## **An overview of Wellbutrin**
When talking about alternatives to selective serotonin reuptake inhibitors (SSRIs), Wellbutrin, known generically as bupropion (Huecker et al., 2023), often arises in such discussions for good reason. As an atypical antidepressant, it works differently from serotonin-focused medications that patients may start with. Wellbutrin targets dopamine and norepinephrine, two neurotransmitters closely tied to mood regulation, energy levels, and focus. This is exactly what makes it stand out pharmacologically and clinically.
Primarily, Wellbutrin is prescribed for major depressive disorder (MDD) and to prevent seasonal affective disorder (SAD). Aside from that, under the name Zyban, bupropion can be used to treat bipolar disorder (Li et al., 2016) and is also FDA-approved as a smoking cessation aid (Centers for Disease Control and Prevention, 2022). Increasing dopamine levels and dampening the effects of nicotine on the brain's reward system, it helps curb cravings and withdrawal symptoms, making it a solid option for patients trying to quit smoking or stop smoking as part of nicotine replacement therapy.
Beyond the aforementioned benefits, Wellbutrin is also less likely to cause sexual dysfunction, weight gain, or sedation, which are common reasons patients discontinue other antidepressants. In fact, for patients struggling with fatigue, low motivation, or hypersomnia, Wellbutrin can often be a better fit.
There are three formulations available:
- Immediate-release (IR)
- Sustained-release (SR) (Wellbutrin SR or bupropion SR)
- Extended-release (XL) (Wellbutrin XL or bupropion extended release)
While Wellbutrin XL is approved for both MDD and SAD, the SR version is indicated to treat major depressive disorder only. The choice between formulations often depends on how well a patient tolerates the antidepressant medication and their preferences for dosing schedules.
That said, Wellbutrin isn't without risks. It's contraindicated in patients with a history of seizure disorder, eating disorder, head injury, or those withdrawing abruptly from alcohol or sedatives. And like all antidepressants, there's a boxed warning for increased suicidal thoughts in young adults and adolescents, especially in the early stages of treatment.
It's best to keep in mind, however, that while Wellbutrin offers a distinct therapeutic profile, it also requires careful screening and monitoring, particularly when used to treat depression, bipolar disorder, attention deficit hyperactivity disorder, or other mental illnesses.
## **Wellbutrin abuse**
Over the past two decades, bupropion misuse has been steadily climbing. In Ontario, Canada, for instance, authorities reported a 10-fold increase in suspicious bupropion prescriptions between 2000 and 2013, reaching nearly 48,000 flagged pills in just one year (Steele et. al., 2015). The United States is seeing similar trends. Poison control data from 2015 to 2017 showed a 36% rise in bupropion-related toxic exposures, with nearly 1 in 10 tied directly to abuse or misuse.
What's driving these? It's because of how wellbutrin works. By increasing dopamine and norepinephrine levels, bupropion hydrochloride produces stimulant-like effects—something some users describe as similar to cocaine or amphetamines (Stahl et.al, 2004). When taken in high doses, particularly outside of prescribed guidelines, the drug can trigger euphoria, heightened energy, and confidence, making it attractive to those seeking a “cheap high.” Hence, the street nickname: “poor person's cocaine.”
Routes of misuse include crushing and snorting or even injecting the medication, both of which are extremely dangerous and bypass the drug's extended-release tablet design. Beyond the immediate risk of overdose or adverse effects, these methods also introduce significant health complications, including infections and cardiovascular strain.
According to reports, dolescents and young adults are particularly at risk (Stassinos et al., 2016). Nearly 67% of abuse cases involve individuals under 40, with males most commonly represented (Baribeau & Araki, 2013). In fact, Wellbutrin has even become a form of underground currency in prison systems (Simpson, 2016). It goes by names like “Wellies,” “Dubs,” or “Barnies,” and 22.7% of documented cases have some tie to correctional settings (Aikoye et. al., 2023).
For clinicians like yourself, this means it's critical to stay vigilant—not just with patient education but also with prescription monitoring, especially in high-risk populations. Bupropion might not be a scheduled substance, but its misuse potential is real—and rising.
## **Common side effects**
Like most medications that act on the brain, wellbutrin side effects don't come without a few bumps, but many are mild, manageable, and tend to fade as the body adapts. Still, it's helpful to know what patients might report during those first few days or weeks of taking bupropion.
Some of the following symptoms are commonly reported:
- Dry mouth
- Insomnia or general trouble sleeping
- Nausea and vomiting
- Dizziness or lightheadedness
- Headache
- Constipation
- Increased sweating or night sweats
- Loss of appetite, sometimes leading to weight loss
- Sore throat
- Restlessness or mild agitation
- Tremors
- Tinnitus (ringing in the ears)
- Changes in taste
- Palpitations or a racing heartbeat
- Anxiety or nervousness
- Flushing
- Stomach discomfort or other digestive issues
Most of these symptoms are self-limiting. They often appear early in treatment and subside as the body adjusts to the medication. That said, if a patient experiences persistent or new or worsening depression, it's a good idea to reassess the dosage, dose reduction, or formulation and consider additional support for side effect management.
Clinicians should also be aware of less common but more serious reactions. These include seizures, hallucinations, manic or hypomanic episodes, elevated blood pressure, and suicidal thoughts. Wellbutrin carries a boxed warning from the FDA regarding the risk of suicidal thoughts and behaviors, particularly in young adults during the initial phase of treatment or after a dose adjustment.
>Like most medications that act on the brain, wellbutrin side effects don't come without a few bumps, but many are mild, manageable, and tend to fade as the body adapts.
In short, while Wellbutrin is generally well-tolerated, especially compared to other antidepressants, side effect monitoring remains essential, not just in the first few weeks, but throughout treatment as doses are adjusted or combined with other drugs or other medicines.
Like most medications that act on the brain, wellbutrin side effects don't come without a few bumps, but many are mild, manageable, and tend to fade as the body adapts.
## **Mild side effects**
Many patients starting Wellbutrin will notice a few mild Wellbutrin side effects early on, but the good news is that most of these tend to be short-lived. As the body adapts to the medication, typically over a few days to a couple of weeks, these symptoms often fade without the need for intervention.
Commonly reported mild side effects include:
- Dry mouth
- Insomnia or difficulty falling asleep
- Dizziness
- Sore throat
- Constipation
- Nausea
- Changes in appetite (either weight loss or weight gain)
- Tinnitus (ringing in the ears)
While these effects of bupropion are rarely dangerous, they can be bothersome enough to affect adherence, especially if patients aren't expecting them.
## **Serious side effects**
While Wellbutrin is generally well-tolerated and often favored over selective serotonin reuptake inhibitors, it's not without serious risks. The most concerning is the increased risk of seizures, particularly at higher doses or in patients with a seizure disorder, eating disorder, head injury, or kidney or liver disease.
Another issue is the potential for a serious allergic reaction, including rare but life-threatening responses to bupropion tablets or bupropion hydrobromide, such as hives, swelling, or fever. Suicidal thoughts, worsening depression, and panic attacks may occur, particularly in young adults, and Wellbutrin carries a boxed warning for these effects.
Behavioral changes like mania, delusions, or mental illness flare-ups also warrant attention (Dwyer and Hieber, 2016). Additional risks include high blood pressure, blurred vision, eye pain, and serious skin reactions like Stevens-Johnson syndrome.
When your patients receiving bupropion manifest these side effects, you must provide immediate evaluation. And prior to the patient's intake, you must carefully manage their initial dose and titration to quickly address any side effects before they worsen.
## **Safety measures and precautions to take**
Prescribing Wellbutrin means thinking beyond just symptom relief. While it's a powerful tool for treating depression and aiding smoking cessation, it comes with specific safety considerations that shouldn't be overlooked, especially during initiation and dose changes.
### **Suicidality monitoring**
Both Wellbutrin SR and XL carry an FDA boxed warning for increased risk of suicidal thoughts and behaviors, particularly in adolescents and young adults (MedlinePlus, 2018). While this warning applies to all antidepressants, you must still closely monitor your patient's mood and behavior changes (such as having sudden or strong feelings), especially during the first few weeks of therapy or after any dosage adjustment.
### **Seizure risk**
Bupropion is one of the few antidepressants that lowers the seizure threshold, and the risk increases at higher doses. You should not prescribe the medication for patients with a history of seizures, eating disorders (like bulimia or anorexia), or abrupt withdrawal from alcohol or benzodiazepines.
### **Alcohol and substance use**
Alcohol can heighten the risk of neuropsychiatric side effects, including seizures and mood disturbances. It's best to have a conversation around lifestyle risks and be extra cautious with patients who have a history of alcohol or substance abuse.
### **Blood pressure monitoring**
Though not a first-line concern for most prescribers, Wellbutrin can elevate blood pressure in some individuals. It is advise that you monitor your patient, particularly in those with pre-existing hypertension or cardiovascular conditions.
### **Drug interactions to watch for**
Wellbutrin (bupropion) can interact with several medications, and it's important to review a patient's full medication list before prescribing. It is contraindicated with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis; a sufficient washout period is required when switching between these medications.
Caution is also needed when combining bupropion with antipsychotics or other antidepressants, as certain combinations may increase the risk of serotonin syndrome or lower the seizure threshold.
Additionally, because bupropion is a substrate of CYP2B6 enzyme and a dose-dependent inhibitor of CYP2D6, it can raise levels of CYP2D6 substrates (e.g., many antidepressants and antipsychotics). CYP2B6 inhibitors such as clopidogrel can increase bupropion exposure and decrease hydroxybupropion; monitor and adjust as needed. Regular monitoring and dose adjustments may be necessary when these interactions are present.
### **Other precautions**
Wellbutrin is a norepinephrine-dopamine reuptake inhibitor (NDRI), not a selective serotonin reuptake inhibitor. You should remind your patients of this distinction, as it explains why its side effect profile differs from that of commonly prescribed SSRIs, such as Lexapro or Zoloft.
If your patient has a missed dose, they should be advised to skip it rather than double up, as taking extra doses increases the risk of seizures. Bupropion has a half-life of approximately 21 hours, with full clearance typically occurring within four days—information that can be useful when planning a taper or switching to another medication.
### **When to seek immediate help**
Advise patients to seek immediate emergency medical attention if they experience any of the following symptoms while taking Wellbutrin: seizures, suicidal thoughts or behaviors, severe allergic reactions (such as swelling, rash, or difficulty breathing), uncontrolled hypertension, or psychiatric symptoms like hallucinations or manic episodes. Prompt intervention is essential to ensure patient safety and prevent serious complications.
>Prescribing Wellbutrin means thinking beyond just symptom relief. While it’s a powerful tool for treating depression and aiding smoking cessation, it comes with specific safety considerations that shouldn’t be overlooked, especially during initiation and dose changes.
## **References**
Aikoye, S., Basiru, T. O., Nwoye, I., Adereti, I., Asuquo, S., Ezeokoli, A., Hardy, J., & Umudi, O. (2023). A systematic review of abuse or overprescription of bupropion in American prisons and a synthesis of case reports on bupropion abuse in American prison and non-prison systems. Cureus. https://doi.org/10.7759/cureus.36189
Baribeau, D., & Araki, K. F. (2013). Intravenous bupropion: A previously undocumented method of abuse of a commonly prescribed antidepressant agent. Journal of Addiction Medicine, 7(3), 216–217. https://doi.org/10.1097/adm.0b013e3182824863
Centers for Disease Control and Prevention. (2022, February 3). How to use bupropion SR | Quit smoking | Tips from former smokers | CDC. https://www.cdc.gov/tobacco/campaign/tips/quit-smoking/quit-smoking-medications/how-to-use-quit-smoking-medicines/how-to-use-bupropion-sr.html
Dwyer, S., & Hieber, R. (2016). Mania possibly linked with bupropion for smoking cessation: A case report. Mental Health Clinician, 6(6), 314–317. https://doi.org/10.9740/mhc.2016.11.314
Huecker, M. R., Smiley, A., & Saadabadi, A. (2023). Bupropion. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK470212/
Li, D.-J., Tseng, P.-T., Chen, Y.-W., Wu, C.-K., & Lin, P.-Y. (2016). Significant Treatment Effect of Bupropion in Patients With Bipolar Disorder but Similar Phase-Shifting Rate as Other Antidepressants. Medicine, 95(13), e3165. https://doi.org/10.1097/md.0000000000003165
MedlinePlus. (2018). Bupropion: MedlinePlus drug information. https://medlineplus.gov/druginfo/meds/a695033.html
Simpson, J. (2016). Psychopharmacology in jails: An introductionhttp://www.antoniocasella.eu/archipsy/psychopharmacology_may16.pdf
Stahl, S. M., Pradko, J. F., Haight, B. R., Modell, J. G., Rockett, C. B., & Learned-Coughlin, S. (2004). A review of the neuropharmacology of bupropion, a dual norepinephrine and dopamine reuptake inhibitor. The Primary Care Companion to the Journal of Clinical Psychiatry, 6(4), 159–166. https://doi.org/10.4088/pcc.v06n0403
Stassinos, G. L., & Klein-Schwartz, W. (2016). Bupropion “abuse” reported to US poison centers. Journal of Addiction Medicine, 10(5), 357–362. https://doi.org/10.1097/adm.0000000000000249
Steele, L. S., Macdonald, E. M., Gomes, T., Hollands, S., Paterson, J. M., Mamdani, M. M., Juurlink, D. N., & Canadian Drug Safety and Effectiveness Research Network. (2015). Rates of anomalous bupropion prescriptions in Ontario, Canada. Annals of Family Medicine, 13(4), 343–346. https://doi.org/10.1370/afm.1818
