How Does Wellbutrin Help With Depression?

Summary: Wellbutrin can help with depression by affecting the amount of chemicals in the brain associated with mood, learning, memory, and thinking.

Key Points:

• Wellbutrin is an atypical antidepressant that’s FDA (Food and Drug Administration) approved for the treatment of major depressive disorder (MDD) and seasonal affective disorder (SAD), which are two types of depression.
• Wellbutrin is also FDA approved for smoking cessation, i.e. helping people quit smoking tobacco, and used off label to treat attention-deficit hyperactivity disorder (ADHD).
• The active ingredient in Wellbutrin is bupropion, which acts on norepinephrine transport molecules and dopamine transport molecules to achieve antidepressant effects.

First Generation, Second Generation, and Atypical Antidepressants

The first generation of antidepressants were called monoamine oxidase inhibitors (MAOIs). They were first discovered in the 1930s and reached patients by the 1950s, with tricyclic antidepressants (TCAs), also considered first generation, reaching patients by the 1960s.

The second generation of antidepressants appeared in the 1970s. These included selective serotonin reuptake inhibitors (SSRIs), which act on serotonin receptors, serotonin-norepinephrine reuptake inhibitors (SNRIs), which act on both serotonin and norepinephrine, and atypical antidepressants, which exert an effect on the same systems, but though different mechanisms.

Bupropion is an atypical antidepressant invented in 1969 and approved by the FDA in 1985. It’s a norepinephrine-dopamine reuptake inhibitor (NDRI) sold in various formulations under the commercia name we use in the title, Wellbutrin.

Let’s take a look at how Wellbutrin can help people with depression.

The Impact of Wellbutrin (bupropion) on Symptoms of Depression

We present the information below as a series of steps, but after step 1, the action of the medication is not necessarily sequential. After entering the brain, it acts in no particular order. We call them steps here out of convention. In fact, the medication can perform all the functions at once, or separately at different times, depending on exactly which molecules are present in the synaptic cleft, in which amounts, and when.

Here’s how Wellbutrin works.

Wellbutrin/Bupropion Mechanism(s) of Action: What it Does in Your Brain

Step 1:

Bupropion enters bloodstream, enters central nervous system, crosses blood brain barrier, enters brain.

Step 2:

Bupropion blocks a molecule called the norepinephrine transporter (NET). This increases the amount of norepinephrine in the space between neurons called the synaptic cleft. Moderate levels of norepinephrine are associated with alertness and clarity of thinking, while low levels are associated with low mood and high levels are associated with stress and/or panic.

Step 3:

Bupropion inhibits the action of a molecule called the dopamine transporter (DAT), which prevents the reabsorption – known as reuptake in this context – of dopamine into brain cells. Increased dopamine in the synaptic cleft is associated with enhanced motivation and improved mood.

Step 4:

While present in the synaptic cleft and actively affecting norepinephrine and dopamine, bupropion doesn’t affect serotonin. This decreases likelihood of experiencing common antidepressant side effects such as weight gain and decreased libido.

Step 5:

Bupropion also blocks – antagonizes in the language of neurobiology – nicotinic acetylcholine receptors, which reduces cravings for tobacco and nicotine withdrawal symptoms. This is why some medications containing bupropion are prescribed to help people stop smoking, i.e. smoking cessation.

Step 6:

By increasing the amount of norepinephrine and dopamine in the synaptic cleft, bupropion is thought to increase levels of a molecule called brain derived neurotropic factor (BDNF), which plays a key role in learning, memory, and neural plasticity, i.e. the ability of the brain to adapt and change to maintain optimal function.

That’s an overview of the neurobiology of Wellbutrin, or the physical mechanism by which Wellbutrin can help depression.

What are the Benefits of Wellbutrin for Depression?

Wellbutrin is available in several different formations, i.e. in different dosage and timed release variations. For details, please refer to this National Alliance on Mental Illness (NAMI) Bupropion Fact Sheet, which we also link to in the introduction, above.

The benefits of Wellbutrin for depression include:

• Reduced symptoms of major depressive disorder (MDD)
• Reduced symptoms of seasonal affective disorder (SAD)
• Decreased risk of sexual side effects, compared to other antidepressant medications.
• Minimal risk of weight gain as a side effect, compared to other antidepressant medications.

Those are the primary benefits of Wellbutrin, and why patients may choose it over a different medication. In most cases, the medication takes 4-6 weeks to reduce symptoms, and it’s necessary to keep taking the medication to maintain its antidepressant effect.

Now let’s take a look at the potential side effects of Wellbutrin, about which anyone with depression considering Wellbutrin should be aware. Potential side effects include:

• Headache
• Weight loss
• Dry mouth
• Insomnia
• Excess sweating
• Dizziness
• Constipation
• Elevated heart rate
• Sore throat

In rare cases, bupropion/Wellbutrin may cause more problematic side effects. These include ringing in ears, skin rash, nausea/stomach pain, muscular pain, anxiety, agitation, and, at higher doses, seizures. Black box FDA-required warnings for bupropion include the increased risk of suicidal thoughts or actions in children and adults underage 25. Here’s how NAMI describes this risk:

“Patients with MDD, both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications.”

However, if you have clinical depression, please understand that every antidepressant on the market has the same black box suicide warning. Therefore, the warning should raise your awareness, but evidence shows millions of people safely take medications with bupropion, i.e. Wellbutrin, every year.

Always Talk to Your Provider About Psychiatric Medication, Ask Every Question You Have

When considering any psychiatric medication for a disorder that has risk of suicide – such as major depressive disorder – it’s essential to have an open and honest conversation with thee prescribing physicians about the relative risks and benefits of that medication.

Here’s a helpful presentation on antidepressant risk published by Psychiatry Academy at Massachusetts General Hospital.

We’ll close with this set of data:

Bupropion prescriptions, 2014-2023:

• 2014: 25.1 million
• 2015: 26.2 million
• 2016: 23.8 million
• 2017: 254.9 million
• 2018: 24.5 million
• 2019: 25.7 million
• 2020: 28.8 million
• 2021: 29.1 million
• 2022: 25.2 million
• 2023: 30.4 million

Those figures should reassure anyone considering taking Wellbutrin to help with depression. Not only is it considered an effective medication, it’s in widespread use around the country. For millions of people every year, the rewards outweigh the risks.