What is Wellbutrin (bupropion) used for?

Wellbutrin (Bupropion) Uses and Applications

Wellbutrin (bupropion) is primarily indicated for the treatment of major depressive disorder (MDD) and smoking cessation, with additional applications in seasonal affective disorder (SAD) and off-label uses for attention deficit hyperactivity disorder (ADHD). 1, 2

Primary FDA-Approved Indications

• Major Depressive Disorder (MDD): Bupropion is an aminoketone antidepressant that works by inhibiting the reuptake of dopamine and norepinephrine, making it distinct from SSRIs as it has minimal effect on serotonin 1, 3
• Seasonal Affective Disorder (SAD): Bupropion XL is specifically approved for the prevention of seasonal affective disorder 1
• Smoking Cessation: Marketed as Zyban, bupropion is effective for smoking cessation with treatment typically beginning 1-2 weeks before the target quit date and continuing for 7-12 weeks 2

Mechanism of Action

• Bupropion acts primarily as a dopamine-norepinephrine reuptake inhibitor with minimal effect on serotonin, making it unique among antidepressants 3, 4
• It also acts as an inhibitor of nicotinic acetylcholinergic receptors, which contributes to its efficacy as a smoking cessation aid 2
• The medication is extensively metabolized into three active metabolites (hydroxybupropion, threohydrobupropion, and erythrohydrobuproprion), all with substantial antidepressant activity 4

Efficacy in Depression

• Bupropion has comparable efficacy to other antidepressants including SSRIs and some tricyclic antidepressants for treating major depression 5, 6
• The American College of Physicians recommends selecting second-generation antidepressants like bupropion based on adverse effect profiles, cost, and patient preferences rather than efficacy differences 2
• Treatment response should be assessed within 6-8 weeks, with modification recommended if adequate response is not achieved 2

Efficacy in Smoking Cessation

• A 2014 Cochrane review of 44 trials demonstrated bupropion's efficacy for smoking cessation with a relative risk of 1.62 compared to placebo 2
• The EAGLES trial (n=8,144) showed superior abstinence rates with bupropion compared to placebo (OR, 2.07) 2
• Bupropion may be particularly beneficial as a smoking cessation agent for persons with depression 2

Available Formulations

• Immediate Release (IR): Administered three times daily 5, 6
• Sustained Release (SR): Administered twice daily, typically 150 mg twice daily for depression and smoking cessation 7, 5
• Extended Release (XL): Administered once daily, typically 300 mg once daily in the morning 7, 5

Off-Label Uses

• Attention Deficit Hyperactivity Disorder (ADHD): Bupropion has shown efficacy in treating ADHD, though it's considered a second-line agent 2, 8
• Augmentation therapy: Can be used to augment partial response to SSRIs in depression treatment 3
• Bipolar depression: Some evidence supports its use in bipolar depression 8
• Sexual dysfunction: May help with hypoactive sexual desire disorder 8

Safety Considerations

• Seizure risk: Bupropion lowers the seizure threshold with a 0.1% seizure risk in clinical trials; should be avoided in patients with seizure disorders or brain metastases 2
• Drug interactions: Should not be combined with MAOIs or within 14 days of discontinuing MAOIs 7
• Common side effects: Include insomnia, dry mouth, headaches, nausea, and anxiety 3, 4
• Advantages over other antidepressants: Associated with lower rates of sexual dysfunction and weight gain compared to many other antidepressants 5, 6

Special Populations

• Patients with depression who want to quit smoking: Bupropion may be particularly beneficial for this population 2
• Hepatic/renal impairment: Dose adjustments are required; for moderate to severe hepatic impairment, total daily dose should not exceed 150 mg 7
• Older adults: Lower starting doses (approximately 50% of standard dose) are recommended 7

Bupropion offers a unique pharmacological profile among antidepressants with its focus on dopamine and norepinephrine rather than serotonin, making it valuable for patients who cannot tolerate or do not respond to SSRIs, particularly those concerned about sexual side effects or weight gain 3, 5.