Combining Wellbutrin (Bupropion) with Cipralex (Escitalopram)
Yes, an adult patient with no significant medical history can safely take Wellbutrin (bupropion) with Cipralex (escitalopram), as this combination is a recognized and effective treatment strategy for depression with a favorable safety profile. 1
Evidence Supporting Safety and Efficacy
The American College of Physicians explicitly recognizes bupropion augmentation of SSRIs as a standard treatment approach, with moderate-quality evidence showing that discontinuation due to adverse events was actually lower with bupropion (12.5%) compared to buspirone (20.6%, p<0.001) when used as augmentation therapy. 1
This combination leverages complementary mechanisms of action: escitalopram selectively inhibits serotonin reuptake while bupropion affects dopaminergic and noradrenergic systems, providing synergistic antidepressant effects without overlapping side effect profiles. 1
Clinical trial data demonstrates superior outcomes with combination therapy: an open-label study of escitalopram plus bupropion-SR achieved 62% response rates and 50% remission rates in patients with chronic or recurrent depression, substantially higher than typical SSRI monotherapy results (approximately 30%). 2
Key Clinical Advantages
Bupropion counteracts SSRI-induced sexual dysfunction, which is a common reason for treatment discontinuation with escitalopram alone, as bupropion has the lowest rate of sexual side effects among antidepressants. 3, 1
The combination is generally well-tolerated: in the pivotal study, only 6% of patients discontinued due to side effects, with a low overall burden of treatment-emergent adverse events. 2
Both medications can be safely co-administered without a washout period, as there are no contraindicated pharmacokinetic interactions between these agents. 4
Critical Safety Monitoring Requirements
Monitor for seizure risk, particularly with bupropion: both medications can potentially lower the seizure threshold, though this is primarily a concern with bupropion at doses above 400 mg/day. Bupropion is contraindicated in patients with seizure disorders, eating disorders, or abrupt discontinuation of alcohol/benzodiazepines. 1
Watch for serotonin syndrome during the initial weeks: although the risk is theoretical given bupropion's minimal serotonergic activity, monitor for tremor, diarrhea, delirium, neuromuscular rigidity, and hyperthermia, especially during dose titration. 4
Assess for suicidal ideation during the first 1-2 months, as the risk for suicide attempts is greatest during the initial treatment period and after medication changes. 5
Recommended Dosing Strategy
Start escitalopram at 10 mg daily, then add bupropion-SR 150 mg daily after one week to establish tolerability of the SSRI first. 2
Titrate escitalopram to a maximum of 20 mg daily (do not exceed this dose due to QT prolongation risk). 5, 2
Increase bupropion-SR gradually to 300-400 mg daily based on response and tolerability, typically achieving target doses by weeks 6-8. 2
Absolute Contraindications
Never combine either medication with MAOIs due to risk of hypertensive crisis or serotonin syndrome; allow at least 14 days washout when switching to/from MAOIs. 1
Avoid bupropion in patients with seizure history, eating disorders, or conditions that increase seizure risk (stroke, brain metastases, abrupt alcohol/benzodiazepine withdrawal). 1
Common Pitfalls to Avoid
Do not add bupropion before optimizing escitalopram dose and duration: ensure the patient has been on escitalopram 20 mg for at least 6-8 weeks before declaring monotherapy inadequate and adding augmentation. 5, 1
Do not exceed escitalopram 20 mg daily, as higher doses increase cardiac risk without additional therapeutic benefit. 5
Do not dismiss the combination due to theoretical concerns about polypharmacy: the evidence clearly supports this as a first-line augmentation strategy with superior efficacy and tolerability compared to alternatives. 1, 6