Enhancing Antidepressant Treatment with Bupropion: A Comprehensive Guide

In today's article, we delve into the use of bupropion as an adjunct to antidepressant medications, specifically adding bupropion to SSRI (Selective Serotonin Reuptake Inhibitors) antidepressants.

Understanding Bupropion

Bupropion is a norepinephrine and dopamine reuptake inhibitor (NDRI). This means it increases the levels of norepinephrine and dopamine in the prefrontal cortex of the brain, which helps boost mood, improve concentration, and enhance motivation. It’s commonly used in conjunction with SSRIs (Selective Serotonin Reuptake Inhibitors) to address residual symptoms of depression such as sad mood, decreased concentration, and lack of motivation.

Why Combine Bupropion with SSRIs?

Many patients on SSRIs still experience residual symptoms of depression. Bupropion can be added to their treatment plan to address these symptoms and potentially counteract side effects such as sexual dysfunction and weight gain associated with SSRIs. By combining bupropion with SSRIs, we can increase the levels of three key neurotransmitters: serotonin, norepinephrine, and dopamine. This combination can be particularly effective for patients who feel "stuck" in their current treatment due to the lingering of residual symptoms. We discuss the versatility of bupropion in this video.

Common Combinations and Their Benefits

Bupropion and Sertraline (Zoloft)

One of the most common combinations is bupropion with sertraline, often referred to as "Well-oft." Sertraline not only increases serotonin but also weakly inhibits the dopamine transport system, which complements the dopamine increase provided by bupropion. This combination has fewer drug interactions compared to other SSRIs, making it a safer choice for many patients.

Bupropion and Fluoxetine (Prozac)

Combining bupropion with fluoxetine leverages the 5-HT2C antagonism of fluoxetine, which increases norepinephrine and dopamine downstream. However, this combination requires caution due to bupropion’s strong inhibition of the CYP2D6 enzyme, which metabolizes fluoxetine. Patients need careful monitoring to avoid toxicity and serotonin syndrome.

Bupropion with Other SSRIs

Bupropion can also be combined with other SSRIs like Lexapro (escitalopram) and Celexa (citalopram). However, these combinations don’t offer the additional benefits seen with fluoxetine and sertraline. They primarily provide the serotonin increase from the SSRIs and the norepinephrine and dopamine boost from bupropion.

Cautions and Considerations

While combining bupropion with SSRIs can be beneficial, there are several important cautions to keep in mind:

1.Black Box Warning

Antidepressants carry a black box warning for increased suicidal ideation, and this risk can be higher when combining two antidepressants. Patients need close monitoring for any increase in suicidal thoughts. If suicidal thoughts arise seek immediate help as this is an emergency. In the United States, you can call the suicide crisis number 9-8-8 for support, call 9-1-1, and/or go to your nearest emergency room.

2. Seizure Risk

Both bupropion and SSRIs carry a seizure risk, and this risk is compounded when the medications are combined. Therefore, this combination is not recommended for patients with a history of seizures. If a patient has a seizure on antidepressants they must notify their provider right away and consider evaluation from a neurologist.

3. Serotonin Syndrome

Bupropion inhibits the metabolism of many SSRIs through the CYP2D6 pathway, increasing the risk of serotonin syndrome. Symptoms include agitation, confusion, rapid heart rate, and high blood pressure. Patients should be aware of these symptoms and seek medical attention if they occur.

4. Increased Anxiety

Bupropion can increase norepinephrine and dopamine, which may exacerbate anxiety symptoms in some patients. Those with anxiety disorders should approach this combination cautiously.

Alternative Approaches

Before resorting to combining multiple medications, it’s crucial to explore potential underlying causes of depression. Nutritional deficiencies (e.g., iron, vitamin D, magnesium), thyroid issues, and other health conditions can contribute to depressive symptoms. Addressing these root causes can sometimes alleviate the need for multiple medications.

Final Thoughts

Combining bupropion with SSRIs can be an effective strategy for managing depression, especially in treatment-resistant cases. However, it’s essential to approach this combination with caution, monitoring for side effects and potential drug interactions. Always consult with a healthcare provider to tailor the treatment to your specific needs.

Helpful Resources for Your Next Steps

With this knowledge, you can have informed discussions when seeking medical advice from your healthcare providers, pharmacist (pharm.d), and mental health professionals. 

Adding Bupropion can be an effective treatment for your mental health conditions, helping with your well-being. Understanding the specific uses, side effects, and drug interactions allows you to evaluate whether or not adding this medication to your treatment plan is right for you. However, it is important to remember that individual risk factors must also be considered, such as genetic errors of metabolism, nutrient status, underlying conditions, and much more.

At Levelheaded Mind, Jezel Rosa, PMHNP-BC, is available on a coaching/consultation basis to discuss your medication choices and help you explore whether adding Bupropion is your best treatment option. You can speak directly by scheduling a coaching/consultation session with Jezel Rosa, PMHNP-BC.

For more information about Bupropion and adding it to antidepressants, watch our video on the topic on YouTube.

Disclaimer: All the information on this website is for educational purposes and not intended to be specific/personal medical advice or substitute for diagnosis and treatment of any conditions discussed herein. Furthermore, reading our blogs, watching our videos, or getting answers to comments/questions does not establish a provider-patient relationship. Please consult with your own healthcare provider for proper diagnosis and treatment.

References

Dhillon, S., Yang, L. P., & Curran, M. P. (2008). Bupropion: a review of its use in the management of major depressive disorder. Drugs68(5), 653–689. https://doi.org/10.2165/00003495-200868050-00011

Jing, E., & Straw-Wilson, K. (2016). Sexual dysfunction in selective serotonin reuptake inhibitors (SSRIs) and potential solutions: A narrative literature review. The mental health clinician6(4), 191–196. https://doi.org/10.9740/mhc.2016.07.191

Kassandra J. Gibbs, B. A., & J. Alexander Bodkin, M. D. (2016). Adjunctive Treatment Options for Patients With Residual Symptoms of Depression. Www.psychiatrictimes.com33. https://www.psychiatrictimes.com/view/adjunctive-treatment-options-patients-residual-symptoms-depression

Stahl,S. (2021). Stahl’s Essential Psychopharmacology: Prescriber’s Guide, 7th Ed.

Stahl, S. (2021). Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, 5th Ed.

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