How should Wellbutrin (bupropion) be prescribed to an adult patient with major depressive disorder or seasonal affective disorder?

Prescribing Wellbutrin (Bupropion) for Major Depressive Disorder and Seasonal Affective Disorder

For major depressive disorder, start bupropion extended-release (XL) at 150 mg once daily in the morning for 4 days, then increase to the target dose of 300 mg once daily, and for seasonal affective disorder, start at 150 mg daily for 7 days before increasing to 300 mg daily, initiating treatment in autumn before symptom onset and continuing through winter with a spring taper. 1

Dosing Protocol for Major Depressive Disorder

Initial dosing:

• Begin with 150 mg XL once daily in the morning 1
• After 4 days, increase to the target dose of 300 mg once daily 1
• Administer in the morning, with or without food 1
• Swallow tablets whole—never crush, divide, or chew 1

Duration of treatment:

• Continue for several months beyond acute response 1
• For first episode: maintain for 4-9 months after achieving satisfactory response 2
• For two or more prior episodes: consider years to lifelong maintenance therapy 2
• Maintain the same dosage that achieved remission during continuation phase to prevent relapse 2

Dosing Protocol for Seasonal Affective Disorder

Timing and dosing:

• Initiate in autumn (September to November) prior to symptom onset 1
• Start at 150 mg once daily for 7 days 1
• Increase to target dose of 300 mg once daily after first week 1
• Continue through winter season (approximately 4-6 months for most patients) 1

Discontinuation protocol:

• Taper in early spring (fourth week of March) 1
• For patients on 300 mg daily, decrease to 150 mg once daily before discontinuing 1
• Use a 2-week taper period 1

Evidence of efficacy:

• Three placebo-controlled trials demonstrated depression-free rates of 84.3% with bupropion versus 72.0% with placebo 1
• Individual trial results showed 81.4% vs. 69.7%, 87.2% vs. 78.7%, and 84.0% vs. 69.0% depression-free rates 1
• Bupropion has the strongest evidence supporting long-term preventive use for seasonal affective disorder 3

Critical Monitoring Requirements

Suicidality monitoring (highest priority):

• Monitor intensively for suicidal thoughts and behaviors, particularly during the first 1-2 months of treatment 2, 1
• Assess at 1-2 week intervals initially 2
• Antidepressants increase risk of suicidal thoughts in children, adolescents, and young adults (no increased risk in patients ≥65 years) 1
• Advise families and caregivers of the need for close observation 1

Behavioral changes:

• Watch for agitation, irritability, or unusual behavioral changes indicating worsening depression 2
• Monitor for emergence of activation symptoms that could signal treatment failure 2

Seizure risk:

• Increase dose gradually to minimize seizure risk 1
• Bupropion doses of 2.7g and upward can lead to seizures, encephalopathy, and cardiovascular effects 4
• Evaluate patients with increased cardiovascular risk and seizure history before starting or increasing dosage 4

Delayed hypersensitivity reactions:

• Recognize that delayed allergic reactions can appear 2 or more weeks after initiation 5
• Monitor for pruritus and urticaria, particularly in males aged 17-40 years with history of allergic reactions 5
• If hypersensitivity develops, taper over 7 days and consider alternative antidepressant 5

Dosage Adjustments for Special Populations

Hepatic impairment:

• Moderate to severe (Child-Pugh 7-15): maximum dose 150 mg every other day 1
• Mild (Child-Pugh 5-6): consider reducing dose and/or frequency 1

Renal impairment:

• For GFR <90 mL/min: consider reducing dose and/or frequency 1

Efficacy Evidence

Major depressive disorder:

• Established efficacy in two 4-week inpatient trials and one 6-week outpatient trial 1
• 450 mg daily dose showed significant efficacy on HAMD total score and CGI-S 1
• Long-term trial demonstrated significantly lower relapse rates over 44 weeks compared to placebo 1

Mechanism and advantages:

• Inhibits presynaptic dopamine and norepinephrine reuptake 6
• Significantly lower rates of sexual dysfunction compared to SSRIs 2, 6
• Less likely to provoke mania than serotonergic antidepressants 6
• Effective for augmenting partial SSRI response, with bupropion outperforming buspirone for depression severity reduction 2

Common Pitfalls to Avoid

• Do not wait indefinitely for response: Modify treatment if inadequate response occurs within 6-8 weeks 2
• Do not discontinue abruptly: Always taper from 300 mg to 150 mg before stopping 1
• Do not combine with MAOIs: Contraindicated due to serotonin syndrome risk 7
• Do not overlook drug interactions: Bupropion inhibits CYP2D6 and may affect medications metabolized by this pathway 6
• Do not expect immediate results: Allow adequate time (6-8 weeks) to assess efficacy 2
• Do not crush or divide tablets: This alters the extended-release properties and increases seizure risk 1