What SSRI (selective serotonin reuptake inhibitor) can be combined with Wellbutrin SR (bupropion) 150mg bid (twice daily) in a patient taking aspirin?

SSRI Selection with Wellbutrin SR and Aspirin

Sertraline or citalopram/escitalopram are the preferred SSRIs to combine with bupropion (Wellbutrin SR) 150mg BID in a patient taking aspirin, with sertraline having the most favorable drug interaction profile and citalopram/escitalopram having the least effect on cytochrome P450 enzymes.

Primary Considerations

Bleeding Risk Management

The combination of SSRIs with aspirin increases bleeding risk, particularly gastrointestinal bleeding 1. When selecting an SSRI for a patient already on aspirin:

• All SSRIs carry increased bleeding risk when combined with aspirin or NSAIDs, with rare events including ecchymosis, hematoma, epistaxis, petechiae, and hemorrhage 1
• Monitor closely for signs of abnormal bleeding, especially gastrointestinal symptoms 1
• The bleeding risk is a class effect and cannot be entirely avoided, but SSRI selection can minimize additional drug interaction complications 1

Drug Interaction Profile

Sertraline is the optimal first choice because:

• Compared with other SSRIs, sertraline has less effect on metabolism of other medications 1
• Well tolerated with established efficacy 1, 2
• Lower potential for drug interactions compared to paroxetine, fluoxetine, and fluvoxamine 2

Citalopram/escitalopram are excellent alternatives because:

• They have the least effect on CYP450 isoenzymes compared with other SSRIs 1
• Lower propensity for drug interactions 1
• Caution: Citalopram may prolong QT interval at doses exceeding 40 mg/day and should be avoided in patients with long QT syndrome 1

Serotonin Syndrome Risk

When combining bupropion with an SSRI, serotonin syndrome risk exists but is manageable 1:

• Start the SSRI at a low dose and increase slowly 1
• Monitor closely in the first 24-48 hours after starting or dose changes 1
• Symptoms include mental status changes, neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia) 1
• Bupropion can inhibit CYP2D6, potentially increasing SSRI blood levels 3

SSRIs to Avoid or Use with Caution

Paroxetine should be avoided or used cautiously:

• More anticholinergic than other SSRIs 1
• Associated with increased risk of suicidal thinking compared to other SSRIs 1
• Higher potential for drug interactions via CYP2D6 1
• Associated with discontinuation syndrome 1

Fluvoxamine should be avoided:

• Greatest potential for drug-drug interactions among SSRIs 1
• Interacts with multiple CYP450 enzymes (CYP1A2, CYP2C19, CYP2C9, CYP3A4, CYP2D6) 1

Fluoxetine requires caution:

• Very long half-life may complicate side effect management 1
• Significant CYP2D6 interactions 1

Practical Prescribing Algorithm

Starting Regimen

For Sertraline:

• Start 25-50 mg daily 1
• Increase to 50-200 mg daily as tolerated 1
• Maximum dose 200 mg daily 1

For Citalopram:

• Start 10 mg daily 1
• Maximum 40 mg daily (do not exceed due to QT prolongation risk) 1

For Escitalopram:

• Start 10 mg daily 4
• Maximum 20 mg daily 4

Monitoring Requirements

• Bleeding surveillance: Educate patient about signs of bleeding (bruising, nosebleeds, GI symptoms) 1
• Serotonin syndrome monitoring: Especially in first month and after dose increases 1
• Behavioral activation: Monitor for agitation, restlessness, insomnia in early treatment 1
• Suicidality: Close monitoring especially in first months and after dosage adjustments 1

Clinical Pearls

• The combination of escitalopram and bupropion-SR has demonstrated good efficacy (50% remission rate) and tolerability in clinical trials 4
• Bupropion itself does not significantly increase bleeding risk compared to SSRIs 5
• Consider slower titration to minimize serotonin syndrome risk when combining serotonergic agents 1
• Discontinuation syndrome is more common with paroxetine, fluvoxamine, and sertraline; taper when discontinuing 1