What are the guidelines for prescribing Wellbutrin (bupropion) to adults or geriatric individuals with major depressive disorder or seasonal affective disorder?

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

Initial Prescribing Recommendation

When prescribing bupropion for major depressive disorder or seasonal affective disorder, start with 150 mg once daily and increase to the usual target dose of 300 mg once daily after 4-7 days, with dose selection based primarily on adverse effect profile, cost, and patient preference rather than superior efficacy over other second-generation antidepressants. 1, 2

Indications and Evidence Base

Major Depressive Disorder

• Bupropion is FDA-approved for treatment of major depressive disorder with established efficacy in multiple placebo-controlled trials 2
• The American College of Physicians recommends selecting second-generation antidepressants based on adverse effect profiles, cost, and patient preferences, as no second-generation antidepressant demonstrates superior efficacy over another 1
• Bupropion demonstrated efficacy at 450 mg/day in fixed-dose trials, with 78% of patients effectively treated at 300-450 mg/day 2
• A maintenance trial showed significantly lower relapse rates over 44 weeks compared to placebo in patients with recurrent MDD 2

Seasonal Affective Disorder

• Bupropion XL is FDA-approved for prevention of seasonal major depressive episodes in patients with autumn-winter seasonal pattern 2
• Three randomized controlled trials demonstrated depression-free rates of 84.3% versus 72.0% for bupropion versus placebo 2
• Treatment should be initiated in autumn (September-November) prior to symptom onset and continued through winter season with a 2-week taper beginning in the fourth week of March 2

Dosing Algorithm

Major Depressive Disorder

• Starting dose: 150 mg once daily 2
• Target dose: 300 mg once daily, may increase after 4 days 2
• Maximum dose: 450 mg once daily (do not exceed to minimize seizure risk) 2
• Increase dose gradually to reduce seizure risk 2

Seasonal Affective Disorder

• Starting dose: 150 mg once daily 2
• Target dose: 300 mg once daily, may increase after 1 week 2
• Duration: Approximately 4-6 months (autumn through early spring) 2
• Discontinue with 2-week taper beginning fourth week of March 2

Special Populations

• Moderate to severe hepatic impairment: 150 mg every other day 2
• Mild hepatic impairment: Consider reducing dose and/or frequency 2
• Renal impairment: Consider reducing dose and/or frequency 2
• Geriatric patients: Bupropion is a preferred agent for older adults with depression 1

Monitoring Requirements

Initial Monitoring (Critical Period)

• Begin monitoring within 1-2 weeks of initiation for suicidal thoughts, behaviors, agitation, irritability, or unusual behavioral changes 1, 2
• The FDA mandates close monitoring for increases in suicidal ideation, particularly during the first 1-2 months when risk for suicide attempts is greatest 1, 2
• Assess therapeutic response and adverse effects regularly starting within 1-2 weeks 1

Response Assessment Timeline

• Modify treatment if inadequate response within 6-8 weeks of initiation 1
• The American College of Physicians emphasizes that trying a different evidence-based approach is more important than which specific strategy is chosen 3

Blood Pressure Monitoring

• Monitor blood pressure before initiating treatment and periodically during treatment, as bupropion can increase blood pressure 2

Absolute Contraindications

Do not prescribe bupropion in patients with: 2

• Current or prior diagnosis of seizure disorder
• Current or prior diagnosis of bulimia or anorexia nervosa (increased seizure risk)
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
• Concurrent MAOI use or within 14 days of stopping MAOI
• Known hypersensitivity to bupropion

Key Advantages Over Other Antidepressants

Sexual Function

• Bupropion is associated with significantly lower rates of sexual adverse events than fluoxetine, sertraline, and paroxetine 1
• This makes it particularly valuable for patients concerned about sexual dysfunction or those who experienced sexual side effects with SSRIs 1

Weight and Sedation

• Associated with less somnolence and weight gain compared to tricyclic antidepressants 4, 5
• Less somnolence compared to SSRIs 4, 5

Mechanism of Action

• Presumed dopamine-norepinephrine reuptake inhibitor, offering a different mechanism than SSRIs 4, 5, 6
• May be less likely to provoke mania than antidepressants with prominent serotonergic effects 6

Common Adverse Effects

Most common adverse reactions (≥5% incidence, ≥2× placebo): 2

• Dry mouth, nausea, insomnia, dizziness
• Pharyngitis, abdominal pain, agitation, anxiety
• Tremor, palpitation, sweating, tinnitus
• Myalgia, anorexia, urinary frequency, rash

Nervousness and insomnia are the most characteristic side effects 6

Critical Safety Warnings

Seizure Risk (Dose-Dependent)

• The risk of seizures is directly dose-related and can be minimized by not exceeding 450 mg daily and gradually increasing the dose 2
• Discontinue immediately if seizure occurs 2
• Bupropion doses of 2.7g and upward can lead to seizures, encephalopathy, and cardiovascular effects in overdose 7

Neuropsychiatric Events

• Postmarketing reports include changes in mood (depression, mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, panic, suicidal ideation, suicide attempt, and completed suicide 2
• Instruct patients to discontinue bupropion and contact healthcare provider immediately if such symptoms occur 2

Activation of Mania/Hypomania

• Screen patients for bipolar disorder before initiating treatment 2
• Monitor for manic symptoms during treatment 2

Angle-Closure Glaucoma

• Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants 2

Drug Interactions

CYP2B6 Inducers

• Dose increase may be necessary if coadministered with CYP2B6 inducers (ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, phenytoin), but should not exceed maximum recommended dose 2

CYP2D6 Inhibition

• Bupropion has inhibitory effects on CYP2D6, raising concern for clinically-relevant drug interactions 6

Contraindicated Combinations

• Never combine with MAOIs (14-day washout required) 2
• Do not start in patients receiving linezolid or intravenous methylene blue 2

Treatment Duration

First Episode

• Continue treatment for at least 4 months after achieving satisfactory response 1, 3

Recurrent Depression

• Patients with 2 or more prior depressive episodes may benefit from prolonged treatment (4-9 months or longer) 3
• Maintenance trial data supports continued treatment to prevent relapse 2

Periodic Reassessment

• Periodically reassess the dose and need for maintenance treatment 2

Augmentation Strategy for Treatment-Resistant Depression

• Low-quality evidence from the STAR*D trial showed no difference in response when augmenting citalopram with bupropion compared to buspirone 3
• Bupropion is useful in augmenting partial response to SSRI antidepressants 6
• The American College of Physicians notes that augmenting with another antidepressant shows no significant difference in response rates compared to other augmentation strategies 3

Common Prescribing Pitfalls to Avoid

Exceeding Maximum Dose

• Never exceed 450 mg daily due to dose-dependent seizure risk 2
• Gradual dose escalation is mandatory 2

Inadequate Monitoring

• Failing to monitor for suicidal ideation in the first 1-2 weeks is a critical error, as this is when risk is highest 1, 2

Prescribing to High-Risk Patients

• Do not prescribe to patients with eating disorders (bulimia/anorexia) due to significantly increased seizure risk 2
• Evaluate patients with cardiovascular issues and seizure history before starting or increasing dosage 7

Abrupt Discontinuation

• Taper over 2 weeks when discontinuing, particularly for seasonal affective disorder treatment 2

Ignoring Hepatic/Renal Impairment

• Failure to adjust dosing in hepatic or renal impairment increases risk of adverse effects 2