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Drug vs. Drug

Wellbutrin vs. Lexapro: Differences, similarities, and which is better for you

Kristi Torres writer headshot By | Updated on May 19, 2020

Drug overview & main differences | Conditions treated | Efficacy | Insurance coverage and cost comparison | Side effects | Drug interactions | Warnings | FAQ

Wellbutrin and Lexapro are two prescription medications that are used in the treatment of major depressive disorder, or MDD. MDD is characterized by a low mood for at least a two week period through most situations. People with MDD may exhibit a loss of interest in activities they normally enjoy, low energy, and/or pain without any known cause. For some, counseling or physical activity may effectively control symptoms of depression, but for many, medication may be needed.

There are several types of medications that treat depression. Wellbutrin works by increasing available dopamine and norepinephrine, while Lexapro increases available serotonin. While both drugs work to treat depression, they do so by acting on different neurotransmitters which affect mood. Learn more about the differences below.

What are the main differences between Wellbutrin and Lexapro?

Wellbutrin (bupropion) is a prescription medication indicated in the treatment of major depressive disorder (MDD) and seasonal affective disorder. The active ingredient, bupropion, is also approved for use in smoking cessation in its sustained-release formulation. This was previously marketed under the brand name Zyban. Wellbutrin works as a dopamine and norepinephrine reuptake inhibitor at the neuronal level. This leaves higher levels of each of these neurotransmitters freely available, and dopamine and norepinephrine levels play an important role in mood and affect.

Wellbutrin is available in an immediate-release tablet in 75 mg and 100 mg. The sustained-release tablet indicated for every 12-hour dosing is available in 100 mg, 150 mg, and 200 mg. The extended-release tablet indicated for once every 24-hour dosing is available in 150 mg and 300 mg.

Lexapro (escitalopram) is also a prescription medication indicated in the treatment of major depressive disorder. Lexapro belongs to the group of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). Lexapro works by blocking the reuptake of serotonin at the neuronal membrane transport pump. This action effectively leaves more free serotonin in the neuron synapse. Other SSRIs you may be familiar with include Prozac, Zoloft, Celexa, or Paxil.

Lexapro is available as an oral tablet in strengths of 5 mg, 10 mg, and 20 mg. It is also available as an oral solution in a 5 mg/5 ml concentration.

Main differences between Wellbutrin and Lexapro
Wellbutrin Lexapro
Drug class Dopamine/ Norepinephrine reuptake inhibitor Selective serotonin reuptake inhibitor
Brand/generic status Brand and generic available Brand and generic available
What is the generic name? Bupropion Escitalopram
What form(s) does the drug come in? Immediate-release, sustained-release, and extended-release tablet Oral tablet and oral solution
What is the standard dosage? 150 mg once per day 10 mg once per day
How long is the typical treatment? Long-term (months to years) Long-term (months to years)
Who typically uses the medication? Adolescents and adults Adolescents and adults

Conditions treated by Wellbutrin and Lexapro

Wellbutrin and Lexapro are both indicated in the treatment of major depression. MDD is characterized by prolonged (2 weeks or more) feelings of low mood and decreased energy levels. It is possible that patients may not find joy in things they enjoyed previously.

Lexapro is also indicated in the treatment of generalized anxiety disorder (GAD). GAD is characterized by prolonged and obsessive worrying about a variety of topics.

Bupropion, the active ingredient in Wellbutrin, carries a unique indication for smoking cessation. Although the mechanism is not entirely understood, patients taking bupropion are more likely to be able to achieve smoking cessation. A systematic review of numerous studies with an overall large sample size supports this statement, though patients may experience more adverse events than with other smoking cessation interventions.

Wellbutrin and  Lexapro are both used off-label in a variety of psychological disorders that are closely related to depression. The following is not intended to be a complete listing of potential uses for Wellbutrin and Lexapro. Only your healthcare professional can diagnose your disorder and decide which treatment option is best for you.

Condition Wellbutrin Lexapro
Major depressive disorder Yes Yes
Seasonal affective disorder Yes No
Smoking cessation Yes No
Generalized anxiety disorder No Yes
Attention-deficit disorder Off-label No
Bipolar depression Off-label No
Augmentation of SSRI induced sexual dysfunction Off-label No
Binge eating disorder No Off-label
Bulimia nervosa No Off-label
Obsessive compulsive Disorder No Off-label
Panic disorder No Off-label
Post traumatic stress disorder No Off-label
Premenstrual dysphoric disorder No Off-label
Premature ejaculation No Off-label

Is Wellbutrin or Lexapro more effective?

Researchers have sought to compare Wellbutrin and Lexapro both as singular therapy for MDD, as well as dual therapy. One trial evaluated the efficacy of Wellbutrin as single therapy as compared to Lexapro single therapy. This study also sought to compare the prevalence of negative sexual side effects. The results found that Wellbutrin and Lexapro produced similar improvements in depressive symptoms, however, Wellbutrin was significantly less likely to cause sexual dysfunction.

Wellbutrin and Lexapro affect different neurotransmitters and are oftentimes used together. The results of one clinical trial found that the use of both drugs together leads to significantly higher response and symptom remission rates as compared to typical monotherapy with SSRIs. While further studies may be warranted, this study suggests some value in dual therapy with both medications.

Coverage and cost comparison of Wellbutrin vs. Lexapro

Wellbutrin is a prescription medication that is typically covered by both commercial and Medicare drug plans. The out-of-pocket price for generic Wellbutrin XL 150 mg can be more than $175, but with a coupon from SingleCare, you could get it for around $15.

Lexapro is also a prescription medication that is typically covered by both commercial and Medicare drug plans. Similar to Wellbutrin, the out-of-pocket price for a 30 day supply of generic Lexapro 10 mg can be as much as $180. SingleCare offers a coupon for generic Lexapro, which lowers the price to $15.

Wellbutrin Lexapro
Typically covered by insurance? Yes Yes
Typically covered by Medicare? Yes Yes
Standard dosage 30, 150 mg XL tablets 30, 10 mg tablets
Typical Medicare Part D copay Less than $10 Less than $10
SingleCare cost $13-$36 $15-$70

Common side effects of Wellbutrin vs. Lexapro

Wellbutrin and Lexapro affect the levels of different neurotransmitters. While their potential to cause certain side effects may be similar, there are some key differences.

Lexapro, like other SSRIs, has the potential to cause decreased libido or sex drive. Wellbutrin had no reported incidence of decreased libido. Research has shown that 42% of men and 15% of women will discontinue their antidepressant therapy due to sexual side effects. Compliance is an important factor in treating depression, so awareness of this side effect is important in managing a patient’s therapy.

Wellbutrin causes headache in as much as a quarter of the patients who take it, while headaches were not reported with Lexapro.  Wellbutrin and Lexapro both may cause nausea, vomiting, sweating, and diarrhea.

The following list is not intended to be a complete list of adverse events. Please consult a pharmacist, doctor, or another medical professional for a complete list of possible side effects.

Wellbutrin Lexapro
Side effect Applicable? Frequency Applicable? Frequency
Asthenia Yes 2% No n/a
Nausea Yes 13% Yes 5%
Dry mouth Yes 17% Yes 5%
Sweating Yes 6% Yes 5%
Vomiting Yes 4% No n/a
Diarrhea Yes 5% Yes 8%
Constipation Yes 10% Yes 3%
Dyspepsia No n/a Yes 3%
Dizziness Yes 7% No n/a
Somnolence Yes 2% Yes 6%
Agitation Yes 3% No n/a
Headache Yes 26% No n/a
Decreased appetite Yes 5% Yes 3%
Decreased libido No n/a Yes 2%
Weight loss Yes 14% No n/a
Weight gain Yes 3% No n/a

Source: Wellbutrin (DailyMed) Lexapro (DailyMed)

Drug interactions of Wellbutrin vs. Lexapro

Wellbutrin is a major substrate of CYP2B6 and a strong inhibitor of CYP2D6. If co-administration of Wellbutrin and a CYP2D6 substrate is needed, it may be necessary to decrease the dose of the 2D6 substrate. Some examples of CYP2D6 substrates include fluoxetine, sertraline, haloperidol, risperidone, and metoprolol.

Lexapro is a major substrate of CYP2C19 and CYP3A4, and a weak inhibitor of CYP2D6.

The use of Lexapro with tricyclic antidepressants, such as amitriptyline, may increase the risk of QT prolongation and serotonin syndrome. In general, this combination should be avoided.

The following list is not intended to be a complete list of drug interactions. It is best to consult your provider or pharmacist for a complete list.

Drug Drug class Wellbutrin Lexapro
Acalabrutinib
Dabrafenib
Erdafitinib
Gilteritinib
Ibrutinib
Antineoplastics Yes Yes
Almotriptan
Eletriptan
Oxitriptan
5HT Agonist / Triptans (antimigraine agents) No Yes
Dexmethylphenidate
Methylphenidate
Amphetamines No Yes
Alosetron
Ondansetron
Ramosetron
5HT3 Antagonists
(anti-nausea agents)
No Yes
Apixaban
Edoxaban
Antiplatelets No Yes
Aripiprazole Antipsychotic Yes Yes
Aspirin
Ibuprofen
Naproxen
Diclofenac
Nonsteroidal anti-inflammatory drugs (NSAIDS) No Yes
Atomoxetine Selective norepinephrine reuptake inhibitor (SNRI) Yes No
Bemiparin
Enoxaparin
Heparin
Anticoagulants No Yes
Bupropion Dopamine/ norepinephrine reuptake inhibitor No Yes
Buspirone Antianxiety No Yes
Carbamazepine Anticonvulsant Yes Yes
Enzalutamide Chemotherapy
agent
No Yes
Esomeprazole
Omeprazole
Proton pump inhibitor No Yes
Fluconazole Antifungal No Yes
Fluoxetine
Duloxetine
Paroxetine
Sertraline
SSRIs Yes Yes
Hydroxychloroquine Aminoquinolone/
Antimalarial
No Yes
Linezolid Antibiotic No Yes
Cyclobenzaprine
Metaxalone
Muscle relaxers No Yes
Pimozide Antipsychotic No Yes
Selegiline
Phenelzine
Rasagiline
Monoamine oxidase inhibitor (MAOI) No Yes
St. John’s Wort Herbal supplement No Yes
Hydrochlorothiazide
Chlorthalidone
Metolazone
Thiazide diuretics No Yes
Tramadol Opiate pain reliever Yes Yes
Amitriptyline
Clomipramine
Doxepin
Nortriptyline
Tricyclic antidepressants Yes Yes
Venlafaxine Selective norepinephrine reuptake inhibitor (SNRI) No Yes

Warnings of Wellbutrin and Lexapro

Patients with MDD may experience a worsening of depression or suicidal thoughts whether or not they are taking antidepressant medications. These conditions may worsen until remission is achieved. Wellbutrin and Lexapro therapy may increase suicidal ideation and thoughts among teens and young adults, especially in the early stages of treatment before any type of remission is achieved. These patients must be monitored closely if this treatment is deemed medically necessary. A therapy change may be necessary if symptoms suddenly arise or get worse.

Patients taking bupropion products for smoking cessation and who have no previous history of depression, may experience mental changes when they initiate therapy. These can include mood changes, hallucinations, paranoia, delusions, aggression, and anxiety. If this occurs, speak with your healthcare provider immediately.

In the case of both Wellbutrin and Lexapro, depression symptoms do not start to resolve immediately. Typically, changes in symptoms take a minimum of two weeks to observe, with most patients needing at least four to six weeks to see if the drug is having an impact on their symptoms.

Wellbutrin can increase the risk of seizure. This increased risk is dose-dependent, and the maximum total daily dose should not exceed 300 mg. Wellbutrin may also be responsible for increased cardiovascular events. Patients on Wellbutrin may experience increased blood pressure, leading to hypertension, even if they had no previous cardiovascular diagnoses.

Serotonin syndrome has been reported with all SSRIs, including Lexapro. This is a condition related to abnormally high levels of serotonin and can result in the patient feeling agitated, dizzy, and having an increased heart rate. This can be brought on by the use of two serotonergic drugs together. It is important to refer to the manufacturer’s information on drug interactions when prescribing these drugs.

Frequently asked questions about Wellbutrin vs. Lexapro

What is Wellbutrin?

Wellbutrin is a prescription antidepressant medication. It is a selective dopamine and norepinephrine reuptake inhibitor. It is prescribed in the treatment of major depressive disorder. The generic form, bupropion, is also approved in the treatment of smoking cessation in its sustained-release form (bupropion SR). Wellbutrin is available in immediate, sustained, and extended-release tablet formulations.

What is Lexapro?

Lexapro is a prescription antidepressant medication. It belongs to a class of medications known as selective serotonin reuptake inhibitors. It is prescribed to treat major depressive disorder, and it works by increasing available serotonin in the neuron synapse. Lexapro is available in 5 mg, 10 mg, and 20 mg strengths.

Are Wellbutrin and Lexapro the same?

While both Wellbutrin and Lexapro treat depression, they are not the same type of drug, Wellbutrin works by blocking the reuptake of dopamine and norepinephrine in the neuronal synapse, while Lexapro blocks the reuptake of serotonin. All of these neurotransmitters play a role in mood and affect.

Is Wellbutrin or Lexapro better?

In comparative studies, Wellbutrin and Lexapro provided similar rates of improvement in depression measurement scales. Wellbutrin may have fewer side effects, specifically related to libido, and therefore may be the better choice for some patients.

Can I use Wellbutrin or Lexapro while pregnant?

Wellbutrin is categorized as pregnancy category B by the Food and Drug Administration (FDA), meaning it is generally considered safe during pregnancy. Bupropion and its metabolites do cross the human placenta. Lexapro is pregnancy category C, meaning there have not been adequate human studies to determine efficacy. Animal studies have shown teratogenic effects on the fetus, including cardiovascular effects, and it has been determined that Lexapro crosses the human placenta. For these reasons, the use of Wellbutrin or Lexapro in pregnancy must be weighed against potential harm to the fetus.

Can I use Wellbutrin or Lexapro with alcohol?

Alcohol can increase the toxic effects of both Wellbutrin and Lexapro. Drinking alcohol while taking these drugs can cause significant psychomotor impairment, and for this reason, patients are advised to avoid alcohol if taking Wellbutrin or Lexapro. Alcohol specifically lowers the seizure threshold in patients taking Wellbutrin, and patients with a history of seizure should avoid this combination.

Can Wellbutrin help with anxiety?

Wellbutrin is not indicated in the treatment of anxiety, and in fact, for many patients, anxiety may worsen while on Wellbutrin. Patients with anxiety may benefit from other medication classes, and their healthcare professional may help them select the best agent.

How is Wellbutrin different from other antidepressants?

Wellbutrin specifically affects two neurotransmitters, dopamine, and norepinephrine. In addition to treating depression, the active ingredient in Wellbutrin has been proven to increase success in smoking cessation. It is also specifically indicated in seasonal affective disorder.

Is Wellbutrin similar to Adderall?

No, but both Wellbutrin and Adderall can play an important role in the treatment of ADHD. Adderall is a stimulant medication that has a long-standing history of success in ADHD. Wellbutrin, off-label, has been used to treat comorbid depression in patients with ADHD, with or without concurrent stimulant use.