What is Bupropion (Bupron)?

What is Bupropion (Bupron)?

Bupropion is an atypical antidepressant that functions as a norepinephrine and dopamine reuptake inhibitor, FDA-approved for treating major depressive disorder and as a smoking cessation aid. 1

Mechanism of Action

Bupropion is chemically unrelated to tricyclic antidepressants, SSRIs, or other conventional antidepressants—it belongs to the aminoketone class. 1 Unlike virtually all other antidepressants available in the United States, bupropion has no appreciable activity on serotonin neurotransmission. 2 Instead, it:

• Inhibits reuptake of norepinephrine and dopamine in the central nervous system 2, 3
• Acts as an inhibitor of nicotinic acetylcholinergic receptors, which explains its efficacy for smoking cessation 4
• Produces three active metabolites (hydroxybupropion, threohydrobupropion, and erythrohydrobupropion) that contribute substantially to its antidepressant activity 2

FDA-Approved Indications

Bupropion has two primary FDA-approved uses:

1. Major depressive disorder - Originally approved as an antidepressant 4, 1
2. Smoking cessation - The first non-nicotine medication licensed for this purpose 5

Available Formulations

Bupropion comes in three oral formulations, all bioequivalent in terms of systemic exposure: 3

• Immediate Release (IR): Administered three times daily 3
• Sustained Release (SR): Administered twice daily, typically 150 mg twice daily (300 mg total) 6, 3
• Extended Release (XL): Administered once daily, typically 300 mg in the morning 6, 3

Dosing Protocols

For Major Depressive Disorder:

• Start with 150 mg once daily for 3 days, then increase to 150 mg twice daily (SR formulation) 6
• Maximum dose: 450 mg per day (XL formulation) or 400 mg per day (SR formulation) to minimize seizure risk 6, 2

For Smoking Cessation:

• Begin 1-2 weeks before the target quit date to establish therapeutic drug levels 6, 7
• Dosing: 150 mg once daily for 3 days, then 150 mg twice daily (300 mg total) 7
• Treatment duration: 7-12 weeks, with efficacy assessed after this period 7
• May extend to 6-12 months in successful quitters to prevent relapse 7

Clinical Efficacy

Depression:

• Comparable efficacy to SSRIs and tricyclic antidepressants in treating major depressive disorder 3, 8
• Onset of action: 2 weeks, with full efficacy at 4 weeks 2
• Particularly beneficial for patients with comorbid depression and nicotine dependence, addressing both conditions simultaneously 9, 4

Smoking Cessation:

• Superior abstinence rates compared to placebo (OR 2.07; 95% CI 1.75-2.45) 9
• Similar efficacy to nicotine patch but less effective than varenicline 9
• May be especially beneficial for smokers with depression history 9, 7

Critical Safety Concerns

Seizure Risk (Most Serious):

• Seizure incidence: 0.1% with proper dosing 4
• Bupropion lowers the seizure threshold and must be gradually titrated 2
• Contraindicated in patients with: 7, 1
  • Current or prior seizure disorder
  • Brain metastases or CNS tumors
  • Eating disorders (anorexia nervosa or bulimia)
  • Abrupt discontinuation of alcohol or sedatives

Other Contraindications:

• MAOI use within 14 days (allow 2-week washout period) 1
• Concurrent tamoxifen use 6
• Closed-angle glaucoma 7

Common Side Effects:

• Disturbed sleep, dry mouth, headaches, nausea 9, 7
• Agitation, constipation, tremor 2
• Notably causes less sexual dysfunction and weight gain compared to SSRIs 3, 8

Monitoring Requirements:

• Neuropsychiatric symptoms (depression, suicidal ideation), especially in patients under 24 years 6, 7
• Blood pressure monitoring - can cause hypertension, particularly when combined with nicotine replacement therapy 1
• Evaluate response after 4 weeks of treatment 7

Special Population Considerations

Hepatic Impairment:

• Maximum 150 mg daily for moderate to severe hepatic impairment 6

Renal Impairment:

• Reduce total daily dose by half for moderate to severe renal impairment (GFR <90 mL/min), as bupropion metabolites accumulate 6

Older Adults:

• Start with 37.5 mg every morning, gradually increasing by 37.5 mg every 3 days 6
• Maximum 300 mg total daily (150 mg twice daily) 6
• Administer second dose before 3 p.m. to minimize insomnia 6

Pregnancy and Breastfeeding:

• Passes into breast milk - discuss risks/benefits with patients 1
• Pregnancy registry available at 1-844-405-6185 1

Clinical Advantages

Bupropion offers distinct advantages over other antidepressants:

• No sexual dysfunction - a major advantage over SSRIs 3, 8
• Weight loss rather than weight gain 2, 8
• Dual benefit for depression and smoking cessation 4, 5
• Can be used as augmentation therapy when SSRIs fail, with superior efficacy compared to buspirone 4

Key Clinical Pearls

• The insoluble shell of XL tablets may appear intact in stool - this is normal and does not indicate malabsorption 1
• Longer treatment duration helps prevent relapse in successful quitters 9
• Combination with NRT shows mixed evidence for superior efficacy, though it increases hypertension risk 9, 1
• Highly nicotine-dependent smokers may experience rebound depression when bupropion is discontinued 10