What is considered before initiating Wellbutrin (bupropion) for depression?

What Should Be Considered Before Initiating Wellbutrin (Bupropion) for Depression?

Before starting Wellbutrin for depression, you must screen for seizure risk factors, bipolar disorder history, and cardiovascular disease, as these represent absolute or relative contraindications that fundamentally alter treatment decisions.

Critical Pre-Treatment Screening

Seizure Risk Assessment (Absolute Priority)

• Screen for any history of seizure disorder, eating disorders (anorexia or bulimia nervosa), or conditions that lower seizure threshold 1, 2
• Identify patients with abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs—this is an absolute contraindication 3
• Bupropion lowers the convulsive threshold and should not be used in patients predisposed to seizures 2
• The seizure rate is comparable to other antidepressants only when dosage is maintained at 450 mg/day or less in divided doses 2

Bipolar Disorder Screening (Essential)

• Obtain detailed personal and family history of bipolar disorder, mania, hypomania, or suicide before initiating bupropion 1
• Screen specifically for prior manic or hypomanic episodes, as antidepressant treatment can precipitate manic episodes 1
• While bupropion may have lower risk of inducing mania compared to other antidepressants, this risk increases significantly at doses exceeding 450 mg/day 4, 5
• Bupropion is not approved for treatment of bipolar depression 1

Cardiovascular Evaluation

• Assess for uncontrolled hypertension, recent myocardial infarction, or unstable cardiac disease 1, 6
• Measure baseline blood pressure and heart rate, as bupropion can cause elevations in both 1
• In patients with pre-existing hypertension, bupropion may exacerbate blood pressure control—two patients in clinical trials discontinued due to hypertension exacerbation 1, 6
• While bupropion has a favorable cardiac profile compared to tricyclics (minimal conduction delay and orthostatic hypotension), it can cause supine blood pressure elevation 6

Medication Reconciliation

Absolute Contraindications

• Verify patient is not taking MAO inhibitors or has not taken them within the past 14 days 1
• Confirm patient is not currently taking opioid medications if considering naltrexone-bupropion combination 7
• Check for concurrent tamoxifen use, as bupropion inhibits CYP2D6 and may reduce tamoxifen efficacy 3

Drug Interactions Requiring Caution

• Identify all medications metabolized by CYP2D6 (including SSRIs like paroxetine, fluoxetine, sertraline; tricyclics; antipsychotics like risperidone; beta-blockers) as bupropion may increase their levels 1
• Screen for dopaminergic drugs (levodopa, amantadine) as combination with bupropion can cause CNS toxicity including restlessness, agitation, tremor, and ataxia 1
• Assess for other medications that lower seizure threshold (antipsychotics, other antidepressants, theophylline, systemic corticosteroids) 1

Hepatic and Renal Function Assessment

• Obtain baseline liver function tests, particularly in patients with suspected hepatic impairment 3
• For moderate to severe hepatic impairment, maximum dose must not exceed 150 mg daily 3
• Check renal function (GFR)—if GFR <90 mL/min, reduce total daily dose by half 3

Special Population Considerations

Older Adults

• Plan to start with lower doses (37.5 mg every morning) and titrate slowly by 37.5 mg every 3 days 3
• Maximum dose for older adults is 150 mg twice daily (300 mg total) 3

Women of Childbearing Potential

• Discuss pregnancy plans and contraception, as data on bupropion in pregnancy are limited 1
• Consider enrollment in the National Pregnancy Registry for Antidepressants if pregnancy occurs 1

Clinical Profile Assessment

Ideal Candidates for Bupropion

• Patients with depression characterized by low energy, apathy, or hypersomnia benefit from bupropion's activating properties 3
• Patients concerned about sexual dysfunction or weight gain, as bupropion has lower rates of these side effects compared to SSRIs 3
• Patients attempting smoking cessation, as bupropion addresses both depression and nicotine dependence 7, 3

Patients Requiring Alternative Agents

• Those with significant anxiety or insomnia as primary symptoms, since bupropion is activating and must be dosed before 3 PM to minimize insomnia 3
• Patients with psychotic features require concurrent antipsychotic medication 3
• Those with alcohol use disorder should minimize or avoid alcohol consumption during treatment 1

Baseline Monitoring Parameters

• Blood pressure and heart rate (to be monitored periodically during treatment, especially first 12 weeks) 7
• Mental status examination focusing on suicidal ideation, particularly in patients under 24 years old who require close monitoring for increased suicidal thoughts 7
• Document baseline depression severity using standardized scales to assess treatment response after 6-8 weeks 3

Patient Education Before Initiation

• Counsel about seizure risk and the importance of not exceeding maximum daily dose of 450 mg 3, 1
• Warn about potential for allergic reactions (pruritus, urticaria, angioedema, dyspnea) requiring immediate discontinuation 1
• Advise about timing of doses (morning and before 3 PM) to minimize insomnia 3
• Discuss the 6-8 week timeframe needed to assess full therapeutic response, though energy improvements may occur within first few weeks 3