What is the patient's response to bupropion (dopamine and norepinephrine reuptake inhibitor) in terms of mood improvement and smoking cessation, given her complex profile of depression, alcohol abuse, and insomnia, and initial ineffectiveness of Zoloft (sertraline, selective serotonin reuptake inhibitor)?

Critical Safety Assessment Required Before Continuing Bupropion

You must immediately assess whether bupropion has provided any mood improvement or smoking cessation benefit, because continuing this medication at any dose in a patient with alcohol abuse carries unacceptable seizure risk unless there is clear therapeutic benefit. 1

Immediate Clinical Decision Points

If Bupropion Shows NO Benefit:

• Discontinue bupropion immediately due to the significantly elevated seizure risk with alcohol abuse without offsetting therapeutic benefit 1
• The FDA label explicitly warns that "excessive use or abrupt discontinuation of alcohol" increases seizure risk, and this patient has active alcohol abuse 1
• Bupropion is contraindicated with "abrupt discontinuation of alcohol, benzodiazepines, barbiturates" 1

If Bupropion Shows Partial or Full Benefit:

For mood improvement: You have three evidence-based options:

1. Reduce bupropion to 150mg daily with morning-only dosing and have an urgent conversation about alcohol reduction, as the seizure threshold is dose-dependent (maximum 300mg daily, but lower with alcohol abuse) 1, 2

2. Switch to mirtazapine 15-45mg nightly, which addresses depression, insomnia, and has no increased seizure risk with alcohol 3, 2

   • Mirtazapine demonstrates faster onset of action (1-2 weeks vs 2-4 weeks for other antidepressants) 3, 2
   • Sedating properties directly address her insomnia 3, 2
   • No contraindication with alcohol use 2

3. Switch to a different SSRI (escitalopram or try fluoxetine), as the STAR*D trial showed 25% of SSRI non-responders achieve remission when switching to a different second-generation antidepressant 3

For smoking cessation benefit: If bupropion is helping with nicotine cravings:

• Mandatory dose reduction to 150mg daily with strict morning dosing to minimize insomnia 3, 1
• Document explicit discussion about alcohol reduction, as the combination creates "too high" seizure risk at 300mg 1
• Consider that limited data shows bupropion-naltrexone combinations reduce nicotine use, but this requires careful monitoring 3

Key Safety Considerations

Seizure Risk Factors Present in This Patient:

• Alcohol abuse (explicitly increases seizure threshold) 1
• Insomnia (may indicate alcohol withdrawal patterns) 1
• Dose above 150mg in the context of alcohol use 1

The FDA label states bupropion "can cause seizure" with "dose-related" risk, and specifically lists "excessive use of alcohol" and "abrupt discontinuation of alcohol" as conditions that "increase the risk of seizure" 1.

Neuropsychiatric Monitoring Required:

• Monitor for agitation, anxiety, panic attacks, hostility, aggressiveness, and suicidal ideation, especially during the first 1-2 weeks and with any dose changes 1
• The FDA mandates close monitoring as "changes may be abrupt" 1
• Bupropion carries a black box warning for suicidality in patients under 24 years, though risk decreases in older adults 1

Alternative Medication Profiles

Mirtazapine Advantages for This Patient:

• Addresses all three problems: depression, insomnia, and safer with alcohol 3, 2
• Antagonizes alpha-2 presynaptic receptors, enhancing norepinephrine and serotonin release 2
• 5-HT3 antagonism reduces nausea (unlike SSRIs) 2
• H1 receptor blockade provides sedation for insomnia 2
• Significant improvement within 1-2 weeks, with lower relapse rates at 40 weeks 2

SNRI Considerations (Venlafaxine/Duloxetine):

• May be superior to fluoxetine for anxiety symptoms 3
• However, venlafaxine has higher rates of nausea/vomiting than other SSRIs 3
• Weak evidence suggests venlafaxine may increase cardiovascular risk 3

Common Pitfalls to Avoid

• Never continue bupropion at 300mg with active alcohol abuse - this is explicitly contraindicated by mechanism 1
• Do not assume all SSRIs are equivalent - the American College of Physicians guidelines note that while second-generation antidepressants have similar efficacy, individual patient response varies significantly 3
• Do not overlook insomnia as a withdrawal symptom - this may indicate fluctuating alcohol use patterns that further increase seizure risk 1
• Avoid late-day dosing of any stimulating antidepressant in patients with insomnia 3, 1

3, 1, 2