How Does Wellbutrin Work? All About Its Mechanism of Action

Wellbutrin (bupropion) is an antidepressant. But it works differently than most medications used to treat depression. Other antidepressants, like selective serotonin reuptake inhibitors (SSRIs), increase a chemical called serotonin. But Wellbutrin doesn’t have this effect.

Even though it works differently than other antidepressants, Wellbutrin is still considered a first-choice medication for depression. Here, we’ll dive into how Wellbutrin works, how to tell if it’s working, and how it compares to other antidepressants.

What’s Wellbutrin?  

Wellbutrin is part of a group of medications called atypical antidepressants. It comes in three forms:

• Immediate-release (IR) tablets

• Sustained-release (SR) tablets (Wellbutrin SR)

• Extended-release (XL) tablets (Wellbutrin XL, Forfivo XL, Aplenzin)

All three forms are approved to treat depression. Wellbutrin XL is also approved to treat seasonal affective disorder (SAD). And generic bupropion SR tablets are approved to help people quit smoking.

Good to know: Wellbutrin IR tablets are no longer available as a brand-name product. But the name Wellbutrin is well-known. So we’ll refer to all bupropion products as Wellbutrin throughout this article.

How does Wellbutrin work?

Wellbutrin works in a few ways. The effects that you’ll notice will depend on why you’re taking it.

Depression and SAD

Wellbutrin’s primary action is boosting levels of two brain chemicals called dopamine and norepinephrine. This is different from many other antidepressants, which work by increasing serotonin levels in the brain. Wellbutrin has minimal impact on serotonin levels.

Dopamine and norepinephrine are naturally occurring chemicals that have an impact on mood, among many other functions. When there’s more of these chemicals available for the brain to use, a person’s mood may improve. This is beneficial for people with depression or SAD.

But how exactly does Wellbutrin increase dopamine and norepinephrine levels? Typically, dopamine and norepinephrine carry messages between nerve cells, which then absorb the chemicals. Wellbutrin blocks this process, known as reuptake, freeing up more dopamine and norepinephrine for the brain to use.

As mentioned, higher levels of these chemicals is associated with improved mood. So it makes sense that many people report feeling happier and more balanced while taking Wellbutrin.

Quitting smoking

 Wellbutrin may help people quit smoking in two major ways:

1. By reducing some symptoms of nicotine withdrawal: Smoking cigarettes causes a surge in dopamine and norepinephrine levels in the body. When you quit smoking, you feel withdrawal symptoms (like irritability and trouble concentrating) due to a decrease in these chemicals. By increasing dopamine and norepinephrine levels, Wellbutrin makes nicotine withdrawal less intense.

2. By reducing nicotine cravings: It does this by blocking nicotine receptors (binding sites) in the body. When nicotine receptors are blocked, nicotine becomes less pleasurable. This makes you less likely to want to smoke.

Other conditions

Wellbutrin is sometimes prescribed for reasons other than its FDA-approved uses. These are called off-label uses. For example, Wellbutrin is sometimes prescribed for attention-deficit hyperactivity disorder (ADHD).

In people with ADHD, there may be an imbalance of brain chemicals like dopamine and norepinephrine. This is why stimulant medications that increase these chemicals — like Adderall (amphetamine salts) — are prescribed for people with ADHD. As mentioned, Wellbutrin also increases levels of dopamine and norepinephrine.

Wellbutrin may also help some people lose weight. In fact, it’s one of the active ingredients in a medication called Contrave (naltrexone / bupropion), which is FDA approved for weight loss. 

Boosting levels of dopamine and norepinephrine may reduce your desire to eat. This is because dopamine and norepinephrine levels increase after eating. By boosting these chemicals in the absence of food, Wellbutrin may be able to suppress hunger.

Does Wellbutrin start working immediately?

No, Wellbutrin doesn’t start working immediately. If you’re taking Wellbutrin for depression, you may begin feeling its positive effects within a few weeks. But it can take a couple of months to feel the full effects. 

Most oral antidepressants have a similar timeline. However, one oral antidepressant that contains bupropion — Auvelity (bupropion / dextromethorphan) — may be effective within just 1 week of treatment.

How do you know if Wellbutrin is working?

If you’re taking Wellbutrin for depression, you can tell it’s working if your symptoms improve. This might mean that you:

• Have more energy

• Are sleeping better

• Have a regular appetite again

• Feel less anxious and depressed

• Are enjoying life more easily

• Are able to complete your daily activities with more ease

Remember, you won’t feel all of your depression symptoms improve right away. So keep in close contact with your healthcare professional and let them know how you’re doing. If you don’t feel like Wellbutrin is working after a few weeks, they can help you decide if it’s time to try a different antidepressant.

Other treatment options, including therapy, may also help you manage depression. In fact, combining therapy and medications may be more effective than either treatment option alone.

How is Wellbutrin different from other antidepressants?

Wellbutrin has several differences from other commonly prescribed antidepressants like SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs). Some of these differences include:

• Wellbutrin is less likely to cause weight gain, sexual side effects, and sleepiness. These common SSRI and SNRI side effects are less likely with Wellbutrin. In fact, Wellbutrin is the antidepressant of choice for people who can’t tolerate the sexual side effects of other antidepressants. It can even be prescribed along with SSRIs to relieve SSRI-induced sexual dysfunction.

• Wellbutrin may be more likely to cause dry mouth, headache, and trouble sleeping. Wellbutrin may be more likely to cause certain side effects than other antidepressants. For example, Wellbutrin is more likely than Lexapro (escitalopram) and Zoloft (sertraline) to cause headache, dry mouth, and trouble sleeping.

• Wellbutrin shouldn’t be taken if you have a history of seizures. While rare, Wellbutrin increases the risk of seizures, especially in people who are higher risk. People at higher risk of seizures include those with a history of a seizure disorder or a current or prior eating disorder. On the other hand, SSRIs and SNRI aren’t known to increase the risk of seizures.

• Wellbutrin isn’t typically used to treat anxiety. SSRIs and SNRIs are first-choice treatment options for anxiety.

• Wellbutrin is used to help people quit smoking. Most other antidepressants aren’t known to help you stop smoking.

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Written by:

Alexa Mader, PharmD

Alexa Mader has been a practicing pharmacist since 2018. She earned her Doctor of Pharmacy degree from the University of Georgia College of Pharmacy.

Edited by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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