What is the recommended dosage and treatment approach for Wellbutrin (bupropion) in adults with major depressive disorder, seasonal affective disorder, or anxiety disorders, particularly those with a history of substance use disorders or bipolar disorder?

Wellbutrin (Bupropion) in Mental Health: Clinical Recommendations

Primary Indication and First-Line Use

Bupropion is FDA-approved and recommended as a first-line pharmacologic treatment for major depressive disorder (MDD) and prevention of seasonal affective disorder (SAD), with particular advantages when sexual dysfunction or weight gain are concerns. 1, 2

Major Depressive Disorder Treatment Approach

• Start at 150 mg once daily (extended-release formulation), then increase to the usual target dose of 300 mg once daily after 4 days to minimize seizure risk while achieving therapeutic effect 1
• The American College of Physicians recommends selecting between cognitive behavioral therapy or second-generation antidepressants (including bupropion) after discussing treatment effects, adverse effects, cost, accessibility, and patient preferences 2
• Bupropion demonstrates efficacy comparable to SSRIs (fluoxetine, sertraline) and SNRIs (venlafaxine) for treating MDD 3, 4
• Reassess therapeutic response within 1-2 weeks of initiation and modify treatment if inadequate response occurs within 6-8 weeks 5

Seasonal Affective Disorder Protocol

• Initiate treatment in autumn prior to onset of seasonal depressive symptoms at 150 mg once daily 1
• Increase to 300 mg once daily after one week 1
• Continue treatment through the winter season, then discontinue 1
• Bupropion has the strongest evidence supporting long-term preventive use for recurrent SAD compared to other interventions 6

Key Clinical Advantages Over Other Antidepressants

Bupropion has the lowest rate of sexual adverse events among all second-generation antidepressants, significantly lower than fluoxetine, sertraline, and especially paroxetine 2, 7

• This makes bupropion the preferred switch option when SSRIs cause sexual dysfunction 7
• Associated with less somnolence and weight gain compared to tricyclic antidepressants 3, 4
• May be less likely to provoke mania than antidepressants with prominent serotonergic effects 8

Augmentation Strategy for Treatment-Resistant Depression

When SSRI monotherapy (particularly citalopram) produces inadequate response, adding bupropion-SR decreases depression severity more effectively than buspirone and causes fewer discontinuations due to adverse events 5, 7

• This augmentation approach is supported by moderate-quality evidence 5
• Consider this strategy before switching to a different antidepressant class 7

Use in ADHD (Second-Line Only)

Bupropion is explicitly a second-line agent for ADHD, to be considered only after all three stimulant classes have failed or caused intolerable side effects 5

• Stimulants remain the gold standard with 70-80% response rates and largest effect sizes from over 161 randomized controlled trials 5
• Bupropion shows more modest effects and requires 2-4 weeks for full effect, whereas stimulants work within days 5
• If ADHD symptoms improve on stimulants but depressive symptoms persist, add an SSRI rather than switching to bupropion alone 5

Critical Safety Considerations and Contraindications

Absolute Contraindications

Do not prescribe bupropion in patients with: 1

• Current or prior seizure disorder
• Current or prior diagnosis of bulimia or anorexia nervosa
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
• Concurrent MAOI use (allow 14-day washout period)

Seizure Risk Management

• The risk is dose-related; minimize by limiting daily dose to maximum 450 mg and gradually increasing the dose 1
• Discontinue immediately if seizure occurs 1
• Seizures are the predominant concern in overdose 8

Cardiovascular Monitoring

• Bupropion can increase blood pressure; monitor before initiating treatment and periodically during treatment 1, 5
• Cardiovascular effects are less pronounced compared to stimulants 5
• Monitor blood pressure and heart rate, particularly when combining with other antidepressants 7

Neuropsychiatric Adverse Events

• Increased risk of suicidal thinking and behavior in children, adolescents, and young adults; monitor closely for worsening depression and emergence of suicidal thoughts, especially during the first few months of treatment 1, 5
• Postmarketing reports include changes in mood (depression, mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic 1
• Instruct patients to discontinue and contact healthcare provider if such symptoms occur 1

Screening for Bipolar Disorder

• Screen patients for bipolar disorder before initiating bupropion and monitor for activation of mania/hypomania 1
• Lithium, valproate, and/or atypical antipsychotics remain standard first-line therapy for bipolar disorder, not bupropion 9
• FDA-approved treatments for bipolar depression include olanzapine-fluoxetine combination, not bupropion monotherapy 9

Special Populations and Dose Adjustments

Hepatic Impairment

• Moderate to severe hepatic impairment: 150 mg every other day 1, 5
• Mild hepatic impairment: Consider reducing dose and/or frequency 1, 5

Renal Impairment

• Consider reducing dose and/or frequency in patients with renal impairment 1, 5

Pregnancy

• Bupropion may be considered as an alternative to stimulants during pregnancy, but has been associated with a small increased risk of certain cardiovascular malformations with first-trimester exposure 5

Pediatric Use

• Bupropion has not been established as effective for pediatric depression, making it at best a second-line agent for ADHD in children 7

Common Adverse Effects

Most common adverse reactions (incidence ≥5%; ≥2× placebo rate) include: 1

• Dry mouth, nausea, insomnia, dizziness
• Pharyngitis, abdominal pain, agitation, anxiety, tremor
• Palpitation, sweating, tinnitus, myalgia
• Anorexia, urinary frequency, rash

Nervousness and insomnia are common; nausea appears slightly less common than with SSRIs 8

Drug Interactions

• Bupropion inhibits CYP2D6 and can increase concentrations of antidepressants (venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (haloperidol, risperidone, thioridazine), beta-blockers (metoprolol), and Type 1C antiarrhythmics 1
• CYP2B6 inducers (ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, phenytoin) may require dose increase, but should not exceed maximum recommended dose 1

Treatment Duration

• First episode of major depression requires at least 4 months of treatment 7
• Patients with recurrent depression benefit from prolonged maintenance therapy 7
• Periodically reassess the dose and need for maintenance treatment 1