Wellbutrin (bupropion) is an antidepressant commonly used to treat major depressive disorder and seasonal affective disorder, and it is also prescribed as an aid for smoking cessation. Unlike other antidepressants, it works by increasing the levels of norepinephrine and dopamine in the brain, neurotransmitters involved in motivation, energy, attention, and reward.
Wellbutrin may be especially helpful for patients experiencing fatigue, poor concentration, or low motivation as part of depression.
It is less likely to cause sexual dysfunction, weight gain, or emotional blunting than other antidepressants, which makes it a useful option for patients who cannot tolerate SSRIs or SNRIs. However, it can increase anxiety or insomnia in some individuals and increase the risk of seizures [1].
Wellbutrin is classified as an atypical antidepressant because it does not primarily affect serotonin, the defining feature of SSRIs. SSRIs work by selectively increasing serotonin levels, whereas Wellbutrin acts as a norepinephrine–dopamine reuptake inhibitor (NDRI).
Understanding Antidepressant Drug Classes
Antidepressants are commonly grouped into classes based on how they work in the brain. They include [2]:
- Selective Serotonin Reuptake Inhibitors (SSRIs): These increase serotonin levels in the brain and are one of the most commonly prescribed, first-line antidepressant treatments. Common SSRIs include Fluoxetine (Prozac), Sertaline (Zoloft), Citalopram (Celexa), and Escitalopram (Lexapro).
- Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): These affect both serotonin and norepinephrine levels. Common examples include Effexor and Cymbalta.
- Tricyclic Antidepressants: These are an older class of antidepressants typically used when SSRIs or SNRIs have not been effective, as they have more side effects. Common tricyclics include Amitriptyline, Nortriptyline, and Clomipramine.
- Atypical Antidepressants: These do not fit into other classes, as they each have unique mechanisms of action. Common atypical antidepressants include Wellbutrin and Trazodone.
How Does Wellbutrin Work?
Wellbutrin works by inhibiting the reuptake transporters for norepinephrine and dopamine. Dopamine activity is enhanced in brain regions involved in reward, motivation, and executive function, such as the mesolimbic and prefrontal pathways, which helps counter symptoms like low motivation and trouble focusing. Its effects on norepinephrine support alertness, energy, and stress response regulation through actions in cortical networks [3].
Wellbutrin also acts as a noncompetitive antagonist at nicotinic acetylcholine receptors. By reducing cholinergic stimulation of dopamine, it helps normalize reward signaling rather than simply increasing neurotransmitter levels.
Common Side Effects of Wellbutrin
There are some common side effects reported when first starting Wellbutrin. These are often mild and temporary, typically improving within a week or two. Regardless, you should always tell your provider about any side effects you are experiencing.
- Drowsiness or sudden increase in energy (restlessness)
- Lightheadedness
- Dry mouth
- Shakiness
- Nausea or vomiting
- Weight loss
- Trouble sleeping
- Muscle twitching
- Sore throat
Some rare but more serious side effects may occur. If you experience any of these, you should call your provider or seek medical attention immediately:
- Worsening symptoms of depression
- Suicidal thoughts
- Severe headaches or migraines
- Irregular or fast, pounding heartbeat
- Confusion or hallucinations
- Seizures or convulsions
Safety Risks and Considerations
Wellbutrin is generally safe and well-tolerated when prescribed appropriately, but certain individuals should avoid it or use it with caution. The largest risk is seizures, as bupropion lowers the seizure threshold.
Because of this, it is avoided in people with a seizure disorder or conditions that increase seizure risk, such as bulimia or anorexia nervosa, withdrawal from alcohol or benzodiazepines, and significant head trauma or brain tumors [4].
Patients with bipolar disorder should be carefully screened before starting bupropion, as it can contribute to mania or hypomania if used without a mood stabilizer. It may also raise blood pressure, especially when combined with nicotine replacement therapy, so blood pressure monitoring is recommended in patients with hypertension.
Can You Become Addicted to Wellbutrin?
Wellbutrin is not considered addictive, as it does not produce the euphoria, tolerance, or compulsive drug-seeking behavior that defines addiction. Although it increases dopamine signaling, it does so gradually and in a regulated way by blocking dopamine reuptake rather than causing rapid dopamine release.
Some people may experience discontinuation symptoms (such as irritability or low mood) if it is stopped cold turkey, but this is the brain readjusting, not addiction. Misuse has been reported in uncommon cases (such as crushing or snorting tablets in prisons, referred to as “jailhouse crack” or “poor man’s cocaine”) [5].
What Antidepressant Is Closest to Wellbutrin?
Atypical antidepressants like Wellbutrin (bupropion) are unique in their effect profile and work differently from other antidepressant classes, typically targeting the levels of more than one neurotransmitter in the brain. Other brands of bupropion include Aplenzin, Zyban, and Forfivo XL.
There is no medication that is the closest or most similar to bupropion, and if you are looking for alternatives, it’s best to talk with your doctor.
Medication Awareness and Education in Michigan
At Rushton Recovery, our supervised medical detox and residential treatment center offers a healing space to embark on your journey toward a drug-free life. Our compassionate team combines evidence-based therapies, medication management, and holistic healing activities in a serene environment to heal from substance abuse and mental health challenges.
We are also committed to providing education on commonly prescribed medications to support healthy habits and safe practices. However, never take or stop any medications without speaking first with your doctor.
Sources
[1] Medline Plus. Bupropion.
[2] Mayo Clinic. 2022. Antidepressants.
[3] Learned-Coughlin, S. (2004). A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor. Primary care companion to the Journal of clinical psychiatry, 6(4), 159–166.
[4] Huecker, M. et al. 2024. Bupropion. StatsPearl.
[5] Umudi, O. et al. (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, 15(3), e36189.