When is Wellbutrin (bupropion) warranted?

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Last updated: June 24, 2025View editorial policy

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From the Guidelines

Wellbutrin (bupropion) is warranted primarily for treating major depressive disorder and as an aid for smoking cessation, particularly when patients have not responded well to other antidepressants or experience fatigue, low energy, or decreased motivation as prominent symptoms of their depression. It's typically prescribed when patients cannot tolerate the sexual side effects or weight gain associated with SSRIs 1. The usual starting dose is 150 mg once daily for 3-4 days, often increasing to 150 mg twice daily, with a maximum dose of 450 mg daily divided into multiple doses. For smoking cessation (under the brand name Zyban), treatment typically begins 1-2 weeks before the quit date at 150 mg daily for 3 days, then 150 mg twice daily for 7-12 weeks. Wellbutrin works differently from most antidepressants by primarily affecting dopamine and norepinephrine rather than serotonin, which explains its energizing effects and lower impact on sexual function 1.

Key Considerations

  • Bupropion is associated with a lower rate of sexual adverse events than fluoxetine or sertraline, whereas paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline 1.
  • SSRIs are associated with an increased risk for suicide attempts compared with placebo, and patients should be monitored for rare but serious side effects including agitation, insomnia, and potential suicidal thoughts, particularly when starting treatment 1.
  • It should be avoided in patients with seizure disorders, eating disorders, or those undergoing abrupt alcohol or sedative withdrawal due to a slightly increased seizure risk 1.

Monitoring and Follow-Up

  • Clinicians should assess patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis beginning within 1 to 2 weeks of initiation of therapy 1.
  • The U.S. Food and Drug Administration advises that all patients receiving antidepressants be closely monitored on a regular basis for increases in suicidal thoughts and behaviors, particularly during the first 1 to 2 months of treatment 1.

From the FDA Drug Label

The efficacy of bupropion in the treatment of major depressive disorder was established with the immediate-release formulation of bupropion hydrochloride in two 4-week, placebo-controlled trials in adult inpatients with MDD and in one 6-week, placebo-controlled trial in adult outpatients with MDD The efficacy of bupropion hydrochloride extended-release tablets (XL) in the prevention of seasonal major depressive episodes associated with SAD was established in 3 randomized, double-blind, placebo-controlled trials in adult outpatients with a history of MDD with an autumn-winter seasonal pattern (as defined by DSM-IV criteria)

Wellbutrin (bupropion) is warranted for the treatment of:

  • Major Depressive Disorder (MDD): as established by two 4-week and one 6-week placebo-controlled trials in adult inpatients and outpatients with MDD 2
  • Seasonal Affective Disorder (SAD): as established by three randomized, double-blind, placebo-controlled trials in adult outpatients with a history of MDD with an autumn-winter seasonal pattern 2

From the Research

Indications for Wellbutrin (Bupropion)

Wellbutrin (bupropion) is warranted for the treatment of:

  • Major depressive disorder (MDD) 3, 4, 5
  • Seasonal affective disorder (SAD) 3, 4, 5
  • Smoking cessation 3, 5
  • Attention deficit hyperactivity disorder (ADHD) 3, 6

Off-Label Uses

Wellbutrin (bupropion) may also be used off-label for:

  • Augmenting a partial response to selective serotonin reuptake inhibitor antidepressants 5
  • Helping people quit tobacco smoking 3, 5
  • Reducing fatigue in cancer 5
  • Reducing concentration problems 5

Important Considerations

When prescribing Wellbutrin (bupropion), it is essential to consider the following:

  • Potential for seizures, especially at high doses 7
  • Risk of cardiovascular issues 7
  • Inhibitory effects on cytochrome P450-2D6 (CYP2D6), which may lead to clinically-relevant drug interactions 3, 5
  • Common side effects, such as nervousness, insomnia, nausea, and sexual dysfunction 3, 6, 4, 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Bupropion.

Drugs of today (Barcelona, Spain : 1998), 2006

Research

Bupropion: pharmacology and therapeutic applications.

Expert review of neurotherapeutics, 2006

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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