Wellbutrin® vs. Lexapro®: A Guide

Depression — which is marked by a persistent lack of interest and low mood — is a common mental health condition. In 2021 alone, 8.3 percent of American adults experienced a depressive episode.

While experiencing depression can undoubtedly be difficult, there’s good (and hopeful) news: Major Depressive Disorder (MDD) and other types of depression are treatable. 

Wellbutrin® (bupropion) and Lexapro® (escitalopram) are two common medications prescribed to manage MDD symptoms, helping improve mood and work toward recovery.

Wellbutrin and Lexapro are both effective antidepressant medications. But they also have many differences, which may make one a better choice for you than the other. 

Read on to learn more about Wellbutrin vs. Lexapro and how each medication works in detail.

The Food and Drug Administration approved Wellbutrin in 1985 for the treatment of depression.

Often referred to as an atypical antidepressant, Wellbutrin belongs to a class of antidepressants referred to as norepinephrine-dopamine reuptake inhibitors (NDRIs). So, if you’ve been wondering, is Wellbutrin an SSRI? The answer is no — it’s an NDRI. 

The active ingredient in Wellbutrin is bupropion. In the United States, bupropion is sold under a variety of brand names, including Wellbutrin SR®, Wellbutrin XL® and Aplenzin®. 

It’s also sold as a generic medication, typically just as “bupropion.”

Wellbutrin comes in tablet form in several doses. As a treatment for depression, it’s typically prescribed for use two to three times daily. 

Wellbutrin Uses

Although it’s best known for its effects on the symptoms of depression, bupropion is also FDA-approved for smoking cessation (quitting smoking) and as a treatment for seasonal affective disorder (SAD).

Off-label, it’s sometimes prescribed to treat the following:

• Attention-deficit/hyperactivity disorder (ADHD)

• Overweight and Obesity

• Bipolar Disorder

• Antidepressant-induced sexual dysfunction

Lexapro is FDA-approved to treat major depressive disorder and generalized anxiety disorder (GAD). It belongs to a class of medications referred to as selective serotonin reuptake inhibitors (SSRIs).

The active ingredient in Lexapro is escitalopram. Like bupropion, escitalopram is also available as a generic medication. 

Lexapro is available in tablet form and as an oral solution.

Lexapro Uses

This medication is typically prescribed for use once per day to treat depression and generalized anxiety disorder.

Off-label, it’s sometimes prescribed to treat:

• Obsessive-compulsive disorder (OCD)

• Panic disorder and panic attacks

• Post-traumatic stress disorder (PTSD)

• Premenstrual dysphoric disorder (PMDD)

Check out our in-depth guide for further information on Lexapro.

Wellbutrin and Lexapro have several major differences you should be aware of if you’re considering a prescription in conversation with your healthcare provider.

Before we break them all down, it’s worth highlighting what they have in common: They’re both antidepressants typically prescribed to treat major depressive disorder, and they’re both effective — with a large volume of research showing they work well for most people.

Now, let’s dig into the differences.

Type of Antidepressant: NDRI vs. SSRI

Although Wellbutrin and Lexapro are both antidepressants, they belong to different drug classes and function in different ways inside your body.

A simple way to think of these medications is as two separate vehicles, each traveling to the same place via a different route. Although both vehicles will get to their destination, they take slightly different paths on the way. 

How Wellbutrin Works

Bupropion, Wellbutrin's active ingredient, is an NDRI that works by increasing the amount of norepinephrine and dopamine available in the brain. These neurotransmitters are key in regulating mood, cognitive function, and behavior.

For example, norepinephrine helps to manage your sleep-wake cycle, your ability to focus on a specific task, and your ability to form memories. It also helps manage certain emotions. 

High levels of norepinephrine are associated with feelings of happiness, hyperactivity, and high blood pressure. Low levels of norepinephrine, on the other hand, are linked to depression and anxiety disorders.

Dopamine is involved in reward-seeking, motivation, and movement, and research suggests that a high level of the neurotransmitter is associated with greater focus on mentally demanding tasks.

Researchers believe that bupropion treats depression by acting on these neurotransmitters to improve mood and manage depression symptoms.

Typically, Wellbutrin starts to work within the second week of the medication’s use. That said, it can also take up to several weeks.

How Lexapro Works

Escitalopram, the active ingredient in Lexapro, is an SSRI that works by increasing the amount of serotonin — another neurotransmitter — in your brain. It has various functions within the brain and body, such as regulating mood and feelings of happiness and anxiety.

While Wellbutrin treats depression by increasing the levels of dopamine and norepinephrine in the brain, Lexapro specifically targets serotonin. 

Although findings are mixed, a large amount of research supports the theory that people with depression have reduced levels of serotonin.

Other research has shown that low levels of certain serotonin byproducts may contribute to an increased risk of suicide.

Lexapro doesn’t start working immediately. It can take a few weeks to start working as a treatment for depression and anxiety disorders, so you may not notice any improvements right away. 

Lexapro's half-life is between 27 hours and 32 hours, which means that if you take Lexapro, each dose will take approximately 27 hours to 32 hours to reach half its concentration. Since it’s longer than 24 hours, it only has to be taken once a day.

Although both medications typically come in oral tablet form, Wellbutrin and Lexapro are prescribed at different doses.

Wellbutrin Dosages

Wellbutrin is sold in tablet form. The extended release formulation is most commonly used and is available in strengths of 150 mg or 300 mg per tablet. For depression, it’s typically prescribed at an initial dose of 150 mg per day. 

The extended release formulation allows it to be taken once a day.

Over time, this dosage may be increased to 300 mg per day. For depression, Wellbutrin may be used at a maximum dosage of 450 mg per day.

Wellbutrin can be taken with or without food. Make sure not to adjust your dosage or stop using this medication without first talking to your healthcare provider.

You can read our complete guide to learn more about Wellbutrin dosage information.

Lexapro Dosages

Lexapro is sold in tablet form in strengths of 5 mg, 10 mg, or 20 mg per tablet. It’s also available as an oral solution. 

For depression, it’s typically prescribed at a starting dosage of 10 mg per day, administered once daily.

Your healthcare provider may adjust your Lexapro dosage to a maximum of 20 mg per day over time. 

Lexapro can be taken with or without food. As with other antidepressants, it’s important not to make any changes to your dosage or discontinue usage without first talking to your healthcare provider.

Modern antidepressants are safe, easy to use, and effective for the vast majority of people, and Wellbutrin and Lexapro are no exception. 

However, like all antidepressants, both medications may cause side effects. Although many of the side effects of Wellbutrin and Lexapro are similar, there are some differences you should be aware of before using either antidepressant.

Common side effects of Wellbutrin and generic bupropion include:

• Agitation

• Dry mouth

• Constipation

• Headache/migraine

• Nausea and vomiting

• Dizziness

• Excessive sweating

• Tremor

• Insomnia

• Blurred vision

• Tachycardia and cardiac arrhythmia (abnormal heart rate or rhythm)

• Confusion

• Rash

• Hostility

• Auditory disturbance

The FDA label also contains a warning for more serious side effects, like suicidal thoughts and ideation.

Bupropion shouldn’t be taken by those who have a history of seizures or have had or have an eating disorder.

If you’re breastfeeding or pregnant or plan to be soon, make sure to let your healthcare provider know before taking Wellbutrin.

Common side effects of Lexapro and generic escitalopram include:

• Insomnia

• Ejaculation disorder (primarily delayed ejaculation)

• Nausea

• Excessive sweating

• Fatigue

• Somnolence (sleepiness or drowsiness)

• Decreased libido (low sex drive)

• Anorgasmia (difficulty or inability to reach orgasm)

• Weight gain

Serotonin syndrome is another potential side effect of SSRIs and SNRIs, but it happens more often because of drug interactions with:

• Monoamine oxidase inhibitors (MAOIs)

• Antipsychotics

• Blood thinners

Serotonin syndrome can occur when there’s too much serotonin in your body and may cause confusion, seizures, and unconsciousness.

Other potentially serious side effects include an increased risk of suicidal thoughts in children and adolescents.

As with Wellbutrin, you should talk to your provider if you are or plan to be breastfeeding or pregnant before using Lexapro.

Sexual Side Effects

The first key difference is the risk of sexual adverse effects, such as decreased libido and orgasm/ejaculation issues with Lexapro. In fact, all SSRIs can cause sexual side effects, including reduced level of interest in sex and difficulty achieving orgasm.

Unlike most antidepressants, Wellbutrin doesn’t appear to cause these side effects. In fact, one small study of men and women prescribed SSRIs found that their sexual side effects got better after they started using bupropion, the active ingredient in Wellbutrin.

An earlier study on the same topic also indicated that bupropion helps alleviate many of the sexual side effects associated with SSRI use.

On the other hand, clinical trials of Lexapro have shown that up to seven percent of users experienced reduced interest in sex, while between nine and 14 percent reported ejaculation-related side effects.

Body Weight Side Effects

Another key difference between Wellbutrin and Lexapro is their effect on body weight. Studies on SSRIs have shown that Lexapro tends to lead to a slight increase in body weight during long-term use.

For instance, one comparative study of various antidepressants found that escitalopram produced a mild average weight gain of 0.75 lbs over six months.

In contrast, you may wonder, does Wellbutrin cause weight gain? Research suggests that it’s more likely to cause weight loss than weight gain. One study looking at the relationship between antidepressants and weight gain found that bupropion was the only medication that produced weight loss.

Another study showed that bupropion enhanced weight loss in adults with obesity over a period of 48 weeks.

In fact, because of bupropion’s effects on body weight, it’s one of two active ingredients in the weight loss medication Contrave®, or naltrexone/bupropion.

To sum it up, research shows that Lexapro usually causes a small amount of weight gain, whereas Wellbutrin is more commonly associated with weight loss.

Finally, when it comes to effectiveness, research largely shows that Wellbutrin and Lexapro are both reliable treatments for depression.

In one study, researchers compared the effectiveness of Wellbutrin and Lexapro in people with moderate to severe depression.

The study participants received either generic bupropion, generic escitalopram, or a placebo for eight weeks, with their depression symptoms tracked and monitored using the Hamilton Rating Scale for Depression (HAM-D-17) and Hospital Anxiety and Depression (HAD) scale.

The researchers concluded that the medications were similarly effective at treating depression, but that bupropion was less likely to cause sexual side effects.

Other research has found that Wellbutrin and Lexapro are especially effective when used as a form of combination therapy.

In short, both medications work well for depression. However, if you’re prone to sexual side effects, Wellbutrin may be the better choice for you. Unfortunately, Wellbutrin doesn’t work very well for anxiety. You’re better off with Lexapro, some other SSRI, or an SNRI if treating anxiety is your chief concern.

Sometimes, these two medications can work as a team. According to one study, taking Wellbutrin and Lexapro together was more effective as a treatment than taking one or the other solo. The study suggests that the combination of Wellbutrin and Lexapro is effective and even well-tolerated. 

Another study found that after four weeks of combining Wellbutrin and Lexapro, depression scores decreased significantly more in those who took the combination over a placebo.

In addition to Wellbutrin and Lexapro, numerous other medications are used to treat depression and anxiety disorders. These include:

• Selective serotonin reuptake inhibitors (SSRIs). Other SSRIs include fluoxetine (Prozac®), paroxetine (Paxil®), fluvoxamine (Luvox®), and sertraline (Zoloft®).

• Serotonin-norepinephrine reuptake inhibitors (SNRIs). Common SNRIs include duloxetine (Cymbalta®), desvenlafaxine (Pristiq®), and venlafaxine (Effexor XR®).

• Older classes of antidepressants. In certain cases, older antidepressants, such as tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), are also prescribed to treat depression. 

Wellbutrin and Lexapro are somewhat similar medications and popular treatment options for depression. 

Both are antidepressants supported by a large amount of scientific research, and both have a long track record of producing improvements — often significant.

However, when examining Wellbutrin vs. Lexapro, you’ll note some key differences. Here’s what to keep in mind:

• They have different mechanisms of action, meaning they work on different chemicals in the brain. Wellbutrin is an NDRI, while Lexapro is an SSRI.

• Wellbutrin and Lexapro share many of the same side effects, but there are two key differences: Lexapro produces a higher rate of sexual side effects, and Wellbutrin is linked to weight loss, while Lexapro can cause some weight gain.

• They come in different doses, though they’re both oral tablets.

• Both medications treat depression, but Wellbutrin is also considered a treatment for smoking cessation and is used off-label to treat ADHD, while Lexparo can also treat anxiety disorders.

You may want to keep these differences in mind when discussing these medications with your healthcare provider.

If you’re concerned you may have depression, it’s important to reach out to a mental health provider for help. A psychiatry provider can help you figure out if medication is the right course of action for you, and whether bupropion or one of several SSRIs is a better choice. 

If you’re ready to take the next step, Hers offers a range of mental health services, including options such as depression medication online.