FDA-Approved Indications for Wellbutrin (Bupropion)
Wellbutrin (bupropion) is FDA-approved for two primary indications: treatment of major depressive disorder (MDD) and prevention of seasonal affective disorder (SAD). 1
Primary FDA-Approved Indications
Major Depressive Disorder (MDD)
- Bupropion hydrochloride extended-release tablets are indicated for the treatment of major depressive disorder as defined by the Diagnostic and Statistical Manual (DSM). 1
- The efficacy was established through multiple controlled trials: two 4-week inpatient trials, one 6-week outpatient trial, and a long-term maintenance trial (up to 44 weeks) demonstrating sustained efficacy. 1
- The recommended starting dose is 150 mg once daily in the morning, increasing to the target dose of 300 mg once daily after 4 days. 1
Seasonal Affective Disorder (SAD)
- Bupropion is indicated specifically for the prevention of seasonal major depressive episodes in patients with a diagnosis of SAD. 1
- Efficacy was established in 3 placebo-controlled trials in adult outpatients with a history of MDD with an autumn-winter seasonal pattern. 1
- Treatment should be initiated in the autumn, prior to the onset of depressive symptoms, continued through the winter season, then tapered and discontinued in early spring. 1
- The recommended starting dose is 150 mg once daily, with potential increase to 300 mg once daily after 7 days. 1
Off-Label Uses Supported by Evidence
Smoking Cessation
- While the immediate-release and sustained-release formulations of bupropion are FDA-approved for smoking cessation, the extended-release (XL) formulation discussed here is not specifically FDA-approved for this indication. 2, 3
- For smoking cessation, the standard dosing is 150 mg twice daily (300 mg total) of the SR formulation, beginning 1-2 weeks before the target quit date, with typical treatment duration of 7-12 weeks. 2, 3
- Bupropion achieves abstinence rates approximately 9-10 percentage points above placebo when combined with intensive behavioral support. 3
- This may be particularly beneficial for patients with comorbid depression who want to quit smoking, addressing both conditions simultaneously. 3
Augmentation Strategy for Treatment-Resistant Depression
- When initial SSRI monotherapy fails after 6-8 weeks, augmenting with bupropion is a well-established strategy. 2, 3
- Low-quality evidence demonstrates that augmenting SSRIs with bupropion decreases depression severity more effectively than augmentation with buspirone. 2, 3
- Bupropion augmentation showed significantly lower discontinuation rates due to adverse events (12.5%) compared to buspirone (20.6%). 3
Combination Products
Naltrexone-Bupropion for Weight Management
- The combination product naltrexone-bupropion XL is FDA-approved as an adjunct to reduced-calorie diet and increased physical activity for chronic weight management in adults with BMI ≥30 kg/m² (obesity) or BMI ≥27 kg/m² (overweight) with at least one weight-related comorbidity. 4
- This is a distinct indication from bupropion monotherapy and requires specific dosing titration. 4
- This combination is absolutely contraindicated in patients requiring opioid therapy, those with uncontrolled hypertension, and those with seizure disorders. 4
Critical Contraindications Across All Indications
Bupropion is contraindicated in the following situations: 1
- Seizure disorder or any condition that predisposes to seizures 1
- Current or prior diagnosis of bulimia or anorexia nervosa 1
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1
- Concurrent use with MAOIs or within 14 days of discontinuing MAOIs 1
- Known hypersensitivity to bupropion 1
Special Population Dosing Adjustments
Hepatic Impairment
- For moderate to severe hepatic impairment (Child-Pugh score 7-15), the maximum dose is 150 mg every other day. 1
- For mild hepatic impairment (Child-Pugh score 5-6), consider reducing the dose and/or frequency. 1
Renal Impairment
- For moderate to severe renal impairment (GFR <90 mL/min), reduce the total daily dose by half. 3
- Consider reducing dose and/or frequency in any patient with renal impairment. 1
Important Safety Warnings
Black Box Warning
- Bupropion carries an FDA black box warning for increased risk of suicidal thoughts and behavior in children, adolescents, and young adults (under age 24) taking antidepressants. 1
- Monitor closely for worsening depression and emergence of suicidal thoughts, especially during the first 1-2 months of treatment when suicide risk is greatest. 3, 1