What is the appropriate management for a 22‑year‑old man with depressive symptoms who wants to quit smoking and is currently taking buspirone 7.5 mg daily?

Management of Depression and Smoking Cessation in a 22-Year-Old on Buspirone

For this 22-year-old man with depression who wants to quit smoking and is currently on buspirone 7.5 mg daily, you should discontinue buspirone (which is ineffective for both depression and smoking cessation), initiate bupropion SR 150 mg once daily for 3 days then increase to 150 mg twice daily, and combine it with behavioral counseling for both conditions. 1, 2

Rationale for Discontinuing Buspirone

• Buspirone is not an effective treatment for major depressive disorder and lacks FDA approval for this indication; it is approved only for generalized anxiety disorder. 2
• Buspirone has shown no efficacy for smoking cessation, with studies reporting abstinence rates ranging from 16% to 89% in placebo groups versus 36% to 88% in buspirone groups—essentially no difference. 3
• The current dose of 7.5 mg daily is subtherapeutic even for anxiety (typical dosing is 15-60 mg/day), suggesting the patient is receiving no meaningful benefit from this medication. 3

Bupropion as the Optimal Single Agent

Bupropion uniquely addresses both depression and smoking cessation simultaneously, making it the ideal choice for this patient with dual diagnoses. 1, 2

Dosing Protocol for Combined Indication

• Start bupropion SR 150 mg once daily in the morning for days 1-3, then increase to 150 mg twice daily (total 300 mg/day) if tolerated. 1, 2, 4
• Begin bupropion 1-2 weeks before the target quit date to establish therapeutic drug levels before attempting cessation. 1, 2, 4
• The second dose must be taken before 3 PM to minimize insomnia risk, as bupropion has activating properties. 2
• Maximum dose is 300 mg/day for smoking cessation to maintain seizure risk at approximately 0.1% (1 in 1,000). 1, 2, 4

Expected Efficacy

• For smoking cessation: bupropion increases 12-month abstinence by approximately 9-10 percentage points compared to placebo (~19% quit rate versus 11% with placebo). 2, 4
• For depression: bupropion achieves remission rates of 42-49%, equivalent to SSRIs but with significantly lower rates of sexual dysfunction and weight gain. 2
• Bupropion may be particularly beneficial for patients with comorbid depression and nicotine dependence, addressing both conditions through complementary noradrenergic/dopaminergic mechanisms. 1, 4

Critical Safety Screening Before Prescribing Bupropion

Absolute Contraindications (Must Rule Out)

• History of seizure disorder or any condition predisposing to seizures (prior head trauma, brain tumor, stroke, brain metastases). 1, 5, 6
• Current or past eating disorder (anorexia nervosa or bulimia), as these markedly increase seizure risk. 1, 6
• Current use of MAOIs or within 14 days of MAOI discontinuation (including linezolid). 1, 6
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs, which lowers seizure threshold. 1, 6
• Uncontrolled hypertension, as bupropion can elevate blood pressure and heart rate. 1, 2

Special Monitoring for Young Adults

• All patients younger than 24 years carry an FDA black-box warning for increased risk of suicidal thoughts and behaviors during the first 1-2 months of antidepressant therapy. 2, 6
• Assess for suicidal ideation, agitation, irritability, or unusual behavioral changes during weeks 1-2 after starting bupropion, as this is the highest-risk period. 2, 6
• Schedule follow-up within 1-2 weeks of initiation, then weekly during the first month to monitor for neuropsychiatric adverse effects. 2

Behavioral Support Requirements

Pharmacotherapy alone is insufficient—combining bupropion with behavioral counseling significantly improves outcomes for both depression and smoking cessation. 1, 4

Structured Counseling Protocol

• Provide a minimum of 4 counseling sessions totaling 91-300 minutes of contact to maximize pharmacotherapy effectiveness. 4
• Set a definite quit date within 1-2 weeks of the first consultation, emphasizing complete abstinence as the goal. 1
• Schedule weekly follow-up sessions for at least 4 weeks after the quit date, then monthly through 6 months. 1, 5
• Include problem-solving skills training for high-risk smoking situations and social support strategies. 1, 5
• Verify abstinence by measuring expired carbon monoxide at each visit. 1

Referral Options

• Refer to a smoking cessation quitline (1-800-QUIT-NOW) in addition to brief counseling if intensive face-to-face intervention is unavailable. 1
• Consider referral to a specialist smoking cessation clinic if available, especially if the patient has failed previous quit attempts. 1

Treatment Duration and Efficacy Assessment

• Continue bupropion for 7-12 weeks after the quit date as the initial treatment course. 1, 2, 4
• Assess efficacy formally after this 7-12 week period before deciding whether to extend therapy. 1, 4
• Nicotine withdrawal symptoms typically peak within 1-2 weeks of quitting and then subside—encourage continued therapy through brief slips during this period. 1
• For depression, allow 6-8 weeks at therapeutic doses before determining treatment response, as full antidepressant effects take this long to emerge. 2

If Initial Treatment Fails

• If the patient continues to smoke or relapses, resume or continue bupropion rather than immediately switching agents. 1
• Consider adding combination NRT (21 mg patch + short-acting NRT for cravings) to bupropion, as this combination shows the highest abstinence rates (35.5% at 12 months versus 30.3% with bupropion alone). 2, 4
• If depression symptoms persist after 6-8 weeks, augment bupropion with an SSRI (such as sertraline or escitalopram) rather than switching, as augmentation strategies show superior efficacy. 2

Alternative Strategies If Bupropion Is Contraindicated

If the patient has any absolute contraindication to bupropion (especially seizure history), use combination NRT plus an SSRI to address both smoking cessation and depression safely. 5

Combination NRT Protocol

• 21 mg nicotine patch daily plus short-acting NRT (gum, lozenge, or nasal spray) for cravings, continued for 12 weeks minimum. 1, 5
• Combination NRT carries zero seizure risk and has no psychiatric contraindications, making it the safest option for complex patients. 5
• Blood nicotine levels from NRT are significantly lower than from smoking, and nicotine toxicity is rare even with combination therapy. 1, 5

Varenicline as Alternative

• Varenicline 0.5 mg once daily for days 1-3, then 0.5 mg twice daily for days 4-7, then 1 mg twice daily for weeks 2-12 achieves 2-3 fold higher cessation rates than bupropion. 1, 5
• Varenicline does not increase seizure risk (contraindicated only in patients with brain metastases) and may be equally effective in patients with baseline depressive symptoms. 5, 7
• Monitor for nausea (common side effect) and neuropsychiatric symptoms, though the high-quality EAGLES trial (n=8,144) found no significant increase in neuropsychiatric adverse events compared to placebo. 1, 2

Common Pitfalls to Avoid

• Do not continue buspirone, as it provides no benefit for either depression or smoking cessation and delays effective treatment. 3
• Do not skip the 1-2 week lead-in period before the quit date, as therapeutic bupropion levels must be established for optimal efficacy. 2, 4
• Do not exceed 300 mg/day total bupropion dose for smoking cessation, as seizure risk increases markedly above this threshold. 1, 2, 4
• Do not neglect intensive monitoring during weeks 1-2 in this 22-year-old patient, as the suicide risk is highest during the initial treatment period in young adults. 2, 6
• Do not rely on pharmacotherapy alone—behavioral support is essential and increases cessation rates from 18% to 21%. 4
• Do not assume bupropion will work immediately for depression—allow the full 6-8 weeks before declaring treatment failure. 2

Monitoring Parameters

• Blood pressure and heart rate at baseline and periodically during the first 12 weeks, as bupropion can cause modest elevations. 2, 4
• Suicidal ideation, agitation, and behavioral changes weekly during the first month, especially critical in patients under 24 years. 2, 6
• Smoking status and expired CO levels at each visit to verify abstinence and provide accountability. 1
• Depressive symptoms at 6-8 weeks to assess antidepressant response and determine if augmentation is needed. 2