What is the recommended method to transition a patient from bupropion 150 mg to fluoxetine 20 mg?

Switching from Wellbutrin 150mg to Prozac 20mg

You can stop Wellbutrin 150mg and start Prozac 20mg immediately the next day—no washout period is required because neither drug is an MAOI. 1

Immediate Transition Protocol

Day 1 of Switch

• Stop bupropion 150mg completely and begin fluoxetine 20mg the following morning 1
• No tapering of bupropion is necessary at this dose, though some clinicians prefer a gradual taper to minimize potential withdrawal symptoms 1
• The immediate switch is safe because there are no significant pharmacokinetic interactions between these medications 1

Critical Pre-Switch Safety Screening

Before initiating fluoxetine, confirm the patient has NOT taken:

• MAOIs within the past 14 days—concurrent use can precipitate serotonin syndrome within 24-48 hours 1
• Other serotonergic agents (tramadol, meperidine, methadone, fentanyl, dextromethorphan, St. John's wort) that increase serotonin syndrome risk 1

Monitoring During the First 2 Weeks

Week 1-2 monitoring is critical because:

• The risk of suicide attempts is highest during the first 1-2 months of antidepressant therapy, especially in patients under 24 years 1
• Watch for early signs of serotonin syndrome: mental-status changes (confusion, agitation), neuromuscular hyperactivity (tremor, clonus), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 1
• Assess for suicidal ideation, agitation, irritability, or unusual behavioral changes 1

Expected Timeline for Response

• Full therapeutic assessment should occur at 6-8 weeks after starting fluoxetine 20mg 1
• If no adequate response by 6-8 weeks, consider dose adjustment (fluoxetine can be increased to 40-80mg daily) or alternative strategies 1, 2
• Early improvement may be seen within 1-2 weeks, but definitive response evaluation requires the full 6-8 week trial 3

Why This Switch May Be Considered

Common Reasons for Switching from Bupropion to Fluoxetine

Bupropion non-response:

• Approximately 60% of patients who fail an SSRI trial respond to bupropion, but conversely, some patients fail bupropion and respond to SSRIs 4
• Response rates to fluoxetine are comparable to bupropion (58-63% responder rates in head-to-head trials) 2

Contraindications to bupropion that fluoxetine does not share:

• Seizure disorders or conditions predisposing to seizures 1
• Uncontrolled hypertension (bupropion can elevate blood pressure) 1
• Eating disorders (bulimia/anorexia)—bupropion increases seizure risk in these conditions 1

Comorbid anxiety:

• SSRIs like fluoxetine are generally preferred first-line for anxious depression, whereas bupropion has minimal direct anxiolytic effects 1

Tolerability Trade-offs

Advantages of fluoxetine:

• Better for prominent anxiety symptoms 1
• No seizure risk elevation 1
• Does not elevate blood pressure 1

Disadvantages of fluoxetine compared to bupropion:

• Significantly higher rates of sexual dysfunction (bupropion has the lowest sexual dysfunction rates among antidepressants) 1, 3
• More likely to cause weight gain (bupropion is associated with weight loss or weight neutrality) 1, 3
• Higher rates of sedation 1

Alternative Strategy: Combination Therapy

If the goal is to augment rather than switch, adding fluoxetine 20mg to bupropion 150mg is a well-established strategy:

• Combination therapy from initiation doubles remission rates compared to monotherapy (52% remission with mirtazapine+fluoxetine vs 25% with fluoxetine alone) 5
• Augmenting SSRIs with bupropion decreases depression severity more than buspirone augmentation 1
• The combination addresses depression through complementary mechanisms (serotonergic via fluoxetine, noradrenergic/dopaminergic via bupropion) 1
• No significant pharmacokinetic interactions preclude concurrent use, though both can lower seizure threshold—adhere strictly to maximum dosing (bupropion ≤450mg/day) 1

Critical Safety Pitfalls to Avoid

• Do not skip intensive monitoring during weeks 1-2—this period carries the highest suicide risk 1
• Do not combine with MAOIs or start within 14 days of MAOI discontinuation—this applies to fluoxetine, not the bupropion-to-fluoxetine switch itself 1
• Do not assess treatment failure before 6-8 weeks at therapeutic doses unless significant adverse effects occur 1
• Screen for QT-interval prolongation risk before starting fluoxetine, as it can prolong QT at higher doses 1