What medication should be started for a 59-year-old patient with depression and anxiety, taking Prozac (fluoxetine), with increased symptoms after smoking cessation?

Augment Fluoxetine with Bupropion SR 150mg Twice Daily for Post-Smoking Cessation Depression and Anxiety

For this 59-year-old patient with worsening depression and anxiety after smoking cessation while on fluoxetine, add bupropion SR starting at 150mg once daily for 3 days, then increase to 150mg twice daily (300mg total daily dose). This addresses both the increased depressive symptoms and supports smoking cessation maintenance simultaneously 1, 2.

Rationale for Bupropion Augmentation

Augmenting SSRIs with bupropion decreases depression severity more effectively than other augmentation strategies like buspirone, with significantly lower discontinuation rates due to adverse events (12.5% vs 20.6%, p<0.001) 1. This combination is particularly advantageous because:

• Bupropion addresses depression through complementary noradrenergic/dopaminergic pathways while fluoxetine works via serotonin 1
• The combination specifically benefits patients with comorbid depression and recent smoking cessation, addressing both conditions simultaneously 1, 2
• Bupropion helps prevent relapse to smoking during the vulnerable post-cessation period when depressive symptoms often worsen 3, 4

Specific Dosing Protocol

Start bupropion SR 150mg every morning for days 1-3, then increase to 150mg twice daily if tolerated 1. Critical timing considerations:

• Administer the first dose in the morning to leverage activating properties 1
• Give the second dose before 3 PM to minimize insomnia risk 1
• Maximum daily dose must not exceed 300mg for smoking cessation to maintain seizure risk at 0.1% 1

Pre-Treatment Safety Screening Required

Before prescribing bupropion, screen for absolute contraindications 1, 5:

• Seizure history or conditions predisposing to seizures (stroke, brain metastases, head trauma) 3, 1
• Current or recent MAOI use (within 14 days) 3, 1
• Eating disorders (bulimia or anorexia nervosa) due to increased seizure risk 1
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs 1
• Uncontrolled hypertension - bupropion can elevate blood pressure 1, 5
• Moderate to severe hepatic or renal impairment requiring dose reduction 1, 6

Monitoring Parameters

Monitor closely within 1-2 weeks of initiation and throughout treatment 1:

• Blood pressure and heart rate periodically, especially first 12 weeks, as bupropion can cause elevations 1, 5
• Neuropsychiatric symptoms including agitation, anxiety worsening, hostility, or suicidal ideation, particularly in patients under 24 years 1, 5
• Seizure risk factors - both fluoxetine and bupropion can lower seizure threshold 1

The FDA black box warning emphasizes increased risk of suicidal thoughts and behavior in younger patients with depression, requiring close monitoring especially during the first few months 1.

Expected Timeline for Response

Allow 6-8 weeks at adequate dose before determining treatment response 1. However:

• Energy levels and apathy may improve within the first few weeks due to bupropion's activating properties 1
• Smoking cessation support continues for 7-12 weeks after the quit date 1
• If no adequate response by 6-8 weeks, consider further treatment modification 1

Addressing the Anxiety Component

While bupropion's stimulating properties can theoretically provoke anxiety, clinical trials suggest it may reduce anxiety symptoms in depressed patients, showing comparable efficacy to SSRIs in mild to moderate anxiety 7. The key is:

• Starting at lower doses (150mg once daily initially) and monitoring for anxiogenic symptoms 7
• Recognizing that patients with higher baseline anxiety scores actually responded better to bupropion treatment at 6 months in smoking cessation trials 8
• The combination with fluoxetine provides serotonergic coverage for anxiety while bupropion addresses energy and smoking cessation 1

Additional Clinical Benefits

Beyond addressing depression and smoking cessation, this combination offers 1, 2:

• Minimal weight gain or even weight loss - important post-smoking cessation when weight gain is common
• Potential improvement in SSRI-associated sexual dysfunction (16% of patients reported spontaneous improvement) 2
• No evidence of emergent depression when bupropion is added to SSRI maintenance treatment 2

Critical Safety Considerations

The combination of fluoxetine and bupropion does not have significant pharmacokinetic interactions that would preclude their use together, but both medications can lower seizure threshold, so adherence to maximum dosing guidelines is essential 1. The seizure risk with bupropion at 300mg/day is approximately 0.1% (1 in 1,000) 1.

Do not exceed 300mg daily total dose for this indication to maintain acceptable seizure risk 3, 1.