doi.org/10.1016/j.jpsychires.2007.05.012
12. Thase, M. E., Papakostas, G. I., Montgomery, S. A., Krishen, A., Katz, J. R., & Tucker, V. L. (2007). Comparing the rapidity of response during treatment of major depressive disorder with bupropion and the SSRIs: A pooled survival analysis of 7 double-blind, randomized clinical trials. The Journal of Clinical Psychiatry, 68(12), 3455. https://pubmed.ncbi.nlm.nih.gov/18162022/
13. Settle, E. C. (1998). Antidepressant drugs: disturbing and potentially dangerous adverse effects. Journal of Clinical Psychiatry, 59(Suppl 16), 25–30. https://pubmed.ncbi.nlm.nih.gov/9796863/
14. Zisook, S., Rush, A. J., Haight, B. R., Clines, D. C., & Rockett, C. B. (2006). Use of bupropion in combination with serotonin reuptake inhibitors. Biological Psychiatry, 59(3), 203–210. https://doi.org/10.1016/j.biopsych.2005.06.027